High Dose Vitamin D vs Standard Dose Vitamin D Study

• Sponsor: Mothaffar Rimawi (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01988090
• Collaborator: (none)
• Enrollment: 93
• Locations: 2
• Arms: 2
• Actual Duration (Months): 60.3
• Patients Per Site: 46.5
• Patients Per Site Per Month: 0.8

Study Details

Study Description

Brief Summary

This study is being done to look at the difference, if there is a difference between two different doses of Vitamin D and the reduction of joint/muscle pain (arthralgia)that is caused by taking anti-estrogen medications (aromatase inhibitors) by breast cancer patients. The investigators hope to learn if taking a higher dose of Vitamin D is a good way to prevent aromatase inhibitor arthralgia (AIA).

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer	Drug: 800 IU Vitamin D Supplement; Drug: 50,000 IU Vitamin D supplement	Phase 2

Detailed Description

Treatments with anti-estrogen agents for hormone receptor positive breast cancer is the most efficacious of systemic therapies, with aromatase inhibitors (AI's) being considered the most active anti-estrogen therapy in early stage breast cancer. But, use of these treatments has been shown to cause musculoskeletal (joint/muscle) side effects that sometimes cause patients to discontinue the use of them. Also, Vitamin D deficiency is a well know cause of a wide array of musculoskeletal issues. There is evidence that Vitamin D supplementation may help prevent arthralgia while on AI's. Therefore, the investigators want to see if giving a higher dose of Vitamin D could decrease the incidence of AIA as compared to a standard dose of Vitamin D. The investigators believe that this could possibly result in patients continued treatment with AI therapy for hormone receptor positive breast cancer.

Study Design

• Study Type: Interventional
• Actual Enrollment: 93 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomized, Controlled Trial of High Dose vs. Standard Dose Vitamin D for Aromatase-Inhibitor Induced Arthralgia in Breast Cancer Survivors
• Actual Study Start Date: Dec 1, 2013
• Actual Primary Completion Date: Jul 21, 2018
• Actual Study Completion Date: Dec 10, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: High Dose Vitamin D ARM 50,000 IU Vitamin D supplement	Drug: 50,000 IU Vitamin D supplement; High Dose
Active Comparator: 800 IU Vitamin D Supplement 800 IU Vitamin D Supplement	Drug: 800 IU Vitamin D Supplement; Standard Dose

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Aromatase Inhibitor Induced Arthralgia (AIA) After 12 Weeks of Therapy [12 weeks]

   Aromatase Inhibitor Arthralgia (AIA) was assessed by a questionnaire that describe the level of pain experienced by the participant. The questionnaire asks 20 questions scored 0-3 in 8 categories of functioning: dressing, rising, eating, walking, hygiene, reach, grip, and usual activities. An average composite score on the HAQ-II was calculated. The visual analog scale is the other major component of the HAQ-II, which we ask patients to mark where their pain lies on a horizontal line and we converts the number into a score from 0 to 3. For the purposes of this study, AIA will be defined as any of the following criteria: 1) increase in HAQ-II score from baseline by 0.2 or greater; or 2) increase in visual analog pain score by 0.3 or greater.

Secondary Outcome Measures

1. Compliance With Anti-Cancer Treatment [52 Weeks]

   We checked compliance of aromatase inhibitor therapy during the study by reviewing the patient's use of AI drug. This will be done by counting remaining pills in patient's bottles of AI at 52 weeks. A percentage of the number of pills were actually taken of the number of pills should be taken was calculated.

2. Association Between Vitamin D Levels Changes and Treatment. [12 weeks]

   Patients' serum 25-hydroxyvitamin D level were tested at baseline and week 12. The changes between baseline and week 12 were calculated.

Other Outcome Measures

1. Grip Strength [52 weeks]

   Exploratory Endpoints For each patient on the study, grip strength will be correlated with AIA score using Spearman correlation at three time points throughout the study - baseline, week 12, and week 52.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• All participants must be female and at least 21 years of age

• Signed informed consent

• Patients must have had histologically confirmed stage I-III breast carcinoma that is positive for Estrogen Receptor (ER) and/or Progesterone Receptor (PR).

• Post-menopausal

• Beginning adjuvant aromatase inhibitor therapy, with no previous use within the last 6 weeks

• Bisphosphonates are allowed at the treating investigator¡¦s discretion

• Performance status (WHO/ECOG scale) 0-2.

Exclusion Criteria:

• History of kidney stones

• Hypercalcemia at baseline, defined as any corrected calcium greater than the laboratory's normal parameters

• History of either symptomatic hypercalcemia or hyperparathyroidism, at the treating investigator's discretion

• Baseline Vitamin D level greater than 50 ng/mL

• Inability or unwillingness to comply with, or follow study procedures.

• Currently taking Phenytoin or phenobarbital -7 Currently taking cholestyramine or orlistat

• Malabsorption syndrome, such as Crohn's disease

Prohibited Therapies: Patients may not take additional Calcium and Vitamin D aside from the study medications. Patients who are on cholestyramine or orlistat will not be allowed on the trial. Also, patients who are taking phenytoin or phenobarbital are not allowed on the trial either because of interaction between Vitamin D and anti-epileptic medications.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Washington University / Siteman Cancer Center	Saint Louis	Missouri	United States	63110
2	Baylor College of Medicine	Houston	Texas	United States	77030

Sponsors and Collaborators

• Mothaffar Rimawi

Investigators

• Principal Investigator: Mothaffar Rimawi, MD, Baylor College of Medicine

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jul 14, 2015

More Information

Publications

None provided.

• Responsible Party: Mothaffar Rimawi, Professor, Baylor Breast Care Center
• ClinicalTrials.gov Identifier: NCT01988090
• Other Study ID Numbers: H-33261
• First Posted: Nov 20, 2013
• Last Update Posted: Aug 9, 2021
• Last Verified: Aug 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Mothaffar Rimawi, Professor, Baylor Breast Care Center: Breast Cancer; Hormone Receptor Positive; Vitamin D
• Additional relevant MeSH terms: Breast Neoplasms; Vitamin D; Ergocalciferols; Cholecalciferol; Vitamins

Study Results

Participant Flow

Arm/Group Title	High Dose Vitamin D ARM	800 IU Vitamin D Supplement
Arm/Group Description	50,000 IU Vitamin D supplement 50,000 IU Vitamin D supplement: High Dose	800 IU Vitamin D Supplement 800 IU Vitamin D Supplement: Standard Dose
Period Title: Start Treament After Randomization
STARTED	46	47
COMPLETED	44	43
NOT COMPLETED	2	4
Period Title: Start Treament After Randomization
STARTED	44	43
COMPLETED	41	42
NOT COMPLETED	3	1

Baseline Characteristics

Arm/Group Title	High Dose Vitamin D ARM	800 IU Vitamin D Supplement	Total
Arm/Group Description	50,000 IU Vitamin D supplement 50,000 IU Vitamin D supplement: High Dose	800 IU Vitamin D Supplement 800 IU Vitamin D Supplement: Standard Dose	Total of all reporting groups
Overall Participants	46	47	93
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	62.9 (7)	63.8 (8.6)	63.4 (7.8)
Sex: Female, Male (Count of Participants)
Female	46 100%	47 100%	93 100%
Male	0 0%	0 0%	0 0%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	19 41.3%	22 46.8%	41 44.1%
Not Hispanic or Latino	26 56.5%	24 51.1%	50 53.8%
Unknown or Not Reported	1 2.2%	1 2.1%	2 2.2%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	11 23.9%	6 12.8%	17 18.3%
White	33 71.7%	39 83%	72 77.4%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	2 4.3%	2 4.3%	4 4.3%
Region of Enrollment (participants) [Number]
United States	46 100%	47 100%	93 100%
Serum 25-hydroxyvitamin D level (ng/mL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [ng/mL]	21.7 (8.7)	24.2 (7.1)	23 (8)

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Aromatase Inhibitor Induced Arthralgia (AIA) After 12 Weeks of Therapy
Description	Aromatase Inhibitor Arthralgia (AIA) was assessed by a questionnaire that describe the level of pain experienced by the participant. The questionnaire asks 20 questions scored 0-3 in 8 categories of functioning: dressing, rising, eating, walking, hygiene, reach, grip, and usual activities. An average composite score on the HAQ-II was calculated. The visual analog scale is the other major component of the HAQ-II, which we ask patients to mark where their pain lies on a horizontal line and we converts the number into a score from 0 to 3. For the purposes of this study, AIA will be defined as any of the following criteria: 1) increase in HAQ-II score from baseline by 0.2 or greater; or 2) increase in visual analog pain score by 0.3 or greater.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

ITT population. All patients who were randomized in the study were included in the overall evaluation of response (intent-to-treat analysis).

Arm/Group Title	High Dose Vitamin D ARM	800 IU Vitamin D Supplement
Arm/Group Description	50,000 IU Vitamin D supplement 50,000 IU Vitamin D supplement: High Dose	800 IU Vitamin D Supplement 800 IU Vitamin D Supplement: Standard Dose
Measure Participants	46	47
development of AIA	25 54.3%	27 57.4%
no development of AIA	21 45.7%	20 42.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	High Dose Vitamin D ARM, 800 IU Vitamin D Supplement
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.7635
	Comments
	Method	Chi-squared
	Comments

2. Secondary Outcome

Title	Compliance With Anti-Cancer Treatment
Description	We checked compliance of aromatase inhibitor therapy during the study by reviewing the patient's use of AI drug. This will be done by counting remaining pills in patient's bottles of AI at 52 weeks. A percentage of the number of pills were actually taken of the number of pills should be taken was calculated.
Time Frame	52 Weeks

Outcome Measure Data

Analysis Population Description

Compliance was assessed at week 52. Only 14 patients have compete the data collection. Form was not completed due to not starting the treatment, or not finishing the treatment, or no source data.

Arm/Group Title	High Dose Vitamin D ARM	800 IU Vitamin D Supplement
Arm/Group Description	50,000 IU Vitamin D supplement 50,000 IU Vitamin D supplement: High Dose	800 IU Vitamin D Supplement 800 IU Vitamin D Supplement: Standard Dose
Measure Participants	6	8
Mean (Standard Deviation) [percentage of pills taken]	0.981 (0.047)	0.965 (0.07)

3. Secondary Outcome

Title	Association Between Vitamin D Levels Changes and Treatment.
Description	Patients' serum 25-hydroxyvitamin D level were tested at baseline and week 12. The changes between baseline and week 12 were calculated.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

Patients who had serum 25-hydroxyvitamin D level tested at baseline and week 12 were included in the analysis.

Arm/Group Title	High Dose Vitamin D ARM	800 IU Vitamin D Supplement
Arm/Group Description	50,000 IU Vitamin D supplement 50,000 IU Vitamin D supplement: High Dose	800 IU Vitamin D Supplement 800 IU Vitamin D Supplement: Standard Dose
Measure Participants	39	36
Mean (Standard Deviation) [ng/mL]	28.8 (14.5)	5.2 (7.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	High Dose Vitamin D ARM, 800 IU Vitamin D Supplement
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

4. Other Pre-specified Outcome

Title	Grip Strength
Description	Exploratory Endpoints For each patient on the study, grip strength will be correlated with AIA score using Spearman correlation at three time points throughout the study - baseline, week 12, and week 52.
Time Frame	52 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	56 weeks. Adverse events experienced by participants were collected and reported from initiation of study medication, throughout the study (52 weeks treatment), and within 30 days of the last dose of study medication.
Arm/Group Title	High Dose Vitamin D ARM		800 IU Vitamin D Supplement
Arm/Group Description	50,000 IU Vitamin D supplement 50,000 IU Vitamin D supplement: High Dose		800 IU Vitamin D Supplement 800 IU Vitamin D Supplement: Standard Dose
All Cause Mortality
	High Dose Vitamin D ARM		800 IU Vitamin D Supplement
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/44 (0%)		0/43 (0%)
Serious Adverse Events
	High Dose Vitamin D ARM		800 IU Vitamin D Supplement
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/44 (4.5%)		0/43 (0%)
Infections and infestations
Skin infection	1/44 (2.3%)	1	0/43 (0%)	0
Renal and urinary disorders
Renal and urinary disorders - Other, specify	1/44 (2.3%)	1	0/43 (0%)	0
Other (Not Including Serious) Adverse Events
	High Dose Vitamin D ARM		800 IU Vitamin D Supplement
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	35/44 (79.5%)		36/43 (83.7%)
Endocrine disorders
Hypothyroidism	2/44 (4.5%)	2	0/43 (0%)	0
Gastrointestinal disorders
Constipation	3/44 (6.8%)	3	1/43 (2.3%)	1
Diarrhea	2/44 (4.5%)	2	0/43 (0%)	0
Gastroesophageal reflux disease	1/44 (2.3%)	1	2/43 (4.7%)	2
General disorders
Fatigue	6/44 (13.6%)	6	4/43 (9.3%)	4
Pain	2/44 (4.5%)	2	1/43 (2.3%)	1
Musculoskeletal and connective tissue disorders
Arthralgia	20/44 (45.5%)	25	19/43 (44.2%)	22
Arthritis	2/44 (4.5%)	2	1/43 (2.3%)	1
Myalgia	0/44 (0%)	0	3/43 (7%)	3
Neck pain	2/44 (4.5%)	2	0/43 (0%)	0
Pain in extremity	2/44 (4.5%)	2	7/43 (16.3%)	7
Nervous system disorders
headache	2/44 (4.5%)	2	1/43 (2.3%)	1
Peripheral sensory neuropathy	9/44 (20.5%)	12	1/43 (2.3%)	1
Psychiatric disorders
Anxiety	0/44 (0%)	0	3/43 (7%)	3
Depression	4/44 (9.1%)	4	3/43 (7%)	3
Insomnia	1/44 (2.3%)	1	3/43 (7%)	3
Reproductive system and breast disorders
vaginal dryness	5/44 (11.4%)	5	3/43 (7%)	4
Respiratory, thoracic and mediastinal disorders
Cough	2/44 (4.5%)	2	0/43 (0%)	0
Vascular disorders
Hot flashes	23/44 (52.3%)	25	20/43 (46.5%)	22
Hypertension	4/44 (9.1%)	4	1/43 (2.3%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE 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.