This study is testing whether fixing vitamin D deficiency in Black/West African men with prostate cancer can strengthen their immune system, improve quality of life, and even slow cancer progression compared to those who remain deficient.

Key ideas being tested:

1. More than half of Black/West African prostate cancer patients don't have enough vitamin D.
2. Low vitamin D weakens immune cell function and affects quality of life, but these problems improve after 8 weeks of vitamin D supplements.
3. Immune cell function differs between patients with advanced/recurrent prostate cancer and those with localized disease.
4. Patients with advanced disease who show stronger immune responses after vitamin D correction may live longer without their PSA levels rising (a marker of cancer progression).
5. Immune cell function in Black/West African patients is different from that in Black/African American patients, and this will be checked by comparing data with a parallel Mayo Clinic study.

Overall goals:

1 . Measure how widespread vitamin D deficiency is in Black/West African prostate cancer patients.

2. Understand how vitamin D levels affect immunity and quality of life. 3. Compare immune function between different groups (localized vs. advanced disease, West African vs. African American patients).

4 . See if vitamin D replacement improves both patient well-being and cancer outcomes.

Study Flow

1. Recruitment & Consent: Patients with prostate cancer (localized or advanced) are invited and give written consent.

2 . Initial Blood Test (10 mL): Check vitamin D and calcium levels. 3. Eligibility: If vitamin D is low (<30 ng/mL), patients join the treatment phase.

4. Baseline Testing (50 mL blood + QOL survey): Immune function measured; quality of life survey completed; virtual doctor consult.

5. Treatment (8 weeks): Daily vitamin D3 pills (2000 IU, free); patients keep a medication diary.

6. Midpoint Check (Week 4): Phone call to check side effects and compliance. 7 .End of Treatment (Week 8): Repeat blood tests (60 mL), second QOL survey, virtual consult.

8. Follow up (up to 3 years). Annual phone calls and medical record review to track progression-free survival.

In short, the study is trying to show that vitamin D deficiency is common in Black/West African prostate cancer patients, that it harms immune function and quality of life, and that correcting it could improve both health and cancer survival.

Principal Investigators:

University of Ilorin, Ilorin, Nigeria: Ademola Alabi Popoola, MBBCH; Joshua Abiodun, PhD; Collaborators: Mayo Clinic, Jacksonville, Florida, USA: Gerardo Colon-Otero, MD, Trevanne Matthews-Hew, MD, Kim Barbel-Johnson, MD, Sandra Casanova, Keith L. Knutson,n PhD, For research laboratory tests that will be performed at the Mayo Clinic and planned retrospective comparisons with a parallel Mayo Clinic.

This clinical trial, designed to explore the potential role of vitamin D supplementation in improving outcomes among West African men with advanced prostate cancer, is grounded in the following hypothesis.

Clinical Trial Hypotheses Prevalence of Vitamin D Insufficiency More than half of Black/West African prostate cancer patients are expected to have vitamin D insufficiency.

Impact on Immune Function & Quality of Life Vitamin D insufficiency is associated with altered immune cell function and reduced health-related quality of life. Both are expected to improve after 8 weeks of vitamin D replacement.

Disease Stage Differences Immune cell function differs significantly between patients with metastatic/locally recurrent prostate cancer and those with localized disease.

PSA Progression-Free Survival Patients with metastatic or recurrent disease who show an improved immune response after vitamin D correction will have better PSA progression-free survival than those without immune response changes.

Comparisons Across Populations Immune cell function in Black/West African prostate cancer patients differs from that in Black/African American patients. This will be tested by comparing data from this study with a parallel Mayo Clinic study, both partially funded by the U.S. Department of Defense.

Study Aims & Purpose

• Evaluate the prevalence of vitamin D insufficiency among Black/West African prostate cancer patients.
• Assess immune deficits linked to vitamin D insufficiency.
• Compare immune cell function between Black/West African and Black/African American patients (via Mayo Clinic parallel study).
• Examine differences in immune function between localized vs. metastatic/recurrent disease.
• Determine whether vitamin D replacement improves quality of life and PSA progression-free survival (PSA-PFS).

Specific Objectives

• Measure the prevalence of vitamin D insufficiency in Black/West African prostate cancer patients.
• Analyze changes in immune cell function with insufficiency (<30 ng/ml) and after vitamin D replacement.
• Assess the acceptability of vitamin D replacement and its impact on health-related quality of life.
• Compare immune cell function between Black/West African vs. Black/African American patients, and between localized vs. advanced disease.
• Evaluate whether vitamin D replacement improves PSA-PFS in metastatic/recurrent patients who show immune response changes, compared to those without changes and historical controls.

Background Context

• Vitamin D insufficiency (hypovitaminosis D) is linked to increased risks of cardiovascular disease, cancer, infections, and overall mortality.
• Black populations are disproportionately affected due to melanin reducing skin vitamin D synthesis.
• Racial disparities in prostate cancer survival are influenced by socioeconomic, genetic, and health system factors.
• Vitamin D supplementation has been shown to reduce cancer mortality, improve progression-free survival in some cancers, and enhance quality of life.
• Immunological effects: Vitamin D modulates B-cells, T-cells, dendritic cells, and suppresses pro-tumor Th17 T cells, suggesting a role in cancer immunity.

Preliminary Data

• Mayo Clinic pilot study (Duval County, USA): 66% prevalence of hypovitaminosis D in African American participants.
• IRONMAN study (Nigeria): Over 150 men recruited, providing infrastructure for prostate cancer research.
• ICCARE Phase 1 Pilot Project 5: Serum vitamin D levels in 81 Nigerian prostate cancer patients vs. 71 controls showed significantly lower levels in cancer patients, especially advanced cases.
• These findings highlight the high prevalence of vitamin D insufficiency and its potential link to poor prostate cancer outcomes in Black/West African populations.

Study Design & Methods

• Type: Minimal-risk interventional clinical trial.
• Participants: Black/West African men with localized or metastatic/locally recurrent prostate cancer.
• Process:

Pre-screening: Serum vitamin D and calcium testing. Patients with vitamin D <30 ng/ml will be enrolled in the therapeutic arm. Intervention: Oral vitamin D3 (2000 IU daily, free of charge) for 8 weeks. Monitoring: Medication diary, 4-week phone check, baseline, and 8-week blood draws for immune function tests.

Quality of life: CDC HRQOL-4 survey at baseline and 8 weeks. Follow-up: Annual contact up to 3 years for PSA progression-free survival (PSA-PFS).

Study Aims (Detailed)

• Vitamin D Levels: Measure prevalence and mean/median serum 25OHD levels; assess immune regulation after supplementation.
• Immune Profiling: Phenotype immune cell populations (CD4, CD8, B cells, monocytes, dendritic cells, Tregs, NK cells).
• Cancer Antigen Immunity: Measure T-cell and antibody responses to prostate cancer antigens (PAP, PMSA, P53, MUC1).
• General Immunity: Assess responses to viral/bacterial antigens (e.g., tetanus, EBV, CMV).
• Clinical Outcomes: Evaluate PSA-PFS compared to historical controls and stratify by immune response changes after vitamin D replacement.

Target Accrual

• Pre-screening: 200 Nigerian men with localized prostate cancer and 200 with metastatic/locally recurrent disease.
• Intervention: ~100 localized and ~100 advanced cases (due to 60-70% prevalence of vitamin D insufficiency).
• Sample size: Adequate to evaluate effects of vitamin D insufficiency and replacement on immune profiles.

Subject Population

• Adults ≥18 years, Nigerians, with a history of prostate cancer (localized or advanced).
• Intervention group: 200 patients with low vitamin D (<30 ng/ml), treated with oral vitamin D3 (2000 IU daily for 8 weeks).
• Blood samples collected at UITH, Ilorin, Nigeria.

Specimen Handling

• Blood stored at -80°C freezers at the University of Ilorin.
• Shipped to Mayo Clinic Biobank and analyzed at Dr. Keith Knutson's lab (Florida).
• Retrospective comparison planned with Mayo Clinic parallel study (DoD-funded).

Data Analysis Plan

• Regression models controlling for age, BMI, smoking, and vitamin D receptor variants.
• Descriptive analysis of vitamin D supplement use (diagnosis, enrollment, follow-up).
• Frequency of vitamin D testing pre- and post-enrollment; chi-square and t-tests for group comparisons.
• Separate analyses for USA vs. Nigeria cohorts; centralized lab analysis at Mayo Clinic.

Endpoints

• Effects of vitamin D replacement on immune cell function.
• Differences in immune profiles:
• Black/African American vs. Black/West African patients.
• Localized vs. metastatic/recurrent disease.
• Antigen-specific T-cell and antibody responses (baseline vs. 8 weeks).
• Prevalence of vitamin D insufficiency.
• Acceptability of vitamin D replacement therapy.
• PSA progression-free survival (PSA-PFS) outcomes. Safety & Monitoring
• Vitamin D dose (2000 IU daily) is safe and within recommended limits.
• Adverse events monitored via phone calls and physician consults.
• Oversight by Savante Consulting (CRO), site PIs, and NAFDAC compliance.
• Clinical Monitoring Plan ensures GCP adherence and regulatory compliance. Data Storage & Access
• Patient data limited to essentials, stored securely in REDCap®.
• Hard copies locked for 5 years, then shredded.
• De-identified data sent to Mayo Clinic biostatisticians for analysis. Funding
• Supported by U.S. Department of Defense (DoD) (Project ID: PC230672P11).
• Covers investigator salaries, coordinators, lab supplies, pharmacy costs, and specimen processing.

Inclusion Criteria:

• Self-identified Black/West African Males, Age ≥18 years
• Patients with a previous history of localized or metastatic or locally recurrent prostate cancer
• Willing to travel to the University of Ilorin Surgery Outpatient Department (SOPD UITH)for baseline and 8 weeks visit for blood collection, if eligible.

Exclusion Criteria:

• Known hypersensitivity to vitamin D.
• End-stage renal failure on dialysis
• Liver cirrhosis
• Currently taking a vitamin D or multivitamin supplement, which has more than 400 IU/10mcg of vitamin D daily for the past month.
• Legal inability or restricted legal ability, medical or psychological conditions not allowing proper study completion or informed consent signature.
• History of hypercalcemia

The data arising from this study will be compared with a similar clinical trial taking place among African Americans in the USA

September 2027 for three years

The PI of the parrallel clinical trial taking place in Mayo Clinic, Jacksonville, Dr. Colon-Otero and those that he delegates will be able to access through RedCap