Vitamin D3 in Systemic Lupus Erythematosus

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT00710021
• Collaborator: Autoimmunity Centers of Excellence (Other)
• Enrollment: 57
• Locations: 8
• Arms: 3
• Duration (Months): 31.9
• Patients Per Site: 7.1
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The purpose of this study is to explore the impact of vitamin D3 on the expression of alpha interferon (IFN alpha) expression in systemic lupus erythematosus (SLE) patients with vitamin D deficiency.

Condition or Disease	Intervention/Treatment	Phase
Systemic Lupus Erythematosus; SLE; Lupus	Drug: Vitamin D3; Drug: Vitamin D3 placebo	Phase 2

Detailed Description

Systemic Lupus Erythematosus (SLE) is an autoimmune disease characterized by the production of autoantibodies with subsequent immune complex deposition and tissue inflammation. The role of interferon (IFN) alpha in the development of SLE has been repeatedly documented. Vitamin D deficiency is common among lupus patients. Vitamin D is recognized as a regulator of immune response. This study will explore the impact of vitamin D3 supplementation on IFN alpha expression in SLE patients.

The study will last approximately 12 weeks and consist of three treatment groups: 1.) Participants will receive vitamin D3 2000 IU daily 2.) Participants will receive vitamin D3 4000 IU daily 3.) Participants will receive a vitamin D3 placebo daily. There will be four study visits for each participant. Visits will occur at screening, study entry, and Weeks 6 and 12. Physical examination, vital signs, and blood and urine tests will occur at all visits. For females of childbearing potential, a pregnancy test will be performed at screening and Week 6.

Study Design

• Study Type: Interventional
• Actual Enrollment: 57 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Effect of Vitamin D3 on the IFN Alpha Signature in Patients With Systemic Lupus Erythematosus (ALE02)
• Study Start Date: Nov 1, 2008
• Actual Primary Completion Date: Jul 1, 2011
• Actual Study Completion Date: Jul 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: vitamin D3 2000 IU Participants in this arm take a vitamin D3 dose of 2000 international units (IU) daily by mouth for a duration of 12 weeks.	Drug: Vitamin D3; 8% vitamin D3 powder, 84% microcrystalline cellulose, 8% fumed silica by weight; Other Names: Cholecalciferol
Experimental: vitamin D3 4000 IU Participants in this arm take a vitamin D3 dose of 4000 international units (IU) daily by mouth for a duration of 12 weeks.	Drug: Vitamin D3; 8% vitamin D3 powder, 84% microcrystalline cellulose, 8% fumed silica by weight; Other Names: Cholecalciferol
Placebo Comparator: vitamin D3 placebo Participants in this arm take a vitamin D3 placebo daily by mouth for a duration of 12 weeks.	Drug: Vitamin D3 placebo; 86% microcrystalline cellulose, 14% fumed silica by weight; Other Names: Cholecalciferol placebo

Outcome Measures

Primary Outcome Measures

1. Percent of Participants With an IFN Alpha Signature Response at Week 12 [0, Week 12]

   Presence of an Interferon (IFN) Alpha signature response is defined as: a reduction in expression from baseline (Screening) of at least 50% for 1 of 3 IFN Alpha responsive genes (Ifit1, Ifi44, Mx1) with concurrent expression in the remaining 2 genes at a level not more than 25% above baseline, or a reduction in expression from baseline of at least 25% for 2 of the 3 IFN Alpha responsive genes with concurrent expression in the third gene at a level of no more than 25% above baseline. Gene expression was measured on peripheral blood samples using qRT-PCR. Missing data were considered as response failures during calculation.

Secondary Outcome Measures

1. Percent of Participants With an IFN Alpha Signature Response at Week 6 [0, Week 6]

   Presence of an Interferon (IFN) Alpha signature response is defined as: a reduction in expression from baseline (Screening) of at least 50% for 1 of 3 IFN Alpha responsive genes (Ifit1, Ifi44, Mx1) with concurrent expression in the remaining 2 genes at a level not more than 25% above baseline, or a reduction in expression from baseline of at least 25% for 2 of the 3 IFN Alpha responsive genes with concurrent expression in the third gene at a level of no more than 25% above baseline. Gene expression was measured on peripheral blood samples using qRT-PCR. Missing data were considered as response failures during calculation.

2. Percent of Participants With IFN Alpha Signature at Week 12 [0, Week 12]

   An Interferon (IFN) Alpha signature is defined as: expression of Mx1, Ifit1, or Ifi44 at a level greater than or equal to 4 standard deviations above the mean of a set of normal controls, or expression of 2 of the 3 genes at a level greater than or equal to 2 standard deviations above the mean of a set of normal controls. Gene expression was measured on peripheral blood samples using qRT-PCR. Missing data were assumed as signatures during calculation.

3. Percent of Participants With IFN Alpha Signature at Week 6 [Week 6]

   An Interferon (IFN) Alpha signature is defined as: expression of Mx1, Ifit1, or Ifi44 at a level greater than or equal to 4 standard deviations above the mean of a set of normal controls, or expression of 2 of the 3 genes at a level greater than or equal to 2 standard deviations above the mean of a set of normal controls. Gene expression was measured on peripheral blood samples using qRT-PCR. Missing data were assumed as signatures during calculation.

4. qRT-PCR Fold Change in Ifit1 Gene Expression From Baseline to Week 12 [0, Week 12]

   The Ifit1 gene is one of three genes included in the definition of the alpha-interferon signature used for this study. This gene encodes an interferon-induced protein with tetratricopeptide repeats. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to measure gene expression in peripheral blood mononuclear cells obtained by blood draw. Gene expression is quantified as "fold change" relative to normal controls and is computed using a comparative CT (threshold cycle) method. A study hypothesis was that expression of alpha-interferon signature genes would decrease with increasing vitamin D levels. A decrease in gene expression from baseline to Week 12 is represented as a negative value (and vice versa).

5. qRT-PCR Fold Change in Ifit1 Gene Expression From Baseline to Week 6 [0, Week 6]

   The Ifit1 gene is one of three genes included in the definition of the alpha-interferon signature used for this study. It encodes an interferon-induced protein with tetratricopeptide repeats. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to measure gene expression in peripheral blood mononuclear cells obtained by blood draw. Gene expression is quantified as "fold change" relative to normal controls and is computed using a comparative CT (threshold cycle) method. A study hypothesis was that expression of alpha-interferon signature genes would decrease with increasing vitamin D levels. A decrease in gene expression from baseline to Week 6 is represented as a negative value (and vice versa).

6. qRT-PCR Fold Change in Ifi44 Gene Expression From Baseline to Week 12 [0, Week 12]

   The Ifi44 gene is one of three genes included in the definition of the alpha-interferon signature used for this study. It encodes interferon-induced protein 44. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to measure gene expression in peripheral blood mononuclear cells obtained by blood draw. Gene expression is quantified as "fold change" relative to normal controls and is computed using a comparative CT (threshold cycle) method. A study hypothesis was that expression of alpha-interferon signature genes would decrease with increasing vitamin D levels. A decrease in gene expression from baseline to Week 12 is represented as a negative value (and vice versa).

7. qRT-PCR Fold Change in Ifi44 Gene Expression From Baseline to Week 6 [0, Week 6]

   The Ifi44 gene is one of three genes included in the definition of the alpha-interferon signature used for this study. It encodes interferon-induced protein 44. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to measure gene expression in peripheral blood mononuclear cells obtained by blood draw. Gene expression is quantified as "fold change" relative to normal controls and is computed using a comparative CT (threshold cycle) method. A study hypothesis was that expression of alpha-interferon signature genes would decrease with increasing vitamin D levels. A decrease in gene expression from baseline to Week 6 is represented as a negative value (and vice versa).

8. qRT-PCR Fold Change in Mx1 Gene Expression From Baseline to Week 12 [0, Week 12]

   The Mx1 gene is one of three genes included in the definition of the alpha-interferon signature used for this study. It encodes for the homolog of mouse myxovirus (influenza virus) resistance 1 protein. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to measure gene expression in peripheral blood mononuclear cells obtained by blood draw. Gene expression is quantified as "fold change" relative to normal controls and is computed using a comparative CT (threshold cycle) method. A study hypothesis was that expression of alpha-interferon signature genes would decrease with increasing vitamin D levels. A decrease in gene expression from baseline to Week 12 is represented as a negative value (and vice versa).

9. qRT-PCR Fold Change in Mx1 Gene Expression From Baseline to Week 6 [0, Week 6]

   The Mx1 gene is one of three genes included in the definition of the alpha-interferon signature used for this study. It encodes for the homolog of mouse myxovirus (influenza virus) resistance 1 protein. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to measure gene expression in peripheral blood mononuclear cells obtained by blood draw. Gene expression is quantified as "fold change" relative to normal controls and is computed using a comparative CT (threshold cycle) method. A study hypothesis was that expression of alpha-interferon signature genes would decrease with increasing vitamin D levels. A decrease in gene expression from baseline to Week 6 is represented as a negative value (and vice versa).

10. Change in Serum C3 Level From Baseline to Week 12 [0, Week 12]

    C3 is a blood test that measures the activity of the complement component 3 (C3) protein. The normal C3 range is 75 to 135 mg/dL. Patients with active systemic lupus erythematosus may have a lower-than-normal level of C3. A decrease in C3 level over time may indicate disease activity. An increase in C3 from baseline to Week 12 is represented as a positive value (and vice versa).

11. Change in Serum C3 Level From Baseline to Week 6 [0, Week 6]

    C3 is a blood test that measures the activity of the complement component 3 (C3) protein. The normal C3 range is 75 to 135 mg/dL. Patients with active systemic lupus erythematosus may have a lower-than-normal level of C3. A decrease in C3 level over time may indicate disease activity. An increase in C3 from baseline to Week 6 is represented as a positive value (and vice versa).

12. Change in Serum C4 Level From Baseline to Week 12 [0, Week 12]

    C4 is a blood test that measures the activity of the complement component 4 (C4) protein. The normal range for males is 12 to 72 mg/dL and the normal range for females is 13 to 75 mg/dL. Patients with active systemic lupus erythematosus may have a lower-than-normal level of C4. A decrease in C4 level over time may indicate disease activity. An increase in C4 from baseline to Week 12 is represented as a positive value (and vice versa).

13. Change in Serum C4 Level From Baseline to Week 6 [0, Week 6]

    Outcome measure description: C4 is a blood test that measures the activity of the complement component 4 (C4) protein. The normal range for males is 12 to 72 mg/dL and the normal range for females is 13 to 75 mg/dL. Patients with active systemic lupus erythematosus may have a lower-than-normal level of C4. A decrease in C4 level over time may indicate disease activity. An increase in C4 from baseline to Week 6 is represented as a positive value (and vice versa).

14. Change in Status for Anti-double-stranded DNA Autoantibody From Baseline to Week 12 [0, Week 12]

    Patients with systemic lupus erythematosus (SLE) may have autoantibodies (e.g., self against self) to double-stranded DNA. Double-stranded DNA is one of multiple diagnostic tests for SLE and levels may be associated with disease activity. A positive test for autoantibodies to double-stranded DNA is based on the normal range from the local laboratory. Change in status (+ or -) from baseline is evaluated.

15. Change in Status for Anti-double-stranded DNA Autoantibody From Baseline to Week 6 [0, Week 6]

    Patients with systemic lupus erythematosus (SLE) may have autoantibodies (e.g., self against self) to double-stranded DNA. Double-stranded DNA is one of multiple diagnostic tests for SLE and levels may be associated with disease activity. A positive test for autoantibodies to double-stranded DNA is based on the normal range from the local laboratory. Change in status (+ or -) from baseline is evaluated.

16. Change in SELENA-SLEDAI Total Score From Baseline to Week 12 [0, Week 12]

    The modified Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus (SLE) Disease Activity Index (SELENA-SLEDAI) score is a weighted scale score ranging from 0 to 105 based on the presence or absence of 24 manifestations of SLE. The SELENA-SLEDAI assesses disease activity for 10 days prior to and including the day of assessment. For this study, the SELENA-SLEDAI score was modified to include proteinuria defined by dipstick rather than 24 hour urine. Positive change in the SELENA-SLEDAI score indicate increased disease activity.

17. Cardiorespiratory BILAG Status at Week 12 [Week 12]

    The British Isles Lupus Assessment Group (BILAG) assessment gives a grade for each of 9 body systems (e.g., domains). Grades reflect systemic lupus erythematosus disease activity as follows: A (severe), B (moderate), C (mild), D (inactive at present but previously affected), E (inactive and system never involved). To be randomized, subjects had to have mild or inactive disease (C,D,E) in all but the mucocutaneous system in which B(moderate) disease was also allowed. The percent of subjects experiencing A or B level activity at Week 12 is assessed for the "Cardiorespiratory-specific" body system.

18. Constitutional BILAG Status at Week 12 [Week 12]

    The British Isles Lupus Assessment Group (BILAG) assessment gives a grade for each of 9 body systems (e.g., domains). Grades reflect systemic lupus erythematosus disease activity as follows: A (severe), B (moderate), C (mild), D (inactive at present but previously affected), E (inactive and system never involved). To be randomized, subjects had to have mild or inactive disease (C,D,E) in all but the mucocutaneous system in which B(moderate) disease was also allowed. The percent of subjects experiencing A or B level activity at Week 12 is assessed for the "Constitutional-specific" body system.

19. Gastrointestinal BILAG Status at Week 12 [Week 12]

    The British Isles Lupus Assessment Group (BILAG) assessment gives a grade for each of 9 body systems (e.g., domains). Grades reflect systemic lupus erythematosus disease activity as follows: A (severe), B (moderate), C (mild), D (inactive at present but previously affected), E (inactive and system never involved). To be randomized, subjects had to have mild or inactive disease (C,D,E) in all but the mucocutaneous system in which B(moderate) disease was also allowed. The percent of subjects experiencing A or B level activity at Week 12 is assessed for the "Gastrointestinal-specific" body system.

20. Hematological BILAG Status at Week 12 [Week 12]

    The British Isles Lupus Assessment Group (BILAG) assessment gives a grade for each of 9 body systems (e.g., domains). Grades reflect systemic lupus erythematosus disease activity as follows: A (severe), B (moderate), C (mild), D (inactive at present but previously affected), E (inactive and system never involved). To be randomized, subjects had to have mild or inactive disease (C,D,E) in all but the mucocutaneous system in which B(moderate) disease was also allowed. The percent of subjects experiencing A or B level activity at Week 12 is assessed for the "Hematological-specific" body system.

21. Mucocutaneous BILAG Status at Week 12 [Week 12]

    The British Isles Lupus Assessment Group (BILAG) assessment gives a grade for each of 9 body systems (e.g., domains). Grades reflect systemic lupus erythematosus disease activity as follows: A (severe), B (moderate), C (mild), D (inactive at present but previously affected), E (inactive and system never involved). To be randomized, subjects had to have mild or inactive disease (C,D,E) in all but the mucocutaneous system in which B(moderate) disease was also allowed. The percent of subjects experiencing A or B level activity at Week 12 is assessed for the "Mucocutaneous-specific" body system.

22. Musculoskeletal BILAG Status at Week 12 [Week 12]

    Outcome measure description: The British Isles Lupus Assessment Group (BILAG) assessment gives a grade for each of 9 body systems (e.g., domains). Grades reflect systemic lupus erythematosus disease activity as follows: A (severe), B (moderate), C (mild), D (inactive at present but previously affected), E (inactive and system never involved). To be randomized, subjects had to have mild or inactive disease (C,D,E) in all but the mucocutaneous system in which B(moderate) disease was also allowed. The percent of subjects experiencing A or B level activity at Week 12 is assessed for the "Musculoskeletal-specific" body system.

23. Neuropsychiatric BILAG Status at Week 12 [Week 12]

    The British Isles Lupus Assessment Group (BILAG) assessment gives a grade for each of 9 body systems (e.g., domains). Grades reflect systemic lupus erythematosus disease activity as follows: A (severe), B (moderate), C (mild), D (inactive at present but previously affected), E (inactive and system never involved). To be randomized, subjects had to have mild or inactive disease (C,D,E) in all but the mucocutaneous system in which B(moderate) disease was also allowed. The percent of subjects experiencing A or B level activity at Week 12 is assessed for the "Neuropsychiatric-specific" body system.

24. Ophthalmic BILAG Status at Week 12 [Week 12]

    The British Isles Lupus Assessment Group (BILAG) assessment gives a grade for each of 9 body systems (e.g., domains). Grades reflect systemic lupus erythematosus disease activity as follows: A (severe), B (moderate), C (mild), D (inactive at present but previously affected), E (inactive and system never involved). To be randomized, subjects had to have mild or inactive disease (C,D,E) in all but the mucocutaneous system in which B(moderate) disease was also allowed. The percent of subjects experiencing A or B level activity at Week 12 is assessed for the "Ophthalmic-specific" body system.

25. Renal BILAG Status at Week 12 [Week 12]

    The British Isles Lupus Assessment Group (BILAG) assessment gives a grade for each of 9 body systems (e.g., domains). Grades reflect systemic lupus erythematosus disease activity as follows: A (severe), B (moderate), C (mild), D (inactive at present but previously affected), E (inactive and system never involved). To be randomized, subjects had to have mild or inactive disease (C,D,E) in all but the mucocutaneous system in which B(moderate) disease was also allowed. The percent of subjects experiencing A or B level activity at Week 12 is assessed for the "Renal-specific" body system.

26. Percent of Participants With Adverse Events of Grade 3 or Above [From start of study treatment through Week 12]

    Grades are based on National Cancer Institute--Common Terminology Criteria (NCI-CTCAE) Version 3.0 over the duration of the study. Participants who experienced at least one grade 3 or higher adverse event (AE) are counted only once. The adverse events are treatment-emergent, which means that the AE occurred after taking the first dose of study drug.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Diagnosis of SLE by American College of Rheumatology (ACR) criteria

• Serum 25-OH vitamin D level of 20 ng/mL or less

• Stable disease at screening, defined as a modified Safety of Estrogens in Lupus Erythematosus National Assessment SLE Disease Activity Index (SELENA-SLEDAI) of 4 or less

• Interferon (IFN) signature present. More information about this criterion can be found in the protocol

• Positive anti-double-stranded (anti-ds) DNA antibody blood test at screening

• If on corticosteroids, the dose must be less than 20 mg per day and stable for 4 weeks prior to screening and at study entry

• If on immunosuppressive or immunomodulatory medication such as azathioprine, methotrexate, leflunomide, mycophenolate, or hydroxychloroquine, the dose must be stable for 3 months prior to screening and at study entry

• If receiving a multivitamin or a vitamin D supplement, the dose of vitamin D must be 800 IU daily or less and stable for the 3 months prior to screening and at study entry

• Agree to use effective contraceptive methods for the duration of the study

Exclusion Criteria:

• Unwilling to stop using drugs or substances that may interfere with fat absorption

• Hypercalcemia

• Hypercalciuria

• History of hyperparathyroidism

• History of kidney stones

• History of cancer, except cervical carcinoma in situ and resected basal and squamous cell carcinomas of the skin

• Known history of chronic viral infections, including human immunodeficiency virus (HIV), Hepatitis B, and Hepatitis C

• Known active tuberculosis

• Any British Isles Lupus Assessment Group (BILAG) A or B manifestation with the exception of a BILAG B mucocutaneous manifestation

• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) liver function tests greater than or equal to two times the upper limit of normal

• Dialysis or serum creatinine greater than 1.5 mg/dL

• Expectation by the investigator to increase corticosteroid or immunosuppressive or immunomodulatory medication dose at screening, study entry, or over the course of the study

• Treatment with cyclophosphamide within 3 months of screening

• Treatment with rituximab within 12 months of screening

• Other investigational drug and or treatment during the 4 weeks or seven half lives of the other investigational drug prior to study entry

• Drug or alcohol abuse within 6 months prior to study entry

• Treatment with digoxin

• Treatment with teriparatide

• Any condition that, in the opinion of the investigator, would jeopardize the subject's safety following exposure to the study drug

• Pregnant or breastfeeding

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama	Birmingham	Alabama	United States	35294
2	University of California, San Francisco	San Francisco	California	United States	94143
3	Brigham and Women's Hospital	Boston	Massachusetts	United States	02115
4	Feinstein Institute for Medical Research	Manhassett	New York	United States	11030
5	University of Rochester	Rochester	New York	United States	14642
6	Duke University Medical Center	Durham	North Carolina	United States	27710
7	University of Pittsburgh	Pittsburgh	Pennsylvania	United States	15261
8	Medical University of South Carolina	Charleston	South Carolina	United States	29425

Sponsors and Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID)
• Autoimmunity Centers of Excellence

Investigators

• Study Chair: Cynthia Aranow, MD, The Feinstein Institute for Medical Research
• Study Chair: Diane Kamen, MD, Medical University of South Carolina

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• National Institute of Allergy and Infectious Diseases (NIAID) website
• Autoimmunity Centers of Excellence (ACE) website
• National Institute of Arthritis and Musculoskeletal and Skin Diseases: Handout on Health-System Lupus Erythematosus

Publications

• Hochberg MC. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum. 1997 Sep;40(9):1725.
• Isenberg DA, Rahman A, Allen E, Farewell V, Akil M, Bruce IN, D'Cruz D, Griffiths B, Khamashta M, Maddison P, McHugh N, Snaith M, Teh LS, Yee CS, Zoma A, Gordon C. BILAG 2004. Development and initial validation of an updated version of the British Isles Lupus Assessment Group's disease activity index for patients with systemic lupus erythematosus. Rheumatology (Oxford). 2005 Jul;44(7):902-6. Epub 2005 Apr 6.
• Kamen DL, Cooper GS, Bouali H, Shaftman SR, Hollis BW, Gilkeson GS. Vitamin D deficiency in systemic lupus erythematosus. Autoimmun Rev. 2006 Feb;5(2):114-7. Epub 2005 Jun 21. Review.
• Mangini AJ, Lafyatis R, Van Seventer JM. Type I interferons inhibition of inflammatory T helper cell responses in systemic lupus erythematosus. Ann N Y Acad Sci. 2007 Jun;1108:11-23. Review.
• Tan EM, Cohen AS, Fries JF, Masi AT, McShane DJ, Rothfield NF, Schaller JG, Talal N, Winchester RJ. The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum. 1982 Nov;25(11):1271-7.

• Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
• ClinicalTrials.gov Identifier: NCT00710021
• Other Study ID Numbers: DAIT ALE02
• First Posted: Jul 3, 2008
• Last Update Posted: Apr 26, 2017
• Last Verified: Mar 1, 2017

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID): Systemic lupus erythematosus; SLE; Vitamin D3; Vitamin D deficiency; IFN alpha expression
• Additional relevant MeSH terms: Lupus Erythematosus, Systemic; Vitamin D; Ergocalciferols; Cholecalciferol; Vitamins

Study Results

Participant Flow

Arm/Group Title	Placebo	Vitamin D3 2000 IU	Vitamin D3 4000 IU
Arm/Group Description	Participants received a 12-week course of oral vitamin D3-placebo (cholecalciferol placebo, 1 dose daily).	Participants received a 12-week course of oral Vitamin D3 (cholecalciferol, 2,000 international units [IU] daily).	Participants received a 12-week course of oral vitamin D3 (cholecalciferol, 4,000 IU daily).
Period Title: Overall Study
STARTED	19	19	19
Modified Intent-to-Treat (mITT)	19	17	18
COMPLETED	18	16	18
NOT COMPLETED	1	3	1

Baseline Characteristics

Arm/Group Title	Placebo	Vitamin D3 2000 IU	Vitamin D3 4000 IU	Total
Arm/Group Description	Participants received a 12-week course of oral vitamin D3-placebo (cholecalciferol placebo, 1 dose daily).	Participants received a 12-week course of oral Vitamin D3 (cholecalciferol, 2,000 international units [IU] daily).	Participants received a 12-week course of oral vitamin D3 (cholecalciferol, 4,000 IU daily).	Total of all reporting groups
Overall Participants	19	17	18	54
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	38.7 (12.3)	36.5 (10.9)	38.3 (12.9)	37.9 (11.9)
Sex: Female, Male (Count of Participants)
Female	18 94.7%	17 100%	16 88.9%	51 94.4%
Male	1 5.3%	0 0%	2 11.1%	3 5.6%
Region of Enrollment (participants) [Number]
United States	19 100%	17 100%	18 100%	54 100%
Years with Systemic Lupus Erythematosus (SLE) at Baseline (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	10.9 (7.8)	10.0 (7.8)	8.7 (6.0)	9.9 (7.1)
Number of American College of Rheumatology (ACR) Criteria met at Screening (number of criteria met) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [number of criteria met]	5.4 (1.3)	5.5 (1.1)	5.8 (1.3)	5.6 (1.2)
Modified SELENA-SLEDAI Score (score) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [score]	2.9 (1.2)	2.7 (1.2)	2.6 (1.0)	2.7 (1.1)

Outcome Measures

1. Primary Outcome

Title	Percent of Participants With an IFN Alpha Signature Response at Week 12
Description	Presence of an Interferon (IFN) Alpha signature response is defined as: a reduction in expression from baseline (Screening) of at least 50% for 1 of 3 IFN Alpha responsive genes (Ifit1, Ifi44, Mx1) with concurrent expression in the remaining 2 genes at a level not more than 25% above baseline, or a reduction in expression from baseline of at least 25% for 2 of the 3 IFN Alpha responsive genes with concurrent expression in the third gene at a level of no more than 25% above baseline. Gene expression was measured on peripheral blood samples using qRT-PCR. Missing data were considered as response failures during calculation.
Time Frame	0, Week 12

Outcome Measure Data

Analysis Population Description

Modified Intent-to-Treat. Although presence of a positive IFN Alpha Signature at the Screening visit was an entry criterion for the study, 8 subjects (4 Placebo, 2 Vitamin D3 2000 IU, 2 Vitamin D3 4000 IU ) who did not have a signature were included in the study.

Arm/Group Title	Placebo	Vitamin D3 2000 IU	Vitamin D3 4000 IU	Vitamin D3 2000 and 4000 IU (Pooled )
Arm/Group Description	Participants received a 12-week course of oral vitamin D3-placebo (cholecalciferol placebo, 1 dose daily).	Participants received a 12-week course of oral Vitamin D3 (cholecalciferol, 2,000 international units [IU] daily).	Participants received a 12-week course of oral vitamin D3 (cholecalciferol, 4,000 IU daily).	This is a statistically pooled group of those participants randomized to either vitamin D3 2,000 IU or vitamin D3 4,000 IU treatment (e.g., pooled group for statistical analysis purposes only).
Measure Participants	19	17	18	35
Number [Percent of participants]	36.8 193.7%	23.5 138.2%	27.8 154.4%	25.7 47.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Vitamin D3 2000 and 4000 IU (Pooled )
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.53
	Comments	The p-value compares the Placebo with the pooled Vitamin D treatment group.
	Method	Fisher Exact
	Comments

2. Secondary Outcome

Title	Percent of Participants With an IFN Alpha Signature Response at Week 6
Description	Presence of an Interferon (IFN) Alpha signature response is defined as: a reduction in expression from baseline (Screening) of at least 50% for 1 of 3 IFN Alpha responsive genes (Ifit1, Ifi44, Mx1) with concurrent expression in the remaining 2 genes at a level not more than 25% above baseline, or a reduction in expression from baseline of at least 25% for 2 of the 3 IFN Alpha responsive genes with concurrent expression in the third gene at a level of no more than 25% above baseline. Gene expression was measured on peripheral blood samples using qRT-PCR. Missing data were considered as response failures during calculation.
Time Frame	0, Week 6

Outcome Measure Data

Analysis Population Description

Modified Intent-to-Treat. Although presence of a positive IFN Alpha Signature at the Screening visit was an entry criterion for the study, 8 subjects (4 Placebo, 2 Vitamin D3 2000 IU, 2 Vitamin D3 4000 IU ) who did not have a signature were included in the study.

Arm/Group Title	Placebo	Vitamin D3 2000 IU	Vitamin D3 4000 IU	Vitamin D3 2000 and 4000 IU (Pooled )
Arm/Group Description	Participants received a 12-week course of oral vitamin D3-placebo (cholecalciferol placebo, 1 dose daily).	Participants received a 12-week course of oral Vitamin D3 (cholecalciferol, 2,000 international units [IU] daily).	Participants received a 12-week course of oral vitamin D3 (cholecalciferol, 4,000 IU daily).	This is a statistically pooled group of those participants randomized to either vitamin D3 2,000 IU or vitamin D3 4,000 IU treatment (e.g., pooled group for statistical analysis purposes only).
Measure Participants	19	17	18	35
Number [Percent of participants]	36.8 193.7%	17.6 103.5%	5.6 31.1%	11.4 21.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Vitamin D3 2000 and 4000 IU (Pooled )
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.038
	Comments	The p-value compares the Placebo with the pooled Vitamin D treatment group.
	Method	Fisher Exact
	Comments

3. Secondary Outcome

Title	Percent of Participants With IFN Alpha Signature at Week 12
Description	An Interferon (IFN) Alpha signature is defined as: expression of Mx1, Ifit1, or Ifi44 at a level greater than or equal to 4 standard deviations above the mean of a set of normal controls, or expression of 2 of the 3 genes at a level greater than or equal to 2 standard deviations above the mean of a set of normal controls. Gene expression was measured on peripheral blood samples using qRT-PCR. Missing data were assumed as signatures during calculation.
Time Frame	0, Week 12

Outcome Measure Data

Analysis Population Description

Modified Intent-to-Treat. Although presence of a positive IFN Alpha Signature at the Screening visit was an entry criterion for the study, 8 subjects (4 Placebo, 2 Vitamin D3 2000 IU, 2 Vitamin D3 4000 IU) who did not have a signature were included in the study.

Arm/Group Title	Placebo	Vitamin D3 2000 IU	Vitamin D3 4000 IU	Vitamin D3 2000 and 4000 IU (Pooled )
Arm/Group Description	Participants received a 12-week course of oral vitamin D3-placebo (cholecalciferol placebo, 1 dose daily).	Participants received a 12-week course of oral Vitamin D3 (cholecalciferol, 2,000 international units [IU] daily).	Participants received a 12-week course of oral vitamin D3 (cholecalciferol, 4,000 IU daily).	This is a statistically pooled group of those participants randomized to either vitamin D3 2,000 IU or vitamin D3 4,000 IU treatment (e.g., pooled group for statistical analysis purposes only).
Measure Participants	19	17	18	35
Number [Percent of participants]	78.9 415.3%	94.1 553.5%	100.0 555.6%	97.1 179.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Vitamin D3 2000 and 4000 IU (Pooled )
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.047
	Comments	The p-value compares the Placebo with the pooled Vitamin D treatment group.
	Method	Fisher Exact
	Comments

4. Secondary Outcome

Title	Percent of Participants With IFN Alpha Signature at Week 6
Description	An Interferon (IFN) Alpha signature is defined as: expression of Mx1, Ifit1, or Ifi44 at a level greater than or equal to 4 standard deviations above the mean of a set of normal controls, or expression of 2 of the 3 genes at a level greater than or equal to 2 standard deviations above the mean of a set of normal controls. Gene expression was measured on peripheral blood samples using qRT-PCR. Missing data were assumed as signatures during calculation.
Time Frame	Week 6

Outcome Measure Data

Analysis Population Description

Modified Intent-to-Treat. Although presence of a positive IFN Alpha Signature at the Screening visit was an entry criterion for the study, 8 subjects (4 Placebo, 2 Vitamin D3 2000 IU, 2 Vitamin D3 4000 IU) who did not have a signature were included in the study.

Arm/Group Title	Placebo	Vitamin D3 2000 IU	Vitamin D3 4000 IU	Vitamin D3 2000 and 4000 IU (Pooled )
Arm/Group Description	Participants received a 12-week course of oral vitamin D3-placebo (cholecalciferol placebo, 1 dose daily).	Participants received a 12-week course of oral Vitamin D3 (cholecalciferol, 2,000 international units [IU] daily).	Participants received a 12-week course of oral vitamin D3 (cholecalciferol, 4,000 IU daily).	This is a statistically pooled group of those participants randomized to either vitamin D3 2,000 IU or vitamin D3 4,000 IU treatment (e.g., pooled group for statistical analysis purposes only).
Measure Participants	19	17	18	35
Number [Percent of participants]	84.2 443.2%	94.1 553.5%	100.0 555.6%	97.1 179.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Vitamin D3 2000 and 4000 IU (Pooled )
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.12
	Comments	The p-value compares the Placebo with the pooled Vitamin D treatment group.
	Method	Fisher Exact
	Comments

5. Secondary Outcome

Title	qRT-PCR Fold Change in Ifit1 Gene Expression From Baseline to Week 12
Description	The Ifit1 gene is one of three genes included in the definition of the alpha-interferon signature used for this study. This gene encodes an interferon-induced protein with tetratricopeptide repeats. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to measure gene expression in peripheral blood mononuclear cells obtained by blood draw. Gene expression is quantified as "fold change" relative to normal controls and is computed using a comparative CT (threshold cycle) method. A study hypothesis was that expression of alpha-interferon signature genes would decrease with increasing vitamin D levels. A decrease in gene expression from baseline to Week 12 is represented as a negative value (and vice versa).
Time Frame	0, Week 12

Outcome Measure Data

Analysis Population Description

Modified Intent-to-Treat with available data

Arm/Group Title	Placebo	Vitamin D3 2000 IU	Vitamin D3 4000 IU	Vitamin D3 2000 and 4000 IU (Pooled )
Arm/Group Description	Participants received a 12-week course of oral vitamin D3-placebo (cholecalciferol placebo, 1 dose daily).	Participants received a 12-week course of oral Vitamin D3 (cholecalciferol, 2,000 international units [IU] daily).	Participants received a 12-week course of oral vitamin D3 (cholecalciferol, 4,000 IU daily).	This is a statistically pooled group of those participants randomized to either vitamin D3 2,000 IU or vitamin D3 4,000 IU treatment (e.g., pooled group for statistical analysis purposes only).
Measure Participants	15	15	18	33
Mean (Standard Deviation) [qRT-PCR fold change]	-8.6 (40.5)	-2.9 (57.0)	5.2 (33.9)	1.5 (45.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Vitamin D3 2000 and 4000 IU (Pooled )
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.31
	Comments	The p-value compares the Placebo with the pooled Vitamin D treatment group.
	Method	F-tests derived from the GLM
	Comments	The test was for the comparison of pooled Vitamin D versus Placebo after adjustment for baseline Ifit1 expression.

6. Secondary Outcome

Title	qRT-PCR Fold Change in Ifit1 Gene Expression From Baseline to Week 6
Description	The Ifit1 gene is one of three genes included in the definition of the alpha-interferon signature used for this study. It encodes an interferon-induced protein with tetratricopeptide repeats. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to measure gene expression in peripheral blood mononuclear cells obtained by blood draw. Gene expression is quantified as "fold change" relative to normal controls and is computed using a comparative CT (threshold cycle) method. A study hypothesis was that expression of alpha-interferon signature genes would decrease with increasing vitamin D levels. A decrease in gene expression from baseline to Week 6 is represented as a negative value (and vice versa).
Time Frame	0, Week 6

Outcome Measure Data

Analysis Population Description

Modified Intent-to-Treat with available data

Arm/Group Title	Placebo	Vitamin D3 2000 IU	Vitamin D3 4000 IU	Vitamin D3 2000 and 4000 IU (Pooled )
Arm/Group Description	Participants received a 12-week course of oral vitamin D3-placebo (cholecalciferol placebo, 1 dose daily).	Participants received a 12-week course of oral Vitamin D3 (cholecalciferol, 2,000 international units [IU] daily).	Participants received a 12-week course of oral vitamin D3 (cholecalciferol, 4,000 IU daily).	This is a statistically pooled group of those participants randomized to either vitamin D3 2,000 IU or vitamin D3 4,000 IU treatment (e.g., pooled group for statistical analysis purposes only).
Measure Participants	16	13	17	30
Mean (Standard Deviation) [qRT-PCR fold change]	-15.5 (38.0)	-11.6 (35.5)	6.3 (18.1)	-1.4 (28.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Vitamin D3 2000 and 4000 IU (Pooled )
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.019
	Comments	The p-value compares the Placebo with the pooled Vitamin D treatment group.
	Method	F-tests derived from the GLM
	Comments	The test was for the comparison of pooled Vitamin D versus Placebo after adjustment for baseline Ifit1 expression.

7. Secondary Outcome

Title	qRT-PCR Fold Change in Ifi44 Gene Expression From Baseline to Week 12
Description	The Ifi44 gene is one of three genes included in the definition of the alpha-interferon signature used for this study. It encodes interferon-induced protein 44. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to measure gene expression in peripheral blood mononuclear cells obtained by blood draw. Gene expression is quantified as "fold change" relative to normal controls and is computed using a comparative CT (threshold cycle) method. A study hypothesis was that expression of alpha-interferon signature genes would decrease with increasing vitamin D levels. A decrease in gene expression from baseline to Week 12 is represented as a negative value (and vice versa).
Time Frame	0, Week 12

Outcome Measure Data

Analysis Population Description

Modified Intent-to-Treat with available data

Arm/Group Title	Placebo	Vitamin D3 2000 IU	Vitamin D3 4000 IU	Vitamin D3 2000 and 4000 IU (Pooled )
Arm/Group Description	Participants received a 12-week course of oral vitamin D3-placebo (cholecalciferol placebo, 1 dose daily).	Participants received a 12-week course of oral Vitamin D3 (cholecalciferol, 2,000 international units [IU] daily).	Participants received a 12-week course of oral vitamin D3 (cholecalciferol, 4,000 IU daily).	This is a statistically pooled group of those participants randomized to either vitamin D3 2,000 IU or vitamin D3 4,000 IU treatment (e.g., pooled group for statistical analysis purposes only).
Measure Participants	15	15	18	33
Mean (Standard Deviation) [qRT-PCR fold change]	-2.5 (16.4)	-0.3 (9.8)	2.9 (11.7)	1.4 (10.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Vitamin D3 2000 and 4000 IU (Pooled )
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.28
	Comments	The p-value compares the Placebo with the pooled Vitamin D treatment group.
	Method	F-tests derived from the GLM
	Comments	The test was for the comparison of pooled Vitamin D versus Placebo after adjustment for baseline Ifi44 expression.

8. Secondary Outcome

Title	qRT-PCR Fold Change in Ifi44 Gene Expression From Baseline to Week 6
Description	The Ifi44 gene is one of three genes included in the definition of the alpha-interferon signature used for this study. It encodes interferon-induced protein 44. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to measure gene expression in peripheral blood mononuclear cells obtained by blood draw. Gene expression is quantified as "fold change" relative to normal controls and is computed using a comparative CT (threshold cycle) method. A study hypothesis was that expression of alpha-interferon signature genes would decrease with increasing vitamin D levels. A decrease in gene expression from baseline to Week 6 is represented as a negative value (and vice versa).
Time Frame	0, Week 6

Outcome Measure Data

Analysis Population Description

Modified Intent-to-Treat with available data

Arm/Group Title	Placebo	Vitamin D3 2000 IU	Vitamin D3 4000 IU	Vitamin D3 2000 and 4000 IU (Pooled )
Arm/Group Description	Participants received a 12-week course of oral vitamin D3-placebo (cholecalciferol placebo, 1 dose daily).	Participants received a 12-week course of oral Vitamin D3 (cholecalciferol, 2,000 international units [IU] daily).	Participants received a 12-week course of oral vitamin D3 (cholecalciferol, 4,000 IU daily).	This is a statistically pooled group of those participants randomized to either vitamin D3 2,000 IU or vitamin D3 4,000 IU treatment (e.g., pooled group for statistical analysis purposes only).
Measure Participants	16	13	17	30
Mean (Standard Deviation) [qRT-PCR fold change]	-3.9 (12.8)	-4.6 (11.0)	4.1 (5.9)	0.3 (9.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Vitamin D3 2000 and 4000 IU (Pooled )
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.050
	Comments	The p-value compares the Placebo with the pooled Vitamin D treatment group.
	Method	F-tests derived from the GLM
	Comments	The test was for the comparison of pooled Vitamin D versus Placebo after adjustment for baseline Ifi44 expression.

9. Secondary Outcome

Title	qRT-PCR Fold Change in Mx1 Gene Expression From Baseline to Week 12
Description	The Mx1 gene is one of three genes included in the definition of the alpha-interferon signature used for this study. It encodes for the homolog of mouse myxovirus (influenza virus) resistance 1 protein. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to measure gene expression in peripheral blood mononuclear cells obtained by blood draw. Gene expression is quantified as "fold change" relative to normal controls and is computed using a comparative CT (threshold cycle) method. A study hypothesis was that expression of alpha-interferon signature genes would decrease with increasing vitamin D levels. A decrease in gene expression from baseline to Week 12 is represented as a negative value (and vice versa).
Time Frame	0, Week 12

Outcome Measure Data

Analysis Population Description

Modified Intent-to-Treat with available data

Arm/Group Title	Placebo	Vitamin D3 2000 IU	Vitamin D3 4000 IU	Vitamin D3 2000 and 4000 IU (Pooled )
Arm/Group Description	Participants received a 12-week course of oral vitamin D3-placebo (cholecalciferol placebo, 1 dose daily).	Participants received a 12-week course of oral Vitamin D3 (cholecalciferol, 2,000 international units [IU] daily).	Participants received a 12-week course of oral vitamin D3 (cholecalciferol, 4,000 IU daily).	This is a statistically pooled group of those participants randomized to either vitamin D3 2,000 IU or vitamin D3 4,000 IU treatment (e.g., pooled group for statistical analysis purposes only).
Measure Participants	15	15	18	33
Mean (Standard Deviation) [qRT-PCR fold change]	-1.6 (14.0)	2.0 (12.5)	4.8 (11.6)	3.5 (11.9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Vitamin D3 2000 and 4000 IU (Pooled )
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.29
	Comments	The p-value compares the Placebo with the pooled Vitamin D treatment group.
	Method	F-tests derived from the GLM
	Comments	The test was for the comparison of pooled Vitamin D versus Placebo after adjustment for baseline Mx1 expression.

10. Secondary Outcome

Title	qRT-PCR Fold Change in Mx1 Gene Expression From Baseline to Week 6
Description	The Mx1 gene is one of three genes included in the definition of the alpha-interferon signature used for this study. It encodes for the homolog of mouse myxovirus (influenza virus) resistance 1 protein. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to measure gene expression in peripheral blood mononuclear cells obtained by blood draw. Gene expression is quantified as "fold change" relative to normal controls and is computed using a comparative CT (threshold cycle) method. A study hypothesis was that expression of alpha-interferon signature genes would decrease with increasing vitamin D levels. A decrease in gene expression from baseline to Week 6 is represented as a negative value (and vice versa).
Time Frame	0, Week 6

Outcome Measure Data

Analysis Population Description

Modified Intent-to-Treat with available data

Arm/Group Title	Placebo	Vitamin D3 2000 IU	Vitamin D3 4000 IU	Vitamin D3 2000 and 4000 IU (Pooled )
Arm/Group Description	Participants received a 12-week course of oral vitamin D3-placebo (cholecalciferol placebo, 1 dose daily).	Participants received a 12-week course of oral Vitamin D3 (cholecalciferol, 2,000 international units [IU] daily).	Participants received a 12-week course of oral vitamin D3 (cholecalciferol, 4,000 IU daily).	This is a statistically pooled group of those participants randomized to either vitamin D3 2,000 IU or vitamin D3 4,000 IU treatment (e.g., pooled group for statistical analysis purposes only).
Measure Participants	16	13	17	30
Mean (Standard Deviation) [qRT-PCR fold change]	-4.8 (10.5)	1.4 (19.5)	0.7 (6.7)	1.0 (13.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Vitamin D3 2000 and 4000 IU (Pooled )
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.014
	Comments	The p-value compares the Placebo with the pooled Vitamin D treatment group.
	Method	F-tests derived from the GLM
	Comments	The test was for the comparison of pooled Vitamin D versus Placebo after adjustment for baseline Mx1 expression.

11. Secondary Outcome

Title	Change in Serum C3 Level From Baseline to Week 12
Description	C3 is a blood test that measures the activity of the complement component 3 (C3) protein. The normal C3 range is 75 to 135 mg/dL. Patients with active systemic lupus erythematosus may have a lower-than-normal level of C3. A decrease in C3 level over time may indicate disease activity. An increase in C3 from baseline to Week 12 is represented as a positive value (and vice versa).
Time Frame	0, Week 12

Outcome Measure Data

Analysis Population Description

Modified Intent-to-Treat with available data

Arm/Group Title	Placebo	Vitamin D3 2000 IU	Vitamin D3 4000 IU	Vitamin D3 2000 and 4000 IU (Pooled )
Arm/Group Description	Participants received a 12-week course of oral vitamin D3-placebo (cholecalciferol placebo, 1 dose daily).	Participants received a 12-week course of oral Vitamin D3 (cholecalciferol, 2,000 international units [IU] daily).	Participants received a 12-week course of oral vitamin D3 (cholecalciferol, 4,000 IU daily).	This is a statistically pooled group of those participants randomized to either vitamin D3 2,000 IU or vitamin D3 4,000 IU treatment (e.g., pooled group for statistical analysis purposes only).
Measure Participants	18	16	18	34
Mean (Standard Deviation) [mg/dL]	1.8 (16.1)	0.7 (11.1)	2.9 (11.1)	1.9 (11.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Vitamin D3 2000 and 4000 IU (Pooled )
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.96
	Comments	The p-value compares the Placebo with the pooled Vitamin D treatment group.
	Method	F-tests derived from the GLM
	Comments	The test was for the comparison of pooled Vitamin D versus Placebo after adjustment for baseline serum C3 level.

12. Secondary Outcome

Title	Change in Serum C3 Level From Baseline to Week 6
Description	C3 is a blood test that measures the activity of the complement component 3 (C3) protein. The normal C3 range is 75 to 135 mg/dL. Patients with active systemic lupus erythematosus may have a lower-than-normal level of C3. A decrease in C3 level over time may indicate disease activity. An increase in C3 from baseline to Week 6 is represented as a positive value (and vice versa).
Time Frame	0, Week 6

Outcome Measure Data

Analysis Population Description

Modified Intent-to-Treat with available data

Arm/Group Title	Placebo	Vitamin D3 2000 IU	Vitamin D3 4000 IU	Vitamin D3 2000 and 4000 IU (Pooled )
Arm/Group Description	Participants received a 12-week course of oral vitamin D3-placebo (cholecalciferol placebo, 1 dose daily).	Participants received a 12-week course of oral Vitamin D3 (cholecalciferol, 2,000 international units [IU] daily).	Participants received a 12-week course of oral vitamin D3 (cholecalciferol, 4,000 IU daily).	This is a statistically pooled group of those participants randomized to either vitamin D3 2,000 IU or vitamin D3 4,000 IU treatment (e.g., pooled group for statistical analysis purposes only).
Measure Participants	19	15	18	33
Mean (Standard Deviation) [mg/dL]	3.3 (10.9)	3.8 (11.2)	3.7 (10.3)	3.8 (10.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Vitamin D3 2000 and 4000 IU (Pooled )
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.67
	Comments	The p-value compares the Placebo with the pooled Vitamin D treatment group.
	Method	F-tests derived from the GLM
	Comments	The test was for the comparison of pooled Vitamin D versus Placebo after adjustment for baseline serum C3 level.

13. Secondary Outcome

Title	Change in Serum C4 Level From Baseline to Week 12
Description	C4 is a blood test that measures the activity of the complement component 4 (C4) protein. The normal range for males is 12 to 72 mg/dL and the normal range for females is 13 to 75 mg/dL. Patients with active systemic lupus erythematosus may have a lower-than-normal level of C4. A decrease in C4 level over time may indicate disease activity. An increase in C4 from baseline to Week 12 is represented as a positive value (and vice versa).
Time Frame	0, Week 12

Outcome Measure Data

Analysis Population Description

Modified Intent-to-Treat with available data

Arm/Group Title	Placebo	Vitamin D3 2000 IU	Vitamin D3 4000 IU	Vitamin D3 2000 and 4000 IU (Pooled )
Arm/Group Description	Participants received a 12-week course of oral vitamin D3-placebo (cholecalciferol placebo, 1 dose daily).	Participants received a 12-week course of oral Vitamin D3 (cholecalciferol, 2,000 international units [IU] daily).	Participants received a 12-week course of oral vitamin D3 (cholecalciferol, 4,000 IU daily).	This is a statistically pooled group of those participants randomized to either vitamin D3 2,000 IU or vitamin D3 4,000 IU treatment (e.g., pooled group for statistical analysis purposes only).
Measure Participants	18	16	18	34
Mean (Standard Deviation) [mg/dL]	0.2 (2.5)	-0.3 (2.9)	1.9 (4.4)	.9 (3.9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Vitamin D3 2000 and 4000 IU (Pooled )
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.59
	Comments	The p-value compares the Placebo with the pooled Vitamin D treatment group.
	Method	F-tests derived from the GLM
	Comments	The test was for the comparison of pooled Vitamin D versus Placebo after adjustment for baseline serum C4 level.

14. Secondary Outcome

Title	Change in Serum C4 Level From Baseline to Week 6
Description	Outcome measure description: C4 is a blood test that measures the activity of the complement component 4 (C4) protein. The normal range for males is 12 to 72 mg/dL and the normal range for females is 13 to 75 mg/dL. Patients with active systemic lupus erythematosus may have a lower-than-normal level of C4. A decrease in C4 level over time may indicate disease activity. An increase in C4 from baseline to Week 6 is represented as a positive value (and vice versa).
Time Frame	0, Week 6

Outcome Measure Data

Analysis Population Description

Modified Intent-to-Treat with available data

Arm/Group Title	Placebo	Vitamin D3 2000 IU	Vitamin D3 4000 IU	Vitamin D3 2000 and 4000 IU (Pooled )
Arm/Group Description	Participants received a 12-week course of oral vitamin D3-placebo (cholecalciferol placebo, 1 dose daily).	Participants received a 12-week course of oral Vitamin D3 (cholecalciferol, 2,000 international units [IU] daily).	Participants received a 12-week course of oral vitamin D3 (cholecalciferol, 4,000 IU daily).	This is a statistically pooled group of those participants randomized to either vitamin D3 2,000 IU or vitamin D3 4,000 IU treatment (e.g., pooled group for statistical analysis purposes only).
Measure Participants	19	15	18	33
Mean (Standard Deviation) [mg/dL]	0.3 (3.3)	-0.8 (2.7)	0.4 (2.8)	-0.2 (2.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Vitamin D3 2000 and 4000 IU (Pooled )
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.65
	Comments	The p-value compares the Placebo with the pooled Vitamin D treatment group.
	Method	F-tests derived from the GLM
	Comments	The test was for the comparison of pooled Vitamin D versus Placebo after adjustment for baseline serum C4 level.

15. Secondary Outcome

Title	Change in Status for Anti-double-stranded DNA Autoantibody From Baseline to Week 12
Description	Patients with systemic lupus erythematosus (SLE) may have autoantibodies (e.g., self against self) to double-stranded DNA. Double-stranded DNA is one of multiple diagnostic tests for SLE and levels may be associated with disease activity. A positive test for autoantibodies to double-stranded DNA is based on the normal range from the local laboratory. Change in status (+ or -) from baseline is evaluated.
Time Frame	0, Week 12

Outcome Measure Data

Analysis Population Description

Modified Intent-to-Treat with available data

Arm/Group Title	Placebo	Vitamin D3 2000 IU	Vitamin D3 4000 IU	Vitamin D3 2000 and 4000 IU (Pooled )
Arm/Group Description	Participants received a 12-week course of oral vitamin D3-placebo (cholecalciferol placebo, 1 dose daily).	Participants received a 12-week course of oral Vitamin D3 (cholecalciferol, 2,000 international units [IU] daily).	Participants received a 12-week course of oral vitamin D3 (cholecalciferol, 4,000 IU daily).	This is a statistically pooled group of those participants randomized to either vitamin D3 2,000 IU or vitamin D3 4,000 IU treatment (e.g., pooled group for statistical analysis purposes only).
Measure Participants	17	16	18	34
Positive at Baseline, Positive at Week 12	94.1 495.3%	100.0 588.2%	77.8 432.2%	88.2 163.3%
Positive at Baseline, Negative at Week 12	0.0 0%	0.0 0%	11.0 61.1%	6.0 11.1%
Negative at Baseline, Positive at Week 12	0.0 0%	0.0 0%	5.6 31.1%	2.9 5.4%
Negative at Baseline, Negative at Week 12	5.9 31.1%	0.0 0%	5.6 31.1%	2.9 5.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Vitamin D3 2000 and 4000 IU (Pooled )
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.86
	Comments	The p-value compares the Placebo with the pooled Vitamin D treatment group.
	Method	Fisher Exact
	Comments

16. Secondary Outcome

Title	Change in Status for Anti-double-stranded DNA Autoantibody From Baseline to Week 6
Description	Patients with systemic lupus erythematosus (SLE) may have autoantibodies (e.g., self against self) to double-stranded DNA. Double-stranded DNA is one of multiple diagnostic tests for SLE and levels may be associated with disease activity. A positive test for autoantibodies to double-stranded DNA is based on the normal range from the local laboratory. Change in status (+ or -) from baseline is evaluated.
Time Frame	0, Week 6

Outcome Measure Data

Analysis Population Description

Modified Intent-to-Treat with available data

Arm/Group Title	Placebo	Vitamin D3 2000 IU	Vitamin D3 4000 IU	Vitamin D3 2000 and 4000 IU (Pooled )
Arm/Group Description	Participants received a 12-week course of oral vitamin D3-placebo (cholecalciferol placebo, 1 dose daily).	Participants received a 12-week course of oral Vitamin D3 (cholecalciferol, 2,000 international units [IU] daily).	Participants received a 12-week course of oral vitamin D3 (cholecalciferol, 4,000 IU daily).	This is a statistically pooled group of those participants randomized to either vitamin D3 2,000 IU or vitamin D3 4,000 IU treatment (e.g., pooled group for statistical analysis purposes only).
Measure Participants	19	16	18	34
Positive at Baseline, Positive at Week 6	94.7 498.4%	93.7 551.2%	88.9 493.9%	91.2 168.9%
Positive at Baseline, Negative at Week 6	0.0 0%	6.3 37.1%	0.0 0%	2.9 5.4%
Negative at Baseline, Positive at Week 6	0.0 0%	0.0 0%	0.0 0%	0.0 0%
Negative at Baseline, Negative at Week 6	5.3 27.9%	0.0 0%	11.1 61.7%	5.9 10.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Vitamin D3 2000 and 4000 IU (Pooled )
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	1.0
	Comments	The p-value compares the Placebo with the pooled Vitamin D treatment group.
	Method	Fisher Exact
	Comments

17. Secondary Outcome

Title	Change in SELENA-SLEDAI Total Score From Baseline to Week 12
Description	The modified Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus (SLE) Disease Activity Index (SELENA-SLEDAI) score is a weighted scale score ranging from 0 to 105 based on the presence or absence of 24 manifestations of SLE. The SELENA-SLEDAI assesses disease activity for 10 days prior to and including the day of assessment. For this study, the SELENA-SLEDAI score was modified to include proteinuria defined by dipstick rather than 24 hour urine. Positive change in the SELENA-SLEDAI score indicate increased disease activity.
Time Frame	0, Week 12

Outcome Measure Data

Analysis Population Description

Modified Intent-to-Treat with available data

Arm/Group Title	Placebo	Vitamin D3 2000 IU	Vitamin D3 4000 IU	Vitamin D3 2000 and 4000 IU (Pooled )
Arm/Group Description	Participants received a 12-week course of oral vitamin D3-placebo (cholecalciferol placebo, 1 dose daily).	Participants received a 12-week course of oral Vitamin D3 (cholecalciferol, 2,000 international units [IU] daily).	Participants received a 12-week course of oral vitamin D3 (cholecalciferol, 4,000 IU daily).	This is a statistically pooled group of those participants randomized to either vitamin D3 2,000 IU or vitamin D3 4,000 IU treatment (e.g., pooled group for statistical analysis purposes only).
Measure Participants	18	16	18	34
Mean (Standard Deviation) [Change in Scores on a Scale]	0.0 (0.7)	0.2 (1.8)	0.2 (1.9)	0.2 (1.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Vitamin D3 2000 and 4000 IU (Pooled )
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.62
	Comments	The p-value compares the Placebo with the pooled Vitamin D treatment group.
	Method	F-tests derived from the GLM
	Comments	The test was for the comparison of pooled Vitamin D versus Placebo after adjustment for baseline SELENA-SLEDAI score.

18. Secondary Outcome

Title	Cardiorespiratory BILAG Status at Week 12
Description	The British Isles Lupus Assessment Group (BILAG) assessment gives a grade for each of 9 body systems (e.g., domains). Grades reflect systemic lupus erythematosus disease activity as follows: A (severe), B (moderate), C (mild), D (inactive at present but previously affected), E (inactive and system never involved). To be randomized, subjects had to have mild or inactive disease (C,D,E) in all but the mucocutaneous system in which B(moderate) disease was also allowed. The percent of subjects experiencing A or B level activity at Week 12 is assessed for the "Cardiorespiratory-specific" body system.
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

Modified Intent-to-Treat with available data

Arm/Group Title	Placebo	Vitamin D3 2000 IU	Vitamin D3 4000 IU	Vitamin D3 2000 and 4000 IU (Pooled )
Arm/Group Description	Participants received a 12-week course of oral vitamin D3-placebo (cholecalciferol placebo, 1 dose daily).	Participants received a 12-week course of oral Vitamin D3 (cholecalciferol, 2,000 international units [IU] daily).	Participants received a 12-week course of oral vitamin D3 (cholecalciferol, 4,000 IU daily).	This is a statistically pooled group of those participants randomized to either vitamin D3 2,000 IU or vitamin D3 4,000 IU treatment (e.g., pooled group for statistical analysis purposes only).
Measure Participants	18	16	18	34
Number [Percent with grade A or B]	0.0	6.3	0.0	2.9

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Vitamin D3 2000 and 4000 IU (Pooled )
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	1.0
	Comments	The p-value compares the Placebo with the pooled Vitamin D treatment group.
	Method	Fisher Exact
	Comments

19. Secondary Outcome

Title	Constitutional BILAG Status at Week 12
Description	The British Isles Lupus Assessment Group (BILAG) assessment gives a grade for each of 9 body systems (e.g., domains). Grades reflect systemic lupus erythematosus disease activity as follows: A (severe), B (moderate), C (mild), D (inactive at present but previously affected), E (inactive and system never involved). To be randomized, subjects had to have mild or inactive disease (C,D,E) in all but the mucocutaneous system in which B(moderate) disease was also allowed. The percent of subjects experiencing A or B level activity at Week 12 is assessed for the "Constitutional-specific" body system.
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

Modified Intent-to-Treat with available data

Arm/Group Title	Placebo	Vitamin D3 2000 IU	Vitamin D3 4000 IU	Vitamin D3 2000 and 4000 IU (Pooled )
Arm/Group Description	Participants received a 12-week course of oral vitamin D3-placebo (cholecalciferol placebo, 1 dose daily).	Participants received a 12-week course of oral Vitamin D3 (cholecalciferol, 2,000 international units [IU] daily).	Participants received a 12-week course of oral vitamin D3 (cholecalciferol, 4,000 IU daily).	This is a statistically pooled group of those participants randomized to either vitamin D3 2,000 IU or vitamin D3 4,000 IU treatment (e.g., pooled group for statistical analysis purposes only).
Measure Participants	18	16	18	34
Number [Percent with grade A or B]	0.0	0.0	0.0	0.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Vitamin D3 2000 and 4000 IU (Pooled )
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	1.0
	Comments	The p-value compares the Placebo with the pooled Vitamin D treatment group.
	Method	Fisher Exact
	Comments

20. Secondary Outcome

Title	Gastrointestinal BILAG Status at Week 12
Description	The British Isles Lupus Assessment Group (BILAG) assessment gives a grade for each of 9 body systems (e.g., domains). Grades reflect systemic lupus erythematosus disease activity as follows: A (severe), B (moderate), C (mild), D (inactive at present but previously affected), E (inactive and system never involved). To be randomized, subjects had to have mild or inactive disease (C,D,E) in all but the mucocutaneous system in which B(moderate) disease was also allowed. The percent of subjects experiencing A or B level activity at Week 12 is assessed for the "Gastrointestinal-specific" body system.
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

Modified Intent-to-Treat with available data

Arm/Group Title	Placebo	Vitamin D3 2000 IU	Vitamin D3 4000 IU	Vitamin D3 2000 and 4000 IU (Pooled )
Arm/Group Description	Participants received a 12-week course of oral vitamin D3-placebo (cholecalciferol placebo, 1 dose daily).	Participants received a 12-week course of oral Vitamin D3 (cholecalciferol, 2,000 international units [IU] daily).	Participants received a 12-week course of oral vitamin D3 (cholecalciferol, 4,000 IU daily).	This is a statistically pooled group of those participants randomized to either vitamin D3 2,000 IU or vitamin D3 4,000 IU treatment (e.g., pooled group for statistical analysis purposes only).
Measure Participants	18	16	18	34
Number [Percent with grade A or B]	0.0	0.0	0.0	0.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Vitamin D3 2000 and 4000 IU (Pooled )
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	1.0
	Comments	The p-value compares the Placebo with the pooled Vitamin D treatment group.
	Method	Fisher Exact
	Comments

21. Secondary Outcome

Title	Hematological BILAG Status at Week 12
Description	The British Isles Lupus Assessment Group (BILAG) assessment gives a grade for each of 9 body systems (e.g., domains). Grades reflect systemic lupus erythematosus disease activity as follows: A (severe), B (moderate), C (mild), D (inactive at present but previously affected), E (inactive and system never involved). To be randomized, subjects had to have mild or inactive disease (C,D,E) in all but the mucocutaneous system in which B(moderate) disease was also allowed. The percent of subjects experiencing A or B level activity at Week 12 is assessed for the "Hematological-specific" body system.
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

Modified Intent-to-Treat with available data

Arm/Group Title	Placebo	Vitamin D3 2000 IU	Vitamin D3 4000 IU	Vitamin D3 2000 and 4000 IU (Pooled )
Arm/Group Description	Participants received a 12-week course of oral vitamin D3-placebo (cholecalciferol placebo, 1 dose daily).	Participants received a 12-week course of oral Vitamin D3 (cholecalciferol, 2,000 international units [IU] daily).	Participants received a 12-week course of oral vitamin D3 (cholecalciferol, 4,000 IU daily).	This is a statistically pooled group of those participants randomized to either vitamin D3 2,000 IU or vitamin D3 4,000 IU treatment (e.g., pooled group for statistical analysis purposes only).
Measure Participants	18	16	18	34
Number [Percent with grade A or B]	0.0	0.0	0.0	0.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Vitamin D3 2000 and 4000 IU (Pooled )
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	1.0
	Comments	The p-value compares the Placebo with the pooled Vitamin D treatment group.
	Method	Fisher Exact
	Comments

22. Secondary Outcome

Title	Mucocutaneous BILAG Status at Week 12
Description	The British Isles Lupus Assessment Group (BILAG) assessment gives a grade for each of 9 body systems (e.g., domains). Grades reflect systemic lupus erythematosus disease activity as follows: A (severe), B (moderate), C (mild), D (inactive at present but previously affected), E (inactive and system never involved). To be randomized, subjects had to have mild or inactive disease (C,D,E) in all but the mucocutaneous system in which B(moderate) disease was also allowed. The percent of subjects experiencing A or B level activity at Week 12 is assessed for the "Mucocutaneous-specific" body system.
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

Modified Intent-to-Treat with available data

Arm/Group Title	Placebo	Vitamin D3 2000 IU	Vitamin D3 4000 IU	Vitamin D3 2000 and 4000 IU (Pooled )
Arm/Group Description	Participants received a 12-week course of oral vitamin D3-placebo (cholecalciferol placebo, 1 dose daily).	Participants received a 12-week course of oral Vitamin D3 (cholecalciferol, 2,000 international units [IU] daily).	Participants received a 12-week course of oral vitamin D3 (cholecalciferol, 4,000 IU daily).	This is a statistically pooled group of those participants randomized to either vitamin D3 2,000 IU or vitamin D3 4,000 IU treatment (e.g., pooled group for statistical analysis purposes only).
Measure Participants	18	16	18	34
Number [Percent with grade A or B]	5.6	12.5	0.0	5.9

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Vitamin D3 2000 and 4000 IU (Pooled )
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	1.0
	Comments	The p-value compares the Placebo with the pooled Vitamin D treatment group.
	Method	Fisher Exact
	Comments

23. Secondary Outcome

Title	Musculoskeletal BILAG Status at Week 12
Description	Outcome measure description: The British Isles Lupus Assessment Group (BILAG) assessment gives a grade for each of 9 body systems (e.g., domains). Grades reflect systemic lupus erythematosus disease activity as follows: A (severe), B (moderate), C (mild), D (inactive at present but previously affected), E (inactive and system never involved). To be randomized, subjects had to have mild or inactive disease (C,D,E) in all but the mucocutaneous system in which B(moderate) disease was also allowed. The percent of subjects experiencing A or B level activity at Week 12 is assessed for the "Musculoskeletal-specific" body system.
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

Modified Intent-to-Treat with available data

Arm/Group Title	Placebo	Vitamin D3 2000 IU	Vitamin D3 4000 IU	Vitamin D3 2000 and 4000 IU (Pooled )
Arm/Group Description	Participants received a 12-week course of oral vitamin D3-placebo (cholecalciferol placebo, 1 dose daily).	Participants received a 12-week course of oral Vitamin D3 (cholecalciferol, 2,000 international units [IU] daily).	Participants received a 12-week course of oral vitamin D3 (cholecalciferol, 4,000 IU daily).	This is a statistically pooled group of those participants randomized to either vitamin D3 2,000 IU or vitamin D3 4,000 IU treatment (e.g., pooled group for statistical analysis purposes only).
Measure Participants	18	16	18	34
Number [Percent with grade A or B]	5.6	0.0	11.1	5.9

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Vitamin D3 2000 and 4000 IU (Pooled )
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	1.0
	Comments	The p-value compares the Placebo with the pooled Vitamin D treatment group.
	Method	Fisher Exact
	Comments

24. Secondary Outcome

Title	Neuropsychiatric BILAG Status at Week 12
Description	The British Isles Lupus Assessment Group (BILAG) assessment gives a grade for each of 9 body systems (e.g., domains). Grades reflect systemic lupus erythematosus disease activity as follows: A (severe), B (moderate), C (mild), D (inactive at present but previously affected), E (inactive and system never involved). To be randomized, subjects had to have mild or inactive disease (C,D,E) in all but the mucocutaneous system in which B(moderate) disease was also allowed. The percent of subjects experiencing A or B level activity at Week 12 is assessed for the "Neuropsychiatric-specific" body system.
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

Modified Intent-to-Treat with available data

Arm/Group Title	Placebo	Vitamin D3 2000 IU	Vitamin D3 4000 IU	Vitamin D3 2000 and 4000 IU (Pooled )
Arm/Group Description	Participants received a 12-week course of oral vitamin D3-placebo (cholecalciferol placebo, 1 dose daily).	Participants received a 12-week course of oral Vitamin D3 (cholecalciferol, 2,000 international units [IU] daily).	Participants received a 12-week course of oral vitamin D3 (cholecalciferol, 4,000 IU daily).	This is a statistically pooled group of those participants randomized to either vitamin D3 2,000 IU or vitamin D3 4,000 IU treatment (e.g., pooled group for statistical analysis purposes only).
Measure Participants	18	16	18	34
Number [Percent with grade A or B]	0.0	0.0	0.0	0.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Vitamin D3 2000 and 4000 IU (Pooled )
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	1.0
	Comments	The p-value compares the Placebo with the pooled Vitamin D treatment group.
	Method	Fisher Exact
	Comments

25. Secondary Outcome

Title	Ophthalmic BILAG Status at Week 12
Description	The British Isles Lupus Assessment Group (BILAG) assessment gives a grade for each of 9 body systems (e.g., domains). Grades reflect systemic lupus erythematosus disease activity as follows: A (severe), B (moderate), C (mild), D (inactive at present but previously affected), E (inactive and system never involved). To be randomized, subjects had to have mild or inactive disease (C,D,E) in all but the mucocutaneous system in which B(moderate) disease was also allowed. The percent of subjects experiencing A or B level activity at Week 12 is assessed for the "Ophthalmic-specific" body system.
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

Modified Intent-to-Treat with available data

Arm/Group Title	Placebo	Vitamin D3 2000 IU	Vitamin D3 4000 IU	Vitamin D3 2000 and 4000 IU (Pooled )
Arm/Group Description	Participants received a 12-week course of oral vitamin D3-placebo (cholecalciferol placebo, 1 dose daily).	Participants received a 12-week course of oral Vitamin D3 (cholecalciferol, 2,000 international units [IU] daily).	Participants received a 12-week course of oral vitamin D3 (cholecalciferol, 4,000 IU daily).	This is a statistically pooled group of those participants randomized to either vitamin D3 2,000 IU or vitamin D3 4,000 IU treatment (e.g., pooled group for statistical analysis purposes only).
Measure Participants	18	16	18	34
Number [Percent with grade A or B]	0.0	0.0	0.0	0.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Vitamin D3 2000 and 4000 IU (Pooled )
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	1.0
	Comments	The p-value compares the Placebo with the pooled Vitamin D treatment group.
	Method	Fisher Exact
	Comments

26. Secondary Outcome

Title	Renal BILAG Status at Week 12
Description	The British Isles Lupus Assessment Group (BILAG) assessment gives a grade for each of 9 body systems (e.g., domains). Grades reflect systemic lupus erythematosus disease activity as follows: A (severe), B (moderate), C (mild), D (inactive at present but previously affected), E (inactive and system never involved). To be randomized, subjects had to have mild or inactive disease (C,D,E) in all but the mucocutaneous system in which B(moderate) disease was also allowed. The percent of subjects experiencing A or B level activity at Week 12 is assessed for the "Renal-specific" body system.
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

Modified Intent-to-Treat with available data

Arm/Group Title	Placebo	Vitamin D3 2000 IU	Vitamin D3 4000 IU	Vitamin D3 2000 and 4000 IU (Pooled )
Arm/Group Description	Participants received a 12-week course of oral vitamin D3-placebo (cholecalciferol placebo, 1 dose daily).	Participants received a 12-week course of oral Vitamin D3 (cholecalciferol, 2,000 international units [IU] daily).	Participants received a 12-week course of oral vitamin D3 (cholecalciferol, 4,000 IU daily).	This is a statistically pooled group of those participants randomized to either vitamin D3 2,000 IU or vitamin D3 4,000 IU treatment (e.g., pooled group for statistical analysis purposes only).
Measure Participants	18	16	18	34
Number [Percent with grade A or B]	0.0	0.0	0.0	0.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Vitamin D3 2000 and 4000 IU (Pooled )
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	1.0
	Comments	The p-value compares the Placebo with the pooled Vitamin D treatment group.
	Method	Fisher Exact
	Comments

27. Secondary Outcome

Title	Percent of Participants With Adverse Events of Grade 3 or Above
Description	Grades are based on National Cancer Institute--Common Terminology Criteria (NCI-CTCAE) Version 3.0 over the duration of the study. Participants who experienced at least one grade 3 or higher adverse event (AE) are counted only once. The adverse events are treatment-emergent, which means that the AE occurred after taking the first dose of study drug.
Time Frame	From start of study treatment through Week 12

Outcome Measure Data

Analysis Population Description

Safety

Arm/Group Title	Placebo	Vitamin D3 2000 IU	Vitamin D3 4000 IU	Vitamin D3 2000 and 4000 IU (Pooled )
Arm/Group Description	Participants received a 12-week course of oral vitamin D3-placebo (cholecalciferol placebo, 1 dose daily).	Participants received a 12-week course of oral Vitamin D3 (cholecalciferol, 2,000 international units [IU] daily).	Participants received a 12-week course of oral vitamin D3 (cholecalciferol, 4,000 IU daily).	This is a statistically pooled group of those participants randomized to either vitamin D3 2,000 IU or vitamin D3 4,000 IU treatment (e.g., pooled group for statistical analysis purposes only).
Measure Participants	19	17	18	35
Number [Percent of participants]	5.3 27.9%	23.5 138.2%	22.2 123.3%	22.9 42.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Vitamin D3 2000 and 4000 IU (Pooled )
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.10
	Comments	The p-value compares the Placebo with the pooled Vitamin D treatment group.
	Method	Cochran-Mantel-Haenszel
	Comments	Note that none of the Grade 3 or above events were considered by the investigators to be related to study treatment.

Adverse Events

Time Frame	Baseline to 12 weeks
Adverse Event Reporting Description	This study graded the severity of adverse events experienced by the study participant according to criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003)
Arm/Group Title	Placebo		Vitamin D3 2000 IU		Vitamin D3 4000 IU
Arm/Group Description	Participants received a 12-week course of oral vitamin D3-placebo (cholecalciferol placebo, 1 dose daily).		Participants received a 12-week course of oral Vitamin D3 (cholecalciferol, 2,000 international units [IU] daily).		Participants received a 12-week course of oral vitamin D3 (cholecalciferol, 4,000 IU daily).
All Cause Mortality
	Placebo		Vitamin D3 2000 IU		Vitamin D3 4000 IU
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		Vitamin D3 2000 IU		Vitamin D3 4000 IU
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/19 (0%)		0/17 (0%)		3/18 (16.7%)
Infections and infestations
Cellulitis	0/19 (0%)	0	0/17 (0%)	0	1/18 (5.6%)	1
Sinusitis	0/19 (0%)	0	0/17 (0%)	0	1/18 (5.6%)	1
Musculoskeletal and connective tissue disorders
Systemic lupus erythematosus	0/19 (0%)	0	0/17 (0%)	0	1/18 (5.6%)	1
Nervous system disorders
Cerebrovascular accident	0/19 (0%)	0	0/17 (0%)	0	1/18 (5.6%)	1
Vascular disorders
Hypertension	0/19 (0%)	0	0/17 (0%)	0	1/18 (5.6%)	1
Hypertensive emergency	0/19 (0%)	0	0/17 (0%)	0	1/18 (5.6%)	1
Other (Not Including Serious) Adverse Events
	Placebo		Vitamin D3 2000 IU		Vitamin D3 4000 IU
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	15/19 (78.9%)		16/17 (94.1%)		15/18 (83.3%)
Blood and lymphatic system disorders
Anaemia	0/19 (0%)	0	3/17 (17.6%)	3	3/18 (16.7%)	3
Lymphopenia	2/19 (10.5%)	2	1/17 (5.9%)	1	1/18 (5.6%)	1
Gastrointestinal disorders
Diarrhoea	2/19 (10.5%)	2	0/17 (0%)	0	1/18 (5.6%)	1
Infections and infestations
Upper respiratory tract infection	0/19 (0%)	0	0/17 (0%)	0	4/18 (22.2%)	4
Investigations
Blood albumin decreased	1/19 (5.3%)	1	1/17 (5.9%)	1	1/18 (5.6%)	1
Blood creatinine increased	0/19 (0%)	0	2/17 (11.8%)	2	1/18 (5.6%)	1
Blood glucose decreased	2/19 (10.5%)	2	1/17 (5.9%)	1	0/18 (0%)	0
Blood potassium decreased	4/19 (21.1%)	4	1/17 (5.9%)	1	1/18 (5.6%)	1
Haemoglobin decreased	4/19 (21.1%)	4	3/17 (17.6%)	3	5/18 (27.8%)	5
Lymphocyte count decreased	3/19 (15.8%)	3	1/17 (5.9%)	1	2/18 (11.1%)	2
Neutrophil count decreased	2/19 (10.5%)	2	3/17 (17.6%)	3	5/18 (27.8%)	5
White blood cell count decreased	6/19 (31.6%)	7	2/17 (11.8%)	2	5/18 (27.8%)	5
Metabolism and nutrition disorders
Hyperglycaemia	0/19 (0%)	0	2/17 (11.8%)	2	1/18 (5.6%)	1
Hypoalbuminaemia	1/19 (5.3%)	1	0/17 (0%)	0	3/18 (16.7%)	3
Hypoglycaemia	0/19 (0%)	0	2/17 (11.8%)	2	2/18 (11.1%)	2
Hypokalaemia	0/19 (0%)	0	2/17 (11.8%)	2	1/18 (5.6%)	1
Hyponatraemia	0/19 (0%)	0	2/17 (11.8%)	2	1/18 (5.6%)	1
Musculoskeletal and connective tissue disorders
Back pain	2/19 (10.5%)	2	0/17 (0%)	0	1/18 (5.6%)	1
Systemic lupus erythematosus	3/19 (15.8%)	3	2/17 (11.8%)	2	1/18 (5.6%)	1
Renal and urinary disorders
Lupus nephritis	1/19 (5.3%)	1	1/17 (5.9%)	1	1/18 (5.6%)	1
Skin and subcutaneous tissue disorders
Cutaneous lupus erythematosus	1/19 (5.3%)	1	1/17 (5.9%)	1	1/18 (5.6%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.