Prostate Cancer, Stress Reaction, Vitamin D Deficiency
Conditions
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 will 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/inflammatory markers) will also be collected at the time of enrollment and at the repeat prostate biopsy visit.
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 (inflammatory markers) plus a Vitamin D level, will be collected. Vitamin D3 soft gels (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 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.
Interventions
DRUGcholecalciferol
Enrolled subjects will supplement with vitamin D3 at 4,000 IU daily for one year
PROCEDUREStandard of Care Prostate Biopsy - collection of 13th core for RNA-seq
RNA-seq analysis will be used to (a) identify changes in transcriptional profiles and biological pathways in the prostate between African American and Caucasian men and (b) compare Allostatic Load results to determine stress response and (c) identify changes in the molecular signature in relation to vitamin D levels
PROCEDUREStandard of Care Prostate Biopsies at baseline and after one year vitamin D3 supplementation
Pathology results of the prostate biopsies will be analyzed for changes in the (a) Gleason Score (b) the number of positive cores (0 to 12) and (c) the highest percentage of positive core involvement (0 to 100%).
DIAGNOSTIC_TESTAllostatic Load
Diagnostic Test: Allostatic Load Measurements at baseline and after one year vitamin D3 supplementation Allostatic Load measurements to determine body stress compared at baseline and after one year of vitamin D3 supplementation. Also compared with RNA-seq results to determine stress response. Other Names: Bloodwork for HgbA1c, lipid profile, creatinine, albumin and vitamin D levels. Body measurements: Ht. Wt, BMI, waist and hip measurements for waist/hip ratio. Measurements of systolic and diastolic blood pressure and heart rate
Sponsors
Ralph H. Johnson VA Medical Center
National Institute on Minority Health and Health Disparities (NIMHD)
Medical University of South Carolina
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Intervention model description
Single, open-label group
Eligibility
Sex/Gender
MALE
Age
50 Years to 75 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Change in Transcriptional Profiles After Vitamin D Supplementation. | 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
| Measure | Time frame | Description |
|---|---|---|
| Median Percentage of Positive Cores at 1-year Post-baseline | 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. |
| Identify Changes in Molecular Signature That Exist in AA and Caucasian Men in Relation to Vitamin D Levels | 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 |
Countries
United States
Participant flow
Recruitment details
Patients were recruited in the urology clinic at the Ralph H. Johnson VAMC. All patients who were eligible for active surveillance for prostate cancer were offered enrollment and were followed at the same location. They were recruited from 6/4/19 until 2/4/22
Participants by arm
| Arm | Count |
|---|---|
| Open Label All enrolled subjects will receive vitamin D3 at 4,000 IU daily for approximately one year.
cholecalciferol: Enrolled subjects will supplement with vitamin D3 at 4,000 IU daily for one year
Standard of Care Prostate Biopsy - collection of 13th core for RNA-seq: RNA-seq analysis will be used to (a) identify changes in transcriptional profiles and biological pathways in the prostate between African American and Caucasian men and (b) compare Allostatic Load results to determine stress response and (c) identify changes in the molecular signature in relation to vitamin D levels
Standard of Care Prostate Biopsies at baseline and after one year vitamin D3 supplementation: Pathology results of the prostate biopsies will be analyzed for changes in the (a) Gleason Score (b) the number of positive cores (0 to 12) and (c) the highest percentage of positive core involvement (0 to 100%). | 60 |
| Total | 60 |
Baseline characteristics
| Characteristic | Open Label |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 31 Participants |
| Age, Categorical Between 18 and 65 years | 29 Participants |
| Age (years) | 65 years |
| Body Mass Index (BMI) | 29.2 Measured in kilograms per meters squared |
| HbA1c level% | 5.6 Percentage |
| psa (mcg/l) | 6.21 micrograms per liter |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 33 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 27 Participants |
| Region of Enrollment United States | 60 Participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 60 Participants |
| Total cholesterol (mg/dl) | 189 milligrams per deciliter |
| Vitamin D (ng/ml) | 28 nanograms per milliliter |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 60 |
| other Total, other adverse events | 0 / 60 |
| serious Total, serious adverse events | 0 / 60 |
Outcome results
Primary
Percentage of Participants With Change in Transcriptional Profiles After Vitamin D Supplementation.
RNA-sequencing analysis will be utilized to identify changes in transcriptional profiles and biological pathways in the prostate between African American and Caucasian men.
Time frame: Scheduled prostate biopsy at baseline and repeat biopsy after 1 year
Population: We analyzed all subjects and compared initial biopsy results and RNA sequencing information at baseline and after supplemental vitamin D3 one year later. We looked at modifications of signaling pathways from baseline and after treatment and also compared African-Americans vs. Caucasions
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Open Label | Percentage of Participants With Change in Transcriptional Profiles After Vitamin D Supplementation. | 100 percentage of subjects |
Secondary
Identify Changes in Molecular Signature That Exist in AA and Caucasian Men in Relation to Vitamin D Levels
RNA-seq analyses of prostate tissue plus allostatic load measurements to determine stress response
Time frame: Scheduled prostate biopsies at baseline and after one year vit D supplementation plus allostatic load measurements at baseline and one yeat visits
Population: Number of positive cores per patient on a standard prostate biopsy involving systematic sampling of the prostate.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Open Label | Identify Changes in Molecular Signature That Exist in AA and Caucasian Men in Relation to Vitamin D Levels | 17.4 number of positive cores |
Secondary
Median Percentage of Positive Cores at 1-year Post-baseline
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.
Time frame: Scheduled prostate biopsy at baseline and repeat biopsy after 1 year
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Open Label | Median Percentage of Positive Cores at 1-year Post-baseline | 0.5 percentage of positive cores |