Vitamin D3 Supplementation for Low-Risk Prostate Cancer: A Randomized Trial
Condition: Prostate Cancer
MeSH terms: Prostatic Neoplasms
Study type: Interventional
Phase: Phase 2

Summary: 
      Vitamin D promotes the differentiation of prostate cancer cells and maintains the
      differentiated phenotype of prostate epithelial cells. The results of the investigators'
      clinical studies indicate that vitamin D3 supplementation results in a decrease of positive
      cancer cores at repeat biopsy in subjects with low-risk prostate cancer. The investigators
      hypothesize that Veterans who have early-stage prostate cancer and who take vitamin D3 at
      4000 international units per day (intervention group) will show an improvement in the number
      of positive cores and in Gleason score at repeat biopsy, and a decreased likelihood of
      undergoing definitive treatment (prostatectomy or radiation therapy), compared to Veteran
      subjects taking placebo (control group).
    

Detailed description: 
      The central hypothesis of this grant application is that vitamin D3 (cholecalciferol)
      supplementation will benefit Veteran subjects diagnosed with early-stage, low-risk prostate
      cancer, who elect to have their disease monitored through active surveillance. Specifically,
      the investigators hypothesize that Veterans who take vitamin D3 at a daily dose of 4000
      international units (IU) for a minimum of one year (intervention group) will show an
      improvement in the number of positive cores and in Gleason score at repeat biopsy, and a
      decreased likelihood of undergoing additional treatment (hormone therapy, prostatectomy or
      radiation therapy), compared to Veterans taking placebo (control group).

      To test this hypothesis, the investigators propose the following Specific Aims:

        1. To determine whether vitamin D3 (4,000 IU per day FOR AT LEAST ONE YEAR) will result in
           a significant improvement of the pathology status at repeat biopsy in Veteran subjects
           taking vitamin D3, compared to Veteran subjects taking placebo. This hypothesis will be
           tested through a randomized clinical trial, which will enroll 136 Veteran subjects (68
           participants per arm), diagnosed with early-stage prostate cancer (Gleason score 6, PSA
           10, clinical stage T1C or T2a). The pathology status will be measured by the change in
           Gleason score and the number of positive cores in prostate needle biopsy specimens
           between baseline and the end of the study. Pre- and post-study biopsies will be
           performed as part of the standard medical care for diagnosis and active surveillance.

        2. To determine whether vitamin D3 supplementation, compared to placebo, will result in a
           significant decrease in the number of Veteran subjects who will undergo additional
           treatment (hormone therapy, prostatectomy or radiation therapy), following the outcome
           of repeat biopsy.

        3. To analyze changes in the serum levels of cholecalciferol, 25(OH)D, 1,25(OH)2D, and
           prostate-specific antigen (PSA) at baseline and at the end of the study, and to estimate
           the associations between changes in these measures and pathology outcomes (Gleason score
           and number of positive cores).

        4. To compare the expression of molecular biomarkers, which are prognostically relevant to
           prostate cancer progression, in pre- and post- treatment biopsy tissue specimens.
           Paraffin-embedded sections will be processed to assess by immunohistochemical techniques
           the expression of the following biomarkers: Vitamin D Receptor (VDR), P21, Tumor Growth
           Factor (TGF ), Cyclooxygenase 2 (COX-2), and NF B. All of these protein products impact
           growth control and chronic inflammation in prostate cancer progression and are
           specifically affected by Vitamin D status.

      Implementation of the proposed studies would demonstrate that Vitamin D3 supplementation
      provides a welcome addition to active surveillance, since patients who respond to Vitamin D3
      supplementation (as indicated by a decrease in score or number of positive cores at repeat
      biopsy) can safely continue active surveillance and would not need definitive treatment. In
      turn, this would result in a decreased likelihood of overtreatment. On the other hand,
      subjects who progress after Vitamin D3 supplementation, as indicated by an increase in
      Gleason score or number of positive cores at repeat biopsy, may have more aggressive disease
      and may need to consider definitive treatment. Therefore, both groups of patients (responders
      as well as non-responders) would benefit from Vitamin D3 supplementation, an intervention
      strategy that is extremely cost-effective and easy to implement.
    

Intervention name(s): Vitamin D3; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): 4,000 IU of VD3 for at least one year; Placebo for at least one year
Intervention MeSH terms: Vitamin D; Cholecalciferol
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment
Keywords: Prostate Cancer; Vitamin D3; Active surveillance