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

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.

• Tolerability of eight weeks of Vitamin D supplementation in African men with Advanced Prostate Cancer who have low levels of Vitamin D [Срок оценки: Tolerability will be monitored during the 8-week supplementation period and for an additional 8 weeks thereafter, covering a total duration of 16 weeks.]
• Vitamin D supplementation and PSA levels in advanced prostate cancer. [Срок оценки: The PSA will be measured every three months for each patient 36 months]
• Vitamin D supplementation and immune cell activity in advanced prostate cancer. [Срок оценки: The immune cell counts will be measured at the recruitment after 8 weeks]