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

NCT ID: NCT01759771

Last Updated: 2024-03-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 130 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-01-03
• Study Completion Date: 2020-05-11

Brief 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 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).

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.

Conditions

Prostate Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Arm 1

4,000 IU of VD3 for one year

Group Type: EXPERIMENTAL

Vitamin D3

Intervention Type: DRUG

4,000 IU of VD3 for at least one year

Arm 2

placebo for one year

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo for at least one year

Interventions

Vitamin D3

4,000 IU of VD3 for at least one year

Intervention Type: DRUG

Placebo

Placebo for at least one year

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 19 Years
• Maximum Eligible Age: 90 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Medical University of South Carolina

OTHER

Sponsor Role: collaborator

VA Office of Research and Development

FED

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Sebastiano Gattoni-Celli, MD

Role: PRINCIPAL_INVESTIGATOR

Ralph H. Johnson VA Medical Center, Charleston, SC

Locations

Ralph H. Johnson VA Medical Center, Charleston, SC

Charleston, South Carolina, United States

Medical University of South Carolina

Charleston, South Carolina, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

Pro00019745

Identifier Type: OTHER

Identifier Source: secondary_id

CLIN-007-12S

Identifier Type: -

Identifier Source: org_study_id