High-Dose Vitamin D Supplementation for ADT-Induced Bone Loss in Older Prostate Cancer Patients

Study Overview
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Brief Summary
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This phase III trial tests whether high-dose vitamin D works in treating androgen-deprivation therapy (ADT)-induced bone loss in patients with prostate cancer who are undergoing androgen-deprivation therapy. Vitamins are substances that the body needs to grow and develop normally. Vitamin D helps the body absorb calcium. Calcium is one of the main building blocks of bone. A lack of vitamin D can lead to bone diseases such as osteoporosis or rickets. This trial may help researcher determine if high-dose vitamin D helps keep bones strong, lowers number of falls, and lessens fatigue in men getting androgen-deprivation therapy.

Detailed Description
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PRIMARY OBJECTIVES: I. To evaluate the effect of high-dose vitamin D (HDVD) supplementation in prostate cancer patients on ADT-induced bone mineral density loss in the total hip over 52 weeks as measured by dual-energy x-ray absorptiometry (DXA). II. To evaluate the effect of HDVD supplementation in prostate cancer patients on ADT-induced bone mineral density loss in the femoral neck, distal radius, and lumbar spine (L1-L4) over 52 weeks as measured by DXA. SECONDARY OBJECTIVES: I. To evaluate the effect of HDVD supplementation on falls over 52 weeks as measured by the Falls History questionnaire. II. To evaluate the effect of HDVD supplementation on fractures over 52 weeks as determined by the Clinical Record Information - Follow-up Form. III. To evaluate the effect of HDVD supplementation on quality of life over 52 weeks as measured by the Functional Assessment of Cancer Therapy- Prostate (FACT-P). EXPLORATORY OBJECTIVES: I. To explore the effect of HDVD supplementation on skeletal muscle mass as measured by DXA. II. To explore the effect of HDVD supplementation on bone biomarkers measured by Millipore Luminex/enzyme-linked immunosorbent assay (ELISA) assays from serum. III. To evaluate the effect of HDVD supplementation on pain, fatigue, sleep, and activities of daily living over 52 weeks as measured by patient-reported outcomes. OUTLINE: After undergoing collection of blood and DXA scan, patents are randomized to 1 of 2 arms. ARM I: Patients receive HDVD orally (PO) throughout the study. Patients also undergo collection of blood and DXA scan on study. ARM II: Patients receive placebo PO throughout the study. Patients also undergo collection of blood and DXA scan on study.

Official Title
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High-dose Vitamin D Supplementation for ADT-Induced Bone Loss in Older Prostate Cancer Patients

Conditions
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Stage I Prostate Cancer AJCC v8, Stage II Prostate Cancer AJCC v8, Stage III Prostate Cancer AJCC v8, Stage IVA Prostate Cancer AJCC v8

Intervention / Treatment
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* Procedure: Biospecimen Collection
* Dietary Supplement: D Vitamin
* Procedure: Dual X-ray Absorptiometry
* Drug: Placebo Administration
* Other: Quality-of-Life Assessment
* Other: Questionnaire Administration


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Be diagnosed with Stage I-IV prostate cancer without metastases to bone (lymph node involvement and prior diagnosis of a primary cancer is allowed) Be age 60 years or older Be starting ADT or have received their first ADT treatment in the past 3 months, with at least 6 planned months of treatment remaining (both luteinizing hormone-releasing hormone (LHRH) antagonists and LHRH agonists are permitted) Have a total serum vitamin D between 10 and 27 ng/ml Have an total serum calcium of less than or equal to 10.5 mg/dl Have a normal GFR (glomerular filtration rate) Agree not to take calcium and/or vitamin D supplements for the duration of the intervention other than those provided by the study Be able to provide written informed consent Be able to swallow pills and capsules Be able to speak and read English Exclusion Criteria: Have long term (greater than 3 months) use of any pharmacologic bone-modifying agent including but not limited to oral or IV bisphosphonates, denosumab, or teriparatide prior to enrollment Have a diagnosis of stage IV chronic kidney disease Have a diagnosis of grade II or greater hypercalcemia (serum calcium greater than 10.5 mg/dl) Have a history of hypercalcemia or vitamin D toxicity/sensitivity

Ages Eligible for Study
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Minimum Age: 60 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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I (HDVD)<br>Patients receive HDVD PO throughout the study. Patients also undergo collection of blood and DXA scan on study. | Procedure: Biospecimen Collection<br>* Undergo collection of blood<br>* Other names: Specimen Collection;Dietary Supplement: D Vitamin<br>* Given PO<br>* Other names: Vitamin-D;Procedure: Dual X-ray Absorptiometry<br>* Undergo DXA scan<br>* Other names: DXA SCAN;Other: Quality-of-Life Assessment<br>* Ancillary studies<br>* Other names: Quality of Life Assessment;Other: Questionnaire Administration<br>* Ancillary studies<br>|
| Placebo Comparator: Arm II (placebo, DXA scan, blood collection, questionnaire)<br>Patients receive placebo PO throughout the study. Patients also undergo collection of blood and DXA scan on study. | Procedure: Biospecimen Collection<br>* Undergo collection of blood<br>* Other names: Specimen Collection;Procedure: Dual X-ray Absorptiometry<br>* Undergo DXA scan<br>* Other names: DXA SCAN;Drug: Placebo Administration<br>* Given PO<br>Other: Quality-of-Life Assessment<br>* Ancillary studies<br>* Other names: Quality of Life Assessment;Other: Questionnaire Administration<br>* Ancillary studies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reduction of bone mineral density (BMD) loss as measured at the total hip | Will determine the efficacy of high-dose vitamin D (HDVD) supplementation versus placebo in reducing BMD loss as measured at the total via dual-energy x-ray absorptiometry (DXA) at 52 weeks. Will use analysis of variance (ANCOVA) with Group (vitamin D or placebo) as the main factor, baseline BMD as covariate, and T3 (week 52) BMD as the outcome. Study site will be included as a random effect independent of residual error. An initial linear mixed model (LMM) will be fit using Restricted Maximum Likelihood (REML) estimation. The significance of the variance due to study site will be tested using the Wald Test. | At 52 weeks | 
| Reduction of BMD loss as measured at the lumbar spine | Will determine the efficacy of HDVD supplementation versus placebo in reducing BMD loss as measured at the lumbar spine total via DXA at 52 weeks. Will use ANCOVA with Group (vitamin D or placebo) as the main factor, baseline BMD as covariate, and T3 (week 52) BMD as the outcome. Study site will be included as a random effect independent of residual error. An initial LMM will be fit using REML estimation. The significance of the variance due to study site will be tested using the Wald Test. | At 52 weeks |