Vitamin D Supplementation in RNA-seq Profiles of Single-core Prostate Samples, Among Veterans (VitD/RNA-seq)

• ClinicalTrials.gov Identifier: NCT04621500
• Recruitment Status: Completed
• First Posted: November 9, 2020
• Last Update Posted: February 8, 2023
• Sponsor: Medical University of South Carolina
• Collaborators: Ralph H. Johnson VA Medical Center; National Institute on Minority Health and Health Disparities (NIMHD)
• Information provided by (Responsible Party): Stephen Savage, Medical University of South Carolina

Study Description

Brief Summary:

Veterans between the ages of 50-75, who are having a prostate biopsy, will be recruited for their permission to collect an extra biopsy core for RNA-sequencing. If the participants' treatment decision is Active Surveillance, they wil be enrolled into the intervention phase of the study. They will receive supplementation with vitamin D3 (4,000 IU) daily with repeat (surveillance) prostate biopsy one year later. At that time an extra prostate sample core will be collected for RNA-sequencing to determine changes over time. Measurements for allostatic load (body stress) will also be collected at the time of enrollment and at the repeat prostate biopsy visit.

Condition or disease	Intervention/treatment	Phase
Prostate Cancer; Vitamin D Deficiency; Stress Reaction	Drug: cholecalciferol	Phase 2

Detailed Description:

This is an open-label pilot study. The goal is to investigate the transcription and biological pathways in prostate cancer that are especially relevant to prostate cancer disparities between African American and Caucasian men. Also, to determine any significant differences in the molecular signature that exist in African American and Caucasian men in relation to their vitamin D levels.

Recruitment will be at the Urology Clinic at the Ralph H. Johnson VA Medical Center in Charleston, SC. Men who are scheduled for a Standard of Care prostate biopsy will be consented for their permission to collect an extra prostate tissue core for RNA-sequencing.

After the pathology report is discussed by their Urologist, and the treatment decision is Active Surveillance, the participant is enrolled into the Intervention Phase. At that time, baseline allostatic load measurements (Blood pressure, pulse, waist/hip ratio, height and weight for BMI) and bloodwork: (lipid panel, HgbA1c, albumin and creatinine, IL-6, CRP, and DHEA-s) plus a vitamin D level, will be collected. Vitamin D3 softgels (4,000 IU) daily (six months supply) will be dispensed. A Social Determinants survey will also be dispensed for subject completion.

At the Urology Standard of Care six month follow-up appointment, the a vitamin D serum level will be collected and the next six months supply of vitamin D3 will be dispensed.

At the Urology Standard of Care follow-up (repeat at 1 year) surveillance prostate biopsy, an extra prostate tissue core will be collected for RNA-sequencing. The allostatic load measurements and bloodwork will also be obtained. A single blood vial will also be collected for ancestry markers.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 36 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: Single, open-label group
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: Vitamin D Supplementation in RNA-seq Profiles of Single-core Prostate Samples, Including Diversity and Stress Determinants, Among Veterans
• Actual Study Start Date: June 4, 2019
• Actual Primary Completion Date: February 4, 2022
• Actual Study Completion Date: February 4, 2022

Arms and Interventions

Arm	Intervention/treatment
Open label; All enrolled subjects will receive vitamin D3 at 4,000 IU daily for approximately one year.	Drug: cholecalciferol; Enrolled subjects will supplement with vitamin D3 at 4,000 IU daily for one year; Other Name: vitamin D3

Outcome Measures

Primary Outcome Measures :

1. Change in transcriptional profiles after vitamin D supplementation. [ Time Frame: Scheduled prostate biopsy at baseline and repeat biopsy after 1 year ]
   RNA-sequencing analysis will be utilized to identify changes in transcriptional profiles and biological pathways in the prostate between African American and Caucasian men.

Secondary Outcome Measures :

1. Histopathology changes in the Gleason Score on repeat biopsy findings after vitamin D supplementation [ Time Frame: Scheduled prostate biopsy at baseline and repeat biopsy after 1 year ]

   The first reported finding in the pathology report is the Gleason Score. When the prostate sample is examined under the microscope, the Pathologist determines which type of cell is the most common and which type is the second most common. Each of these cell types is given a score from 1 to 5. Higher numbers mean more abnormal, aggressive cancer cells. Because the two most common types of cancer cells are identified, the Gleason Score is a combination of these two cell types. For example, the first most common cell type is a 3 and the second is reported as a 4, then the Gleason Score is 3+4, or 7.

   Changes to the baseline and repeat prostate biopsy Gleason Score will be analyzed.

2. Histopathology changes in the number of positive cores on repeat biopsy findings after vitamin D supplementation. [ Time Frame: Scheduled prostate biopsy at baseline and repeat biopsy after 1 year ]

   During a routine prostate biopsy, 12 core samples are collected: 2 samples from the top right, front and back, 2 from the top left, front and back; 2 from the middle right and 2 from the middle left; 2 from the bottom right and 2 from the bottom left. When the 12 cores are examined under the microscope, the Pathologist identifies which cores contain cancer cells (or are positive for cancer).

   Therefore, the pathology report will identify the number of positive cores between 0 to 12.

   Changes to the baseline and repeat prostate biopsy positive core will be analyzed.

3. Histopathology changes in the highest percentage of core involvement on repeat biopsy findings after vitamin D supplementation. [ Time Frame: Scheduled prostate biopsy at baseline and repeat biopsy after 1 year ]

   When the Pathologist examines the 12 core samples from the prostate biopsy, the percentage of cancer cells that are in each core is also identified. This can be from 0 to 100 percent involvement.

   To facilitate the evaluation of the 12 percentages reported for the 12 cores in the pathology report, the Urology standard is to prioritize and assess the highest percentage of core involvement.

   Changes to the baseline and repeat biopsy highest percentage core involvement will be analyzed.

4. Identify changes in molecular signature that exist in AA and Caucasian men in relation to vitamin D levels [ Time Frame: Scheduled prostate biopsies at baseline and after one year vit D supplementation plus allostatic load measurements at baseline and one yeat visits ]
   RNA-seq analyses of prostate tissue plus allostatic load measurements to determine stress response

Eligibility Criteria

• Ages Eligible for Study: 50 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: Male
• Gender Based Eligibility: Yes
• Gender Eligibility Description: Individuals having a prostate biopsy are eligible for recruitment.
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

Recruitment:

• scheduled for prostate biopsy
• permission for investigators to follow subject's post biopsy diagnosis, treatment decision and follow-up care (including subsequent prostate biopsies).

Enrollment:

• diagnosis of prostate cancer
• treatment recommendation or subject decision of Active Surveillance
• agreement to supplement with vitamin D3 4,000 IU daily for approximately one year
• standard of care repeat PSA at six months and surveillance prostate biopsy at one year

Exclusion Criteria:

• current vitamin D3 supplementation > 2,000 IU daily
• inability or unwillingness to continue to participate in the study

Contacts and Locations

Locations

United States, South Carolina

Ralph H. Johnson VA Medical Center

Charleston, South Carolina, United States, 29401

Sponsors and Collaborators

Medical University of South Carolina

Ralph H. Johnson VA Medical Center

National Institute on Minority Health and Health Disparities (NIMHD)

Investigators

• Study Director: Chanita Hughes-Halbert, PhD; MUSC Psychiatry and Behavioral Sciences

More Information

• Responsible Party: Stephen Savage, Professor, Medical University of South Carolina
• ClinicalTrials.gov Identifier: NCT04621500
• Other Study ID Numbers: 00085140; 5U54MD010706-03 ( U.S. NIH Grant/Contract )
• First Posted: November 9, 2020
• Last Update Posted: February 8, 2023
• Last Verified: January 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Vitamin D Deficiency; Fractures, Stress; Avitaminosis; Deficiency Diseases; Malnutrition; Nutrition Disorders; Fractures, Bone; Wounds and Injuries; Vitamin D; Cholecalciferol; Vitamins; Micronutrients; Physiological Effects of Drugs; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents