Vitamin D Repletion in Coronary Artery Disease

Study Overview
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Brief Summary
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Vitamin D (Vit D) status is an emerging risk marker of great interest in cardiovascular disease (CVD). Lower serum levels of Vit D are associated with both cardiac risk factors and prevalent cardiovascular disease. Vit D insufficiency remains very prevalent in free living populations in the United States especially in urban, and multi-ethnic low income Northern cities.To date, prospective randomized trials using Vit D supplementation to modify CVD risk and evaluate outcomes have not been performed. The investigators propose a double-blind, randomized wait-list control trial in subjects with Coronary Artery Disease (CAD) and Vit D deficiency with two specific aims. Specific aim 1 is to measure endothelial function using reactive hyperemia peripheral arterial tonometry (RH-PAT) before and after treatment with Vit D replacement therapy. Specific Aim 2 is to measure levels of inflammation before and after treatment with Vit D replacement therapy. These aims will test the hypotheses that Vit D repletion will improve endothelial function and reduce the levels of detectable inflammation in the plasma of these subjects.

Detailed Description
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100 subjects with angiographically documented CAD and Vit D deficiency will be randomized to 50,000 IU oral ergocalciferol (active treatment group) or placebo (delayed intervention group) once a week for 12 weeks. The investigators will measure endothelial function at randomization and week 12 using RH-PAT and serologically measured adhesion molecules (s-VCAM, s-ICAM, soluble e-selectin). Changes in levels of plasma cytokines and chemokines representing a T-cell activation pathway (IL-12, IFN-g and CXCL-10 - IFN-g axis) the investigators have linked to coronary atherogenesis (independent of CRP) and poor CV outcomes, will be measured over the 12 week study period. Given published evidence showing that Vit D can influence this T- cell pathway, specific aim 2 will add mechanistic insights to this proposal. High sensitivity C-reactive protein (hs-CRP) will be measured as it is a well established traditional marker of inflammation in CAD and has also been linked to Vit D status.

Official Title
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The Effects of Vitamin D Repletion on Endothelial Function and Inflammation in Patients With Coronary Artery Disease

Conditions
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Coronary Artery Disease, Vitamin D Deficiency, Endothelial Dysfunction, Inflammation

Intervention / Treatment
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* Drug: Ergocalciferol
* Other: Sugar pill


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and nonpregnant females greater than 18 years of age ≥ 50% angiographic stenosis of at least 1 coronary artery or documented previous revascularization Serum 25-hydroxyvitamin D < 20 ng/ml Exclusion Criteria: confinement to a nursing facility, institution or home GFR < 60 ml/min (by MDRD equation) presence of liver disease hypercalcemia NYHA class III or IV heart failure cardiogenic shock at time of presentation current planned or emergent CABG prior gastric or small bowel surgery pancreatitis malabsorption inflammatory bowel disease autoimmune disease active malignancy current use of > 800 IU/day of vitamin D Current use of dilantin, phenobarbitol, immunosuppressant, or immunostimulant therapy

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

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 |
| --- | --- |
| Active Comparator: Ergocalciferol<br>50,000 units of ergocalciferol once a week for 12 weeks | Drug: Ergocalciferol<br>* Oral capsule, 50,000 units, once a week, 12 weeks<br>|
| Placebo Comparator: Sugar pill<br> | Other: Sugar pill<br>* Oral capsule, once a week, 12 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Endothelial Function | Endothelial function was measured using peripheral arterial tonometry expressed as the reactive hyperemia index. The index is derived from the ratio of the post-to-pre occlusion peripheral arterial tonometry signal amplitude of the tested arm, divided by the post -to-pre occlusion ratio of the control arm. Median within subject change in endothelial function as measured by reactive hyperemia peripheral arterial tonometry index in each group is presented. | Baseline and 12 weeks | 
| Inflammation - | Median within subject change in hs-CRP levels between baseline and week 12 in active and placebo groups | Baseline and 12 weeks | 
| Inflammation | Median within subject change in interferon-gamma levels between baseline and week 12 in active and placebo groups | Baseline to 12 weeks | 
| Inflammation | Median within subject change in cxcl-10 .levels between baseline and week 12 in active and placebo groups | Baseline to 12 weeks | 
| Inflammation | Median within subject change in IL-12 levels between baseline and week 12 in active and placebo groups | Baseline to week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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vitamin D,, vitamin D deficiency, coronary artery disease, ergocalciferol, endothelial function, adhesion molecules, inflammation, IL-12, interferon-gamma, CXCL-10, reactive hyperemia peripheral arterial tonometry, endothelial dysfunction, cytokines, chemokines