Optimization of Blood Levels of 25(OH)-Vitamin D in African Americans

Study Overview
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Brief Summary
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Two-thirds of the US population, particularly African Americans (AA), is at risk for inadequate or deficient 25-hydroxy-vitamin D (25(OH)VD). Epidemiological studies demonstrate an association between better health outcomes and higher blood levels of 25(OH)VD . Randomized controlled clinical trials have shown that, while supraphysiological high doses of VD are needed to achieve adequate blood levels of 25(OH)VD, not all subjects respond to them. Recent studies have also questioned the therapeutic effects of high-dose VD supplementation. Severe VD deficiency has been associated independently with the future risk of mild cognitive impairment (MCI) and dementia. A reduction in GSH and an increase in the oxidative stress levels of serum, erythrocytes, and circulating lymphocytes has been observed in MCI and Alzheimer disease, findings similar to those in VD deficient persons. Scholarly reviews conclude that excess oxidative stress is one of the major risk factors for AD and support a potential therapeutic role for L-cysteine (LC, a GSH precursor) and vitamin D (VD) supplementation in the treatment of Alzheimer disease symptoms. This application presents the investigators' design for a randomized, double-blind, placebo-controlled clinical trial to test the hypothesis that supplementation with VD in combination with L-cysteine (LC) is more successful at optimizing the statuses of 25(OH)VD [biological signatures] and simultaneously decreasing TNF-α, IR [functional or clinical outcomes], and oxidative stress, suggesting a better therapeutic approach compared with supplementation with VD alone in AA subjects.

Official Title
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Optimization of Blood Levels of 25(OH)-Vitamin D in African Americans

Conditions
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Vitamin D Deficiency

Intervention / Treatment
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* Drug: Vitamin D
* Drug: Placebo
* Drug: Vitamin D + L-cysteine
* Drug: L-cysteine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: African American volunteers only Participants between the ages of 18 and 65 Must be In good general health Women with negative pregnancy tests Exclusion Criteria: Subjects with Diabetes, Heart disease, Sickle Cell disease, or Epilepsy Subjects with serum positive pregnancy test or breastfeeding

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Initially, all of the study subjects will be provided placebo supplementation as a placebo run-in period for one month before randomization. The placebo run-in period is meant to stabilize subjects in the study and will prevent any effect due solely to inclusion in the study. Placebo and supplement capsules will be similar in appearance, taste, texture, and smell, and will be provided by the pharmacist, who will have the codes for which subjects are assigned to which supplement or placebo. During testing, the placebo group will take two placebo capsules a day in the morning. Supplements will be taken daily with food at breakfast for 6 months, while participants continue to carry on a normal lifestyle | Drug: Placebo<br>* Capsule ingested orally<br>* Other names: starch;|
| Experimental: L-Cysteine<br>LC group will receive two capsules of LC daily. Supplements will be taken daily with food at breakfast for 6 months, while participants continue to carry on a normal lifestyle | Drug: L-cysteine<br>* Capsule ingested orally<br>* Other names: amino acid;|
| Experimental: Vitamin D3<br>VD group will take two capsules and each capsule will contain 1000 IU VD daily. Supplements will be taken daily with food at breakfast for 6 months, while participants continue to carry on a normal lifestyle | Drug: Vitamin D<br>* Capsules ingested orally<br>* Other names: cholecalciferol;|
| Experimental: Vitamin D3 and L-Cysteine<br>VD+LC group will take daily two capsule containing 1000 IU+500 mg LC. Supplements will be taken daily with food at breakfast for 6 months, while participants continue to carry on a normal lifestyle | Drug: Vitamin D + L-cysteine<br>* Capsule ingested orally<br>* Other names: combination of vitamin D and L-cysteine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 25-hydroxy-vitamin D | Change in blood levels of 25(OH)VD | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| TNF-α | Whether any increase in vitamin D beneficially decreases insulin resistance | 6 months | 
| HOMA-IR | Whether any decrease in TNF-a beneficially decreases insulin resistance | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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African American;, Vitamin D;, Insulin resistance, Alzheimer's Disease