Vitamin D Supplementation in Veterans With Early-Stage Prostate Cancer (vit D & PCa)

Vitamin D promotes the differentiation of prostate cancer cells, maintains the differentiated phenotype of prostate epithelial cells, and can induce prostate cancer cell death, raising the possibility that vitamin D deficiency over time promotes the progression of subclinical prostate cancer to clinical disease. The investigators propose to conduct a clinical study aimed at measuring the efficacy of vitamin D3 (4000IU/day) supplementation in Veterans diagnosed with low-risk, early-stage prostate cancer, who elect to have their disease monitored through active surveillance. The successful completion of this proposed clinical study will allow us to determine whether correcting vitamin D deficiency in Veterans diagnosed with early-stage prostate cancer will prevent progression of their disease and improve their prognosis.

Study Overview

• Status: Completed
• Conditions: Prostate Cancer
• Intervention / Treatment: Drug: vitamin D3; Drug: Placebo daily for one year

Detailed Description

Vitamin D promotes the differentiation of prostate cancer (PCa) cells, maintains the differentiated phenotype of prostate epithelial cells, and can induce prostate cancer cell death, raising the possibility that vitamin D deficiency over time promotes the progression of subclinical PCa to clinical disease. These considerations support the use of vitamin D3 as a chemopreventive agent.

We hypothesize that a daily dose of vitamin D3 (4,000 IU) taken for one year by Veterans diagnosed with low-risk, early-stage PCa, who are eligible for active surveillance will: a) result in a measurable decrease of serum PSA levels in a significant number of enrolled subjects, and b) be associated with a stabilization or improvement of their PCa pathology, as assessed through histological examination of prostate tissue biopsy specimens (Gleason score and percent of positive biopsies) obtained at the end of the study, as part of their standard medical care for active surveillance.

This VA Merit application proposes to conduct a randomized, placebo-controlled clinical study aimed at measuring the efficacy of vitamin D3 (4000IU/day) supplementation in Veterans diagnosed with early-stage prostate cancer, who elect to have their disease monitored through active surveillance (before considering definitive therapy). The main objectives of this proposed clinical study are as follows:

1. To determine whether a daily supplement of 4,000 IU of vitamin D3 taken for twelve months will result in a measurable and significant decrease of serum PSA levels in Veterans diagnosed with low-risk, early stage PCa (Gleason score 6, PSA 10, clinical stage T1C or T2a), who elect to have their disease monitored through active surveillance for at least one year.
2. To determine in enrolled Veterans the pathology status of their PCa by analyzing prostate tissue biopsy specimens at the end of the study (Gleason score and percentage of positive biopsies), and by comparing them with those obtained before enrollment in this study, as part of their standard medical care.

The implementation of these proposed studies will allow us to assess whether vitamin D3 supplementation can be utilized as a chemopreventive regimen in Veterans diagnosed with low-risk, early stage PCa, and provide a useful addition to active surveillance.

• Study Type: Interventional
• Enrollment (Actual): 83
• Phase: Phase 2

Contacts and Locations

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

Eligibility Criteria

• Ages Eligible for Study: 19 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Male Veterans (> 18 years of age) recently diagnosed with low-risk PCa (histologically documented adenocarcinoma of the prostate)
• A serum PSA value of up to 10.0 ng/ml, and a Gleason score of six or less (three or less in either architectural pattern)

• For the purpose of eligibility, these additional criteria will be verified: *serum creatinine 2.0 mg/dL

  • serum phosphate (measured as phosphorus) > 2.3 and < 4.8 mg/dL
  • serum calcium > 8.5 and < 10.5 mg/dL

Exclusion Criteria:

• Subjects with any concurrent malignancy, except non-melanoma skin cancer
• Subjects with a history of sarcoidosis
• Subjects with a history of high-dose (1,000 IU per day) vitamin D supplementation
• Subjects with a history of hypercalcemia
• Subjects who use lithium as a medication

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Vitamin D3; 4,000 IU vitamin D3 daily for one year	Drug: vitamin D3; 4,000 IU daily for one year
Placebo Comparator: Placebo; Placebo daily for one year	Drug: Placebo daily for one year; Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PSA Slope (Trajectory) or the Change in PSA Level Over Time	Change in PSA (ng/mL) from baseline to 1 year visit, which include the baseline through 1 year follow-up.	1 year (visits # 1-8)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Positive Biopsy Cores (Out of Twelve) Compared to the Corresponding Values Assessed Before Enrollment	Change in the number of positive cores per subject from the pre-study prostate biopsy to the repeat prostate biopsy following study participation.	1 year

Collaborators and Investigators

• 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

Study Major Dates

• Study Start (Actual): January 7, 2010
• Primary Completion (Actual): December 15, 2013
• Study Completion (Actual): October 30, 2014

Study Registration Dates

• First Submitted: August 4, 2009
• First Submitted That Met QC Criteria: August 5, 2009
• First Posted (Estimate): August 6, 2009

Study Record Updates

• Last Update Posted (Actual): October 9, 2017
• Last Update Submitted That Met QC Criteria: September 8, 2017
• Last Verified: September 1, 2017

More Information

Terms related to this study

• Keywords: prostate cancer; vitamin D
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms; Physiological Effects of Drugs; Micronutrients; Vitamins; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Vitamin D; Cholecalciferol
• Other Study ID Numbers: CLIN-004-09S; MUSC IRB HR#19344 (Other Identifier: MUSC 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