Vitamin D3 Supplementation for Low-Risk Prostate Cancer: A Randomized Trial (VD3PCa)

March 14, 2024 updated by: VA Office of Research and Development
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 1,25 dihydroxyvitamin D3 (VD3) 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).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

130

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • South Carolina
      • Charleston, South Carolina, United States, 29425
        • Medical University of South Carolina
      • Charleston, South Carolina, United States, 29401-5799
        • Ralph H. Johnson VA Medical Center, Charleston, SC

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

19 years to 90 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Male 19 - 90 years old - Low-grade prostate cancer
  • Clinical Stage T1C or T2a
  • Serum PSA < 10.0 ng/ml
  • Gleason Score < or = to 6 (either architectural pattern < or = to 3)
  • Decision to monitor prostate cancer in Active Surveillance
  • Serum creatinine < 2.0 mg/dL
  • Serum phosphorus > 2.3 and < 4.8 mg/dL
  • Serum calcium > 8.5 and < 10.5 mg/dL
  • Must be capable of giving consent to participate in the study

Exclusion Criteria:

  • Any concurrent malignancy, except non-melanoma skin cancer
  • History of sarcoidosis
  • History of Primary Hyperparathyroidism
  • History of hypercalcemia
  • Vitamin D supplementation > 2,000 IU daily
  • Lithium medication

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Arm 1
4,000 IU of VD3 for one year
Drug: Vitamin D3
4,000 IU of VD3 for at least one year
Placebo Comparator: Arm 2
placebo for one year
Drug: Placebo
Placebo for at least one year

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Pathology Status
Time Frame: one year
pathology status will be measured by the number of positive cores in prostate needle biopsy specimens between baseline and the repeat standard of care prostate biopsy at the end of the study.
one year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Veteran Subjects Who Will Undergo Additional Treatment
Time Frame: 2 years
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 (prostatectomy or radiation therapy), following the outcome of repeat biopsy.
2 years
PSA and Serum Vitamin D
Time Frame: One year
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.
One year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

VA Office of Research and Development

Collaborators

Medical University of South Carolina

Investigators

  • Principal Investigator: Sebastiano Gattoni-Celli, MD, Ralph H. Johnson VA Medical Center, Charleston, SC

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 3, 2013

Primary Completion (Actual)

October 18, 2018

Study Completion (Actual)

May 11, 2020

Study Registration Dates

First Submitted

December 27, 2012

First Submitted That Met QC Criteria

December 27, 2012

First Posted (Estimated)

January 3, 2013

Study Record Updates

Last Update Posted (Actual)

March 18, 2024

Last Update Submitted That Met QC Criteria

March 14, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CLIN-007-12S
  • Pro00019745 (Other Identifier: Medical University of South Carolina IRB)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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