Vitamin D Repletion in Coronary Artery Disease

Seth I. Sokol, M.D.

Status: Completed

Conditions: Coronary Artery Disease; Inflammation; Endothelial Dysfunction; Vitamin D Deficiency

Treatments: Drug: Ergocalciferol; Other: Sugar pill

Study type: Interventional

Funder types: Other

Identifiers

NCT01570309

AHA Award #0885041N

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 96 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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96 participants in 2 patient groups, including a placebo group

Ergocalciferol

Active Comparator group

Description:

50,000 units of ergocalciferol once a week for 12 weeks

Treatment:

Drug: Ergocalciferol

Sugar pill

Placebo Comparator group

Treatment:

Other: Sugar pill