Vitamin D3 Supplementation for Low-Risk Prostate Cancer: A Randomized Trial (VD3 PC)

This study is currently recruiting participants.
Verified November 2013 by Department of Veterans Affairs
Sponsor:
Information provided by (Responsible Party):
Department of Veterans Affairs
ClinicalTrials.gov Identifier:
NCT01759771
First received: December 27, 2012
Last updated: November 20, 2013
Last verified: November 2013
  Purpose

Vitamin D promotes the differentiation of prostate cancer cells and maintains the differentiated phenotype of prostate epithelial cells. The results of our 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. We 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).


Condition Intervention Phase
Prostate Cancer
Drug: Vitamin D3
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: Vitamin D3 Supplementation for Low-Risk Prostate Cancer: A Randomized Trial

Resource links provided by NLM:


Further study details as provided by Department of Veterans Affairs:

Primary Outcome Measures:
  • Pathology Status [ Time Frame: one year ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Number of Veteran subjects who will undergo additional treatment [ Time Frame: more than one year ] [ Designated as safety issue: No ]
    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.

  • PSA and serum Vitamin D [ Time Frame: One year ] [ Designated as safety issue: No ]
    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).


Estimated Enrollment: 136
Study Start Date: January 2013
Estimated Study Completion Date: December 2017
Estimated Primary Completion Date: December 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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, we 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, we 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.

  Eligibility

Ages Eligible for Study:   19 Years to 90 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 < 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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01759771

Contacts
Contact: Sebastiano Gattoni-Celli, MD (843) 876-5103 Sebastiano.Gattoni-Celli@va.gov
Contact: Linda H Ambrose, RN BSN BS (843) 792-8303 ambrosel@musc.edu

Locations
United States, South Carolina
Ralph H Johnson VA Medical Center, Charleston Recruiting
Charleston, South Carolina, United States, 29401-5799
Contact: M. Rita I Young, PhD    843-789-6707    rita.young@va.gov   
Contact: Benjamin R O'Dell, MPH BS    (843) 789-6710    benjamin.o'dell@va.gov   
Principal Investigator: Sebastiano Gattoni-Celli, MD         
Sponsors and Collaborators
Investigators
Principal Investigator: Sebastiano Gattoni-Celli, MD Ralph H Johnson VA Medical Center, Charleston
  More Information

No publications provided

Responsible Party: Department of Veterans Affairs
ClinicalTrials.gov Identifier: NCT01759771     History of Changes
Other Study ID Numbers: CLIN-007-12S, Pro00019745
Study First Received: December 27, 2012
Last Updated: November 20, 2013
Health Authority: United States: Federal Government
United States: Food and Drug Administration

Keywords provided by Department of Veterans Affairs:
Prostate Cancer
Vitamin D3
Active surveillance

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases
Cholecalciferol
Vitamin D
Ergocalciferols
Vitamins
Micronutrients
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Bone Density Conservation Agents

ClinicalTrials.gov processed this record on April 17, 2014