High-dose Vitamin D Supplementation for ADT-induced Side Effects

Study Overview
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Brief Summary
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The purpose of this study is to test the efficacy of a high-dose vitamin D supplementation regimen in reducing androgen deprivation therapy (ADT)-related side effects in older prostate cancer patients on ADT. The proposed study is a randomized, double-blind, 2-arm, controlled clinical trial that will accrue 76 prostate cancer patients without severe bone loss, aged 60 and older, beginning ADT, and scheduled to receive at least 6 months more of ADT. Participants will be randomized to: 1) weekly high-dose vitamin D3 (50,000 IU) or 2) vitamin D placebo only for a period of 24 weeks. Both groups will also receive a daily multivitamin and calcium supplement.

Detailed Description
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The investigators hypothesize high-dose vitamin D supplementation will reduce androgen deprivation therapy (ADT)-related side effects including ADT-induced bone loss, decreased muscle mass, falls, reduced muscle strength, and diminished physical performance in older prostate cancer patients. The vitamin D supplementation is aimed at reducing fracture risk by maintaining proper bone density, thereby preventing osteoporotic/osteopenic conditions and increasing muscle mass. Both vitamin D and exercise are efficacious in maintaining proper bone health and muscle mass among the general population, but little research has been done on prostate cancer patients and survivors. Vitamin D could reduce fracture risk among prostate cancer survivors.

Official Title
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High-dose Vitamin D Supplementation for ADT-induced Side Effects

Conditions
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Prostatic Neoplasms, Bone Mineral Density Quantitative Trait Locus 3

Intervention / Treatment
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* Dietary Supplement: vitamin D
* Dietary Supplement: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have a confirmed diagnosis of stage I-IIIA prostate cancer Within 6 months of starting ADT with an additional 6 more months planned. Participants must have sub-optimal vitamin D levels of <32 ng/ml. Participants must agree not to take calcium and/or vitamin D supplements for the duration of the intervention other than those provided. Participants must have an ionized serum calcium level within normal limits (1.19-1.29mmol/L) and a total corrected serum calcium of ≤10.5 mg/dl. No contraindications for fitness testing and no physical limitations (e.g. cardiorespiratory, orthopedic, nervous system) as assessed by their physician. Able to read English (since the assessment materials are in printed format). Able to swallow medication and provide written informed consent. 60 years of age or older. Exclusion Criteria: Previously verified diagnosis of osteoporosis (any t-score ≤ -2.5). Patients on antiresorptive drugs (i.e. bisphosphonates) within the past year. Patients with hypercalcemia (corrected serum Ca > 10.5 mg/dl) or a history of hypercalcemia or vitamin D toxicity/sensitivity. Patients with impaired renal function (CrCl < 60 mL/min) or who had kidney stones (calcium salt) within the past 5 years. Myocardial infarction within the past year.

Ages Eligible for Study
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Minimum Age: 60 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Vitamin D3<br>Vitamin D3 50,000 IU: Patients will be assigned to receive weekly high-dose vitamin D (50,000 IU/week) along with a daily multivitamin (600 IU/day vitamin D + 210 mg/day calcium) and calcium supplements (1,000 mg/day calcium) for a period of 24 weeks. | Dietary Supplement: vitamin D<br>* 50,000IU/week of vitamin D3<br>|
| Placebo Comparator: Control<br>Control: Patients will be assigned to receive a weekly vitamin D placebo along with a daily multivitamin (600 IU/day vitamin D + 210 mg/day calcium)and calcium supplements (1,000 mg/day calcium) for a period of 24 weeks. | Dietary Supplement: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| bone mineral density | mean difference in bone mineral density between treatment group and control group | after 24 weeks | 
| bone biomarkers | amino-terminal collagen crosslinks (NTx) and bone-specific alkaline phosphatase (BSAP) | after 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| muscle mass | muscle mass as assessed by dual energy x-ray absorptiometry | after 24 weeks | 
| muscular strength | as assessed by Handgrip Dynamometer and 7-10 Repetition Maximum | after 24 weeks | 
| physical performance | as assessed by falls, physical performance battery, and 6-min walk test | after 24 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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prostate cancer, bone density, vitamin D, micronutrients, pharmacologic actions