Comparative Analysis of Immunological Responses to Vitamin D Replacement Therapy in Black and West African Men Diagnosed With Prostate Cancer: Elucidating Differential Effects on Immune Function Between Patients With Localized Disease and Those With Metastatic Progression

Overview

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.