RA PLUS: Hydroxychloroquine to Improve Insulin Sensitivity in Rheumatoid Arthritis

• Sponsor: Brigham and Women's Hospital (Other)
• Overall Status: Completed
• CT.gov ID: NCT01132118
• Collaborator: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) (NIH)
• Enrollment: 30
• Location: 1
• Arms: 2
• Duration (Months): 24
• Patients Per Site Per Month: 1.2

Study Details

Study Description

Brief Summary

The purpose of this study is to determine whether hydroxychloroquine (HCQ) reduces insulin resistance in non-diabetic subjects with rheumatoid arthritis (RA). The investigators will conduct a double-blind randomized crossover trial in subjects with RA to test the hypothesis that HCQ improves insulin sensitivity. The investigators will also use data from the trial to identify determinants of insulin resistance in RA. The investigators hypothesize that RA will be associated with an increased risk of insulin resistance and that independent risk factors for increased insulin resistance in RA include higher BMI, elevated acute phase reactants, greater fat to muscle ratio, and less physical activity.

Condition or Disease	Intervention/Treatment	Phase
Rheumatoid Arthritis; Insulin Resistance	Drug: Hydroxychloroquine	Phase 3

Detailed Description

Our ability to better control the pain and disability of rheumatoid arthritis (RA) now focuses attention on reducing the impact of RA-associated comorbidities. The most common cause of death in RA is cardiovascular (CV) disease, and the risk of myocardial infarction and stroke are approximately doubled in RA. The determinants of CV risk in RA include traditional CV risk factors as well as aspects of the inflammatory process defining RA. It is likely that RA-associated inflammation accelerates atherosclerosis through direct effects on the endothelium as well as indirect effects on insulin metabolism. Several studies report an increased prevalence of insulin resistance among persons with RA. However, it is not clear whether the inflammation of RA causes insulin resistance. Corticosteroids and abnormalities in the hypothalamic-pituitary axis may also contribute to abnormal glucose metabolism. Little information is available to guide management of a pre-diabetic insulin resistance state in RA.

Hydroxychloroquine (HCQ), a commonly used medicine early in RA, may play a role in improving insulin resistance. Several previous trials demonstrated the ability of HCQ to reduce blood glucose levels in diabetics, and a large epidemiologic study found that subjects with RA using HCQ were less likely to develop diabetes. In animal models, anti-malarials lower blood glucose through slowing insulin metabolism.

With CV disease a major comorbidity in RA and insulin resistance possibly a major determinant of CV risk, intervention studies need to begin to translate prior work into clinical therapeutics.

Relevance: If this study demonstrates a beneficial effect of HCQ on insulin resistance among the randomized subjects, this would provide strong evidence that HCQ has benefits beyond RA and SLE disease activity. Currently, HCQ is stopped in many patients as they "step-up" to more aggressive DMARD treatments, or HCQ may never be tried in some patients who present with RA carrying with poor prognosis. If HCQ improves insulin sensitivity, there may be rationale for continuing HCQ chronically in patients with RA. As well, a larger clinical endpoint study would be strongly considered.

Study Design

• Study Type: Interventional
• Actual Enrollment: 30 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Hydroxychloroquine to Improve Insulin Sensitivity in Rheumatoid Arthritis
• Study Start Date: Jun 1, 2010
• Actual Primary Completion Date: Apr 1, 2012
• Actual Study Completion Date: Jun 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Other: Placebo then HCQ This arm of the study will contain half the study population after randomization. The participants in this arm will receive hydroxychloroquine for 8 weeks and then crossover to a placebo for 8 weeks. Study staff will be blinded to which order they are taking the hydroxychloroquine and placebo in.	Drug: Hydroxychloroquine; Hydroxychloroquine comes in 200 mg tablets and is taken orally. The dose provided will be based upon a calculation of 6.5 mg/kg (subject's weight), which is the dose range commonly used to treat rheumatoid arthritis and lupus. Dosages will be rounded to the nearest 100 mg.; Other Names: Plaquenil
Other: HCQ then Placebo This arm of the study will contain half the study population after randomization. The participants in this arm will receive hydroxychloroquine for 8 weeks and then crossover to a placebo for 8 weeks. Study staff will be blinded to which order they are taking the hydroxychloroquine and placebo in.	Drug: Hydroxychloroquine; Hydroxychloroquine comes in 200 mg tablets and is taken orally. The dose provided will be based upon a calculation of 6.5 mg/kg (subject's weight), which is the dose range commonly used to treat rheumatoid arthritis and lupus. Dosages will be rounded to the nearest 100 mg.; Other Names: Plaquenil

Outcome Measures

Primary Outcome Measures

1. Insulin Sensitivity Index [Baseline and Week 8]

   We will examine the effect of HCQ on the Matsuda Insulin Sensitivity Index (ISI) during the active treatment phase compared with placebo phase. ISI is based on insulin and glucose levels in a fasting state during an oral glucose tolerance test (OGTT) and is calculated as follows: ISI (Matsuda) = 10000/√ G0 X I0 X Gmean X Imean G0 - fasting plasma glucose (mg/dL) I0 - fasting plasma insulin (mIU/L) Gmean - mean plasma glucose during OGTT (mg/dL) Imean - mean plasma insulin during OGTT (mIU/L)

Secondary Outcome Measures

1. HOMA-IR [Baseline and Week 8]

   We will examine the effect of HCQ on HOMA-IR during the active treatment phase compared with placebo phase. HOMA-IR = (Glucose x insulin)/405

2. HOMA-B [Baseline and Week 8]

   HOMA-B = (360 x Insulin)/(Glucose - 63)

3. Total Cholesterol [Baseline and Week 8]

   mg/dL

4. LDL Cholesterol [Baseline and Week 8]

   mg/dL

5. HDL Cholesterol [Baseline and Week 8]

   mg/dL

6. Triglycerides [Baseline and Week 8]

   mg/dL

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Age 18 or older

• Able to provide informed consent and comply with study visits

• Hemoglobin ≥ 10 g/dL (within last two months)

• WBC ≥ 4 K/uL (within last two months)

• Platelet count ≥ 150 ≤ 450 K/uL (within last two months)

• (GFR) Creatinine clearance ≥ 70 ml/min (MDRD) (within last two months)

• SGOT, SGPT ≤ 1.5 times upper limits of normal (within last two months)

• Normal eye exam within 12 months of study entry (copy of letter from subject's ophthalmologist or optometrist stating that the subject has no evidence of macular pathology)

• Diagnosis of rheumatoid arthritis

Exclusion Criteria:

• History of any neuromuscular disease including muscular dystrophy, metabolic myopathies, peripheral neuropathy, multiple sclerosis, and other myopathies or myositides

• History of diabetes or fasting plasma glucose of 126 mg/dl or greater

• History of any untoward reaction to antimalarials

• Uncontrolled hypertension (>140/90)

• History of any ophthalmologic disease except for glaucoma or cataracts

• Planned elective surgery during the study period

• Digoxin therapy

• Treatment with corticosteroids (> 5 mg) for any disorder

• History of psoriasis

• Any chronic disease that in the opinion of the investigator warrants exclusion (e.g. inflammatory bowel disease, malignancy other than basal cell carcinoma, chronic liver disease)

• History of chronic intestinal disorders (Crohn's disease, ulcerative colitis, celiac sprue, collagenous colitis, eosinophilic enteritis)

• Creatinine clearance ≤ 60 ml/min (MDRD) (within last two months)

• Hemoglobin ≤ 10 g/dL (within last two months)

• WBC ≤ 4 K/uL (within last two months)

• Platelet count ≤ 150 ≥ 450 K/uL (within last two months)

• SGOT, SGPT ≥ 1.5 times upper limits of normal (within last two months)

• Women who are pregnant or breastfeeding

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Brigham and Women's Hospital	Boston	Massachusetts	United States	02115

Sponsors and Collaborators

• Brigham and Women's Hospital
• National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

Investigators

• Principal Investigator: Daniel H Solomon, MD, MPH, Brigham and Women's Hospital
• Principal Investigator: Elena M Massarotti, MD, Brigham and Women's Hospital
• Principal Investigator: Rajesh K Garg, MD, Brigham and Women's Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

• Chung CP, Oeser A, Solus JF, Gebretsadik T, Shintani A, Avalos I, Sokka T, Raggi P, Pincus T, Stein CM. Inflammation-associated insulin resistance: differential effects in rheumatoid arthritis and systemic lupus erythematosus define potential mechanisms. Arthritis Rheum. 2008 Jul;58(7):2105-12. doi: 10.1002/art.23600.
• Dessein PH, Joffe BI. Insulin resistance and impaired beta cell function in rheumatoid arthritis. Arthritis Rheum. 2006 Sep;54(9):2765-75.
• Emami J, Pasutto FM, Mercer JR, Jamali F. Inhibition of insulin metabolism by hydroxychloroquine and its enantiomers in cytosolic fraction of liver homogenates from healthy and diabetic rats. Life Sci. 1999;64(5):325-35.
• Gabriel SE. The epidemiology of rheumatoid arthritis. Rheum Dis Clin North Am. 2001 May;27(2):269-81. Review.
• Garcia-Webb P, Bonser AM. Insulin binding and degradation in isolated hepatocytes from streptozotocin injected rats. Biochem Biophys Res Commun. 1985 Apr 30;128(2):487-93.
• Gerstein HC, Thorpe KE, Taylor DW, Haynes RB. The effectiveness of hydroxychloroquine in patients with type 2 diabetes mellitus who are refractory to sulfonylureas--a randomized trial. Diabetes Res Clin Pract. 2002 Mar;55(3):209-19.
• Glaser K, Sung ML, O'Neill K, Belfast M, Hartman D, Carlson R, Kreft A, Kubrak D, Hsiao CL, Weichman B. Etodolac selectively inhibits human prostaglandin G/H synthase 2 (PGHS-2) versus human PGHS-1. Eur J Pharmacol. 1995 Jul 25;281(1):107-11.
• Goodson N, Marks J, Lunt M, Symmons D. Cardiovascular admissions and mortality in an inception cohort of patients with rheumatoid arthritis with onset in the 1980s and 1990s. Ann Rheum Dis. 2005 Nov;64(11):1595-601. Epub 2005 Apr 20.
• Hanley AJ, Williams K, Stern MP, Haffner SM. Homeostasis model assessment of insulin resistance in relation to the incidence of cardiovascular disease: the San Antonio Heart Study. Diabetes Care. 2002 Jul;25(7):1177-84.
• Maradit-Kremers H, Nicola PJ, Crowson CS, Ballman KV, Gabriel SE. Cardiovascular death in rheumatoid arthritis: a population-based study. Arthritis Rheum. 2005 Mar;52(3):722-32.
• Matsuda M, DeFronzo RA. Insulin sensitivity indices obtained from oral glucose tolerance testing: comparison with the euglycemic insulin clamp. Diabetes Care. 1999 Sep;22(9):1462-70.
• Quatraro A, Consoli G, Ceriello A, Giugliano D. Is there a role for chloroquine treatment in diabetes? A three case report. Diabete Metab. 1988 Sep-Oct;14(5):666-7.
• Quatraro A, Consoli G, Magno M, Caretta F, Nardozza A, Ceriello A, Giugliano D. Hydroxychloroquine in decompensated, treatment-refractory noninsulin-dependent diabetes mellitus. A new job for an old drug? Ann Intern Med. 1990 May 1;112(9):678-81.
• Reilly MP, Wolfe ML, Rhodes T, Girman C, Mehta N, Rader DJ. Measures of insulin resistance add incremental value to the clinical diagnosis of metabolic syndrome in association with coronary atherosclerosis. Circulation. 2004 Aug 17;110(7):803-9. Epub 2004 Aug 2.
• Ridker PM, Stampfer MJ, Rifai N. Novel risk factors for systemic atherosclerosis: a comparison of C-reactive protein, fibrinogen, homocysteine, lipoprotein(a), and standard cholesterol screening as predictors of peripheral arterial disease. JAMA. 2001 May 16;285(19):2481-5.
• Solomon DH, Curhan GC, Rimm EB, Cannuscio CC, Karlson EW. Cardiovascular risk factors in women with and without rheumatoid arthritis. Arthritis Rheum. 2004 Nov;50(11):3444-9.
• Solomon DH, Karlson EW, Rimm EB, Cannuscio CC, Mandl LA, Manson JE, Stampfer MJ, Curhan GC. Cardiovascular morbidity and mortality in women diagnosed with rheumatoid arthritis. Circulation. 2003 Mar 11;107(9):1303-7.
• Wasko MC, Hubert HB, Lingala VB, Elliott JR, Luggen ME, Fries JF, Ward MM. Hydroxychloroquine and risk of diabetes in patients with rheumatoid arthritis. JAMA. 2007 Jul 11;298(2):187-93.
• Young A, Koduri G, Batley M, Kulinskaya E, Gough A, Norton S, Dixey J; Early Rheumatoid Arthritis Study (ERAS) group. Mortality in rheumatoid arthritis. Increased in the early course of disease, in ischaemic heart disease and in pulmonary fibrosis. Rheumatology (Oxford). 2007 Feb;46(2):350-7. Epub 2006 Aug 14.

• Responsible Party: Daniel H. Solomon, M.D.,MPH, Director of Clinical Sciences, Brigham and Women's Hospital
• ClinicalTrials.gov Identifier: NCT01132118
• Other Study ID Numbers: 2009P001926; R21AR057924
• First Posted: May 27, 2010
• Last Update Posted: Sep 3, 2014
• Last Verified: Sep 1, 2014

• Keywords provided by Daniel H. Solomon, M.D.,MPH, Director of Clinical Sciences, Brigham and Women's Hospital: rheumatoid arthritis; insulin resistance; hydroxychloroquine; cholesterol
• Additional relevant MeSH terms: Arthritis; Arthritis, Rheumatoid; Insulin Resistance; Hydroxychloroquine

Study Results

Participant Flow

Recruitment Details	107 potentially eligible RA patients were screened during 2010-2011. 7 subjects did not meet inclusion/exclusion criteria at screening and 63 declined participation.
Pre-assignment Detail	37 subjects were initially consented, 7 withdrew consent before randomization. Thirty patients were randomized. Five patients withdrew consent after randomization and two patients stopped participation in the study due to non-serious adverse events.

Arm/Group Title	HCQ Then Placebo	Placebo Then HCQ
Arm/Group Description	This arm of the study contains half the study population after randomization. The participants in this arm received hydroxychloroquine for 8 weeks and then crossed over to a placebo for 8 weeks. Study staff was blinded to which order they were taking the hydroxychloroquine and placebo in. Hydroxychloroquine: Hydroxychloroquine comes in 200 mg tablets and is taken orally. The dose provided will be based upon a calculation of 6.5 mg/kg (subject's weight), which is the dose range commonly used to treat rheumatoid arthritis and lupus. Dosages will be rounded to the nearest 100 mg.	This arm of the study contains half the study population after randomization. The participants in this arm received hydroxychloroquine for 8 weeks and then crossed over to a placebo for 8 weeks. Study staff was blinded to which order they were taking the hydroxychloroquine and placebo in. Hydroxychloroquine: Hydroxychloroquine comes in 200 mg tablets and is taken orally. The dose provided will be based upon a calculation of 6.5 mg/kg (subject's weight), which is the dose range commonly used to treat rheumatoid arthritis and lupus. Dosages will be rounded to the nearest 100 mg.
Period Title: First Intervention (8 Weeks)
STARTED	15	15
COMPLETED	12	12
NOT COMPLETED	3	3
Period Title: First Intervention (8 Weeks)
STARTED	12	12
COMPLETED	12	11
NOT COMPLETED	0	1

Baseline Characteristics

Arm/Group Title	HCQ Then Placebo	Placebo Then HCQ	Total
Arm/Group Description	This arm of the study contains half the study population after randomization. The participants in this arm received hydroxychloroquine for 8 weeks and then crossed over to a placebo for 8 weeks. Study staff was blinded to which order they were taking the hydroxychloroquine and placebo in. Hydroxychloroquine: Hydroxychloroquine comes in 200 mg tablets and is taken orally. The dose provided will be based upon a calculation of 6.5 mg/kg (subject's weight), which is the dose range commonly used to treat rheumatoid arthritis and lupus. Dosages will be rounded to the nearest 100 mg.	This arm of the study contains half the study population after randomization. The participants in this arm received hydroxychloroquine for 8 weeks and then crossed over to a placebo for 8 weeks. Study staff was blinded to which order they were taking the hydroxychloroquine and placebo in. Hydroxychloroquine: Hydroxychloroquine comes in 200 mg tablets and is taken orally. The dose provided will be based upon a calculation of 6.5 mg/kg (subject's weight), which is the dose range commonly used to treat rheumatoid arthritis and lupus. Dosages will be rounded to the nearest 100 mg.	Total of all reporting groups
Overall Participants	15	15	30
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	56 (14)	57 (14)	56.5 (11)
Sex: Female, Male (Count of Participants)
Female	13 86.7%	14 93.3%	27 90%
Male	2 13.3%	1 6.7%	3 10%

Outcome Measures

1. Primary Outcome

Title	Insulin Sensitivity Index
Description	We will examine the effect of HCQ on the Matsuda Insulin Sensitivity Index (ISI) during the active treatment phase compared with placebo phase. ISI is based on insulin and glucose levels in a fasting state during an oral glucose tolerance test (OGTT) and is calculated as follows: ISI (Matsuda) = 10000/√ G0 X I0 X Gmean X Imean G0 - fasting plasma glucose (mg/dL) I0 - fasting plasma insulin (mIU/L) Gmean - mean plasma glucose during OGTT (mg/dL) Imean - mean plasma insulin during OGTT (mIU/L)
Time Frame	Baseline and Week 8

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Hydroxychloroquine	Placebo
Arm/Group Description	This group contains results for when study participants were taking hydroxychlorquine. Hydroxychloroquine: Hydroxychloroquine comes in 200 mg tablets and is taken orally. The dose provided was based upon a calculation of 6.5 mg/kg (subject's weight), which is the dose range commonly used to treat rheumatoid arthritis and lupus. Dosages will be rounded to the nearest 100 mg.	This arm group contains the results for patients while they were on placebo.
Measure Participants	23	23
Baseline	7.7 (4.8)	7.7 (4.8)
Period Value	8.1 (4.5)	7.8 (4.0)
Change	0.4 (2.9)	0.14 (3.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Hydroxychloroquine, Placebo
	Comments	The P-value calculated was for the difference betweeen the change during hydroxychloroquine versus placebo using Wilcoxon signed-rank tests.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.930
	Comments	Unadjusted
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Hydroxychloroquine, Placebo
	Comments	The P-value was calculated for the difference between the change during hydroxychloroquine versus placebo from a linear regression model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.785
	Comments	Adjusted for weight change.
	Method	Regression, Linear
	Comments

2. Secondary Outcome

Title	HOMA-IR
Description	We will examine the effect of HCQ on HOMA-IR during the active treatment phase compared with placebo phase. HOMA-IR = (Glucose x insulin)/405
Time Frame	Baseline and Week 8

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Hydroxychloroquine	Placebo
Arm/Group Description	This group contains results for when study participants were taking hydroxychlorquine. Hydroxychloroquine: Hydroxychloroquine comes in 200 mg tablets and is taken orally. The dose provided was based upon a calculation of 6.5 mg/kg (subject's weight), which is the dose range commonly used to treat rheumatoid arthritis and lupus. Dosages will be rounded to the nearest 100 mg.	This arm group contains the results for patients while they were on placebo.
Measure Participants	23	23
Baseline	2.0 (1.7)	2.0 (1.7)
Period	1.7 (1.0)	1.6 (0.79)
Change	-0.3 (1.5)	-0.42 (1.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Hydroxychloroquine, Placebo
	Comments	P-value for the difference between change during hydroxychloroquine versus placebo using Wilcoxon signed-rank tests.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.575
	Comments	Unadjusted P-value
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Hydroxychloroquine, Placebo
	Comments	P-value for the difference between the change during hydroxychloroquine versus placebo from a linear regression model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.308
	Comments	Adjusted for weight change.
	Method	Regression, Linear
	Comments

3. Secondary Outcome

Title	HOMA-B
Description	HOMA-B = (360 x Insulin)/(Glucose - 63)
Time Frame	Baseline and Week 8

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Hydroxychloroquine	Placebo
Arm/Group Description	This group contains results for when study participants were taking hydroxychlorquine. Hydroxychloroquine: Hydroxychloroquine comes in 200 mg tablets and is taken orally. The dose provided was based upon a calculation of 6.5 mg/kg (subject's weight), which is the dose range commonly used to treat rheumatoid arthritis and lupus. Dosages will be rounded to the nearest 100 mg.	This arm group contains the results for patients while they were on placebo.
Measure Participants	23	23
Baseline	116.5 (100.4)	116.5 (100.4)
Period	110.8 (81.6)	109.7 (82.6)
Change	-5.8 (72.9)	-6.8 (78.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Hydroxychloroquine, Placebo
	Comments	P-value for the difference betweeen change during hydroxychloroquine versus placebo suing Wilcoxon signed-rank tests.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.468
	Comments	Unadjusted
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Hydroxychloroquine, Placebo
	Comments	P-value for the difference between the change during hydroxychloroquine versus placebo from a linear regression model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.902
	Comments	Adjusted for weight change.
	Method	Regression, Linear
	Comments

4. Secondary Outcome

Title	Total Cholesterol
Description	mg/dL
Time Frame	Baseline and Week 8

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Hydroxychloroquine	Placebo
Arm/Group Description	This group contains results for when study participants were taking hydroxychlorquine. Hydroxychloroquine: Hydroxychloroquine comes in 200 mg tablets and is taken orally. The dose provided was based upon a calculation of 6.5 mg/kg (subject's weight), which is the dose range commonly used to treat rheumatoid arthritis and lupus. Dosages will be rounded to the nearest 100 mg.	This arm group contains the results for patients while they were on placebo.
Measure Participants	23	23
Baseline	192.4 (37.5)	192.4 (37.5)
Period	179.7 (44.3)	189.4 (37.9)
Change	-12.7 (20.0)	-3.0 (22.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Hydroxychloroquine, Placebo
	Comments	P-value for the difference between the change during hydroxychloroquine versus placebo using Wilcoxon signed-rank tests.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.004
	Comments	Unadjusted
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Hydroxychloroquine, Placebo
	Comments	P-value for the difference between the change during hydroxychloroquine versus placebo from a linear regression model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.004
	Comments	Adjusted for weight change.
	Method	Regression, Linear
	Comments

5. Secondary Outcome

Title	LDL Cholesterol
Description	mg/dL
Time Frame	Baseline and Week 8

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Hydroxychloroquine	Placebo
Arm/Group Description	This group contains results for when study participants were taking hydroxychlorquine. Hydroxychloroquine: Hydroxychloroquine comes in 200 mg tablets and is taken orally. The dose provided was based upon a calculation of 6.5 mg/kg (subject's weight), which is the dose range commonly used to treat rheumatoid arthritis and lupus. Dosages will be rounded to the nearest 100 mg.	This arm group contains the results for patients while they were on placebo.
Measure Participants	23	23
Baseline	114.1 (29.8)	114.1 (29.8)
Period	101.7 (36.7)	109.9 (33.1)
Change	-12.4 (20.1)	-4.2 (17.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Hydroxychloroquine, Placebo
	Comments	P-value for the difference between the change during hydroxychloroquine versus placebo using Wilcoxon signed-rank tests.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.009
	Comments	Unadjusted
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Hydroxychloroquine, Placebo
	Comments	P-value for the difference between the change during hydroxychloroquine versus placebo from a linear regression model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.011
	Comments	Adjusted for weight change.
	Method	Regression, Linear
	Comments

6. Secondary Outcome

Title	HDL Cholesterol
Description	mg/dL
Time Frame	Baseline and Week 8

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Hydroxychloroquine	Placebo
Arm/Group Description	This group contains results for when study participants were taking hydroxychlorquine. Hydroxychloroquine: Hydroxychloroquine comes in 200 mg tablets and is taken orally. The dose provided was based upon a calculation of 6.5 mg/kg (subject's weight), which is the dose range commonly used to treat rheumatoid arthritis and lupus. Dosages will be rounded to the nearest 100 mg.	This arm group contains the results for patients while they were on placebo.
Measure Participants	23	23
Baseline	58.1 (17.9)	58.1 (17.9)
Period	59.4 (18.2)	60.3 (17.8)
Change	1.3 (6.7)	2.2 (9.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Hydroxychloroquine, Placebo
	Comments	P-value for the difference between the change during hydroxychloroquine versus placebo using Wilcoxon signed-rank tests.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.730
	Comments	Unadjusted
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Hydroxychloroquine, Placebo
	Comments	P-value for the difference between the change during hydroxychloroquine versus placebo from a linear regression model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.208
	Comments	Adjusted for weight change.
	Method	Regression, Linear
	Comments

7. Secondary Outcome

Title	Triglycerides
Description	mg/dL
Time Frame	Baseline and Week 8

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Hydroxychloroquine	Placebo
Arm/Group Description	This group contains results for when study participants were taking hydroxychlorquine. Hydroxychloroquine: Hydroxychloroquine comes in 200 mg tablets and is taken orally. The dose provided was based upon a calculation of 6.5 mg/kg (subject's weight), which is the dose range commonly used to treat rheumatoid arthritis and lupus. Dosages will be rounded to the nearest 100 mg.	This arm group contains the results for patients while they were on placebo.
Measure Participants	23	23
Baseline	100.6 (44.0)	100.6 (44.0)
Period	92.4 (41.7)	95.6 (44.9)
Change	-8.2 (45.0)	-5.0 (20.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Hydroxychloroquine, Placebo
	Comments	P-value for the difference between the change during hydroxychloroquine versus placebo using Wilcoxon signed-rank tests.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.487
	Comments	Unadjusted P-value.
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Hydroxychloroquine, Placebo
	Comments	P-value for the difference between the change during hydroxycholorquine versus placebo from a linear regression model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.884
	Comments	P-value adjusted for weight change.
	Method	Regression, Linear
	Comments

Adverse Events

Arm/Group Title	Hydroxychloroquine		Placebo
Arm/Group Description	Participants received hydroxychloroquine (HCQ) for 8 weeks. Hydroxychloroquine: Hydroxychloroquine comes in 200 mg tablets and is taken orally. The dose provided will be based upon a calculation of 6.5 mg/kg (subject's weight), which is the dose range commonly used to treat rheumatoid arthritis and lupus. Dosages will be rounded to the nearest 100 mg.		Participants received Placebo tablets for 8 weeks.
All Cause Mortality
	Hydroxychloroquine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Hydroxychloroquine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/15 (0%)		0/15 (0%)
Other (Not Including Serious) Adverse Events
	Hydroxychloroquine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/15 (13.3%)		0/15 (0%)
Metabolism and nutrition disorders
Liver Function Test Abnormality	1/15 (6.7%)	1	0/15 (0%)	0
Skin and subcutaneous tissue disorders
Rash	1/15 (6.7%)	1	0/15 (0%)	0

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.