Vitamin D Effects on Prostate Pathology

Study Overview
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Brief Summary
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There is much interest in understanding the role that vitamin D3 (cholecalciferol) plays in various cancers, and in the prognosis of various cancers once they are discovered. The purpose of this study is to examine the effects of vitamin D on prostate cancer-associated lesions and on vitamin D metabolites in prostate tissue. We will give vitamin D3 to men when they are scheduled to have their prostate removed because of cancer. The men will take vitamin D at one of 3 doses for 4-6 weeks, until the surgery is performed. We will compare the prostate tissue taken from the men receiving the higher doses of vitamin D to tissue from men assigned to the lower doses. We expect to find that the prostate removed at surgery from men who received the high-dose vitamin D treatment will appear more normal, and less cancer like. In addition, we will measure vitamin D metabolites in the prostate to confirm that these did accumulate in the prostate to bring about the effects observed.

Detailed Description
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Epidemiologic, laboratory, and clinical reports all suggest that vitamin D3 (cholecalciferol) plays a desirable role in the prevention and prognosis of prostate and other cancers. Prostate cancer cells possess both of the enzymes required to convert vitamin D to the active paracrine hormone, calcitriol. However, the dose-response relationship between serum levels of calcidiol (vitamin D status) and prostate tissue levels of calcidiol and calcitriol is yet to be defined. As a neoadjuvant, prior to radical prostatectomy (for 4-6 wk) vitamin D3 [400 IU (control group), 10,000 IU or 40,000 IU/day] will be given to 90 men randomized, double-blinded, 30 per dose. Immediately after surgery, the pathologist will obtain a few grams of prostate tissue, some of which will be used to assay calcidiol and calcitriol within prostate. From the embedded prostate, we will prepare immunohistochemically stained sections to characterize cellular responses and morphological changes. Our hypothesis is that vitamin D will increase intraprostate calcitriol concentration and thereby lower cellular proliferation (as judged by the markers MIB-1 and p27) in zones of Gleason pattern 3 prostate cancer and in pre-cancerous (PIN) lesions. We expect that our results will provide surrogate outcomes to justify larger trials of vitamin D for treatment of prostate cancer. This research has the potential to: 1. Provide direct evidence at the cellular level using clinical samples that vitamin D lowers cellular proliferation in prostate cancer, 2. Provide guidance about the serum calcidiol concentrations (and thereby vitamin D doses) that should be targeted for such studies, and 3. Eventually support other research directed at vitamin D as a primary prevention strategy.

Official Title
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Randomized Trial of the Effects of Vitamin D on Prostate Cancer-associated Lesions and on Vitamin D Metabolites in Prostate

Conditions
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Prostate Cancer

Intervention / Treatment
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* Dietary Supplement: vitamin D3 (cholecalciferol)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of a Gleason score 6 or 7 adenocarcinoma of the prostate biopsy Patient has elected to have a radical prostatectomy Patient is determined fit for surgery Normal renal and hepatic function Normal serum and urine calcium values Normal serum phosphate values Normal serum parathyroid hormone values Signed written informed consent Exclusion Criteria: Prior use of neoadjuvant androgen deprivation therapy Prior use of 5 alpha reductase inhibitors (finasteride or dutasteride) in last 12 months Previous or concomitant anti-cancer therapy (chemotherapy, radiotherapy) Gleason score 8-10 adenocarcinoma as a biopsy diagnosis History of hypercalcemia/hypercalciuria History of renal disease History of sarcoidosis Vitamin D (cholecalciferol) supplement > 1000 IU/day Inability to comply with a study protocol

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 85 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>vitamin D3 (400 IU/d) | Dietary Supplement: vitamin D3 (cholecalciferol)<br>* liquid vitamin D solution (vitamin D3 in ethanol) taken daily at one of three possible doses (400, 10000, or 40000 IU/d) for 4-6 weeks prior to radical prostatectomy<br>|
| Active Comparator: 2<br>vitamin D3 (10,000 IU/d) | Dietary Supplement: vitamin D3 (cholecalciferol)<br>* liquid vitamin D solution (vitamin D3 in ethanol) taken daily at one of three possible doses (400, 10000, or 40000 IU/d) for 4-6 weeks prior to radical prostatectomy<br>|
| Active Comparator: 3<br>vitamin D3 (40,000 IU/d) | Dietary Supplement: vitamin D3 (cholecalciferol)<br>* liquid vitamin D solution (vitamin D3 in ethanol) taken daily at one of three possible doses (400, 10000, or 40000 IU/d) for 4-6 weeks prior to radical prostatectomy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| immunohistochemical markers of prostate pathology |  | end-of-study | 
| intraprostate vitamin D metabolites |  | end-of-study | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| calcium (serum and urine) |  | biweekly | 
| parathyroid hormone (PTH) |  | baseline, final | 
| prostate specific antigen (PSA) |  | baseline, final | 
| creatinine (serum and urine) |  | biweekly | 
| phosphate (serum) |  | biweekly | 
| serum vitamin D metabolites |  | baseline, final | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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vitamin D, prostate cancer, prostatectomy, pathology, immunohistochemistry