Clinical trial NCT01570309: Vitamin D Repletion in Coronary Artery Disease
Official title: The Effects of Vitamin D Repletion on Endothelial Function and Inflammation in Patients With Coronary Artery Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Vitamin D Deficiency
Coronary Artery Disease
Endothelial Dysfunction
Inflammation
Keywords: 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
Lead sponsor: New York City Health and Hospitals Corporation
Sponsor class: OTHER
Collaborators: name: American Heart Association
name: Jacobi Medical Center
name: Albert Einstein College of Medicine
name: Yale University
name: Montefiore Medical Center
First posted: 2012-04-04
Enrollment: 96
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Endothelial Function
timeFrame: Baseline and 12 weeks
measure: Inflammation -
timeFrame: Baseline and 12 weeks
measure: Inflammation
timeFrame: Baseline to 12 weeks
measure: Inflammation
timeFrame: Baseline to 12 weeks
measure: Inflammation
timeFrame: Baseline to week 12
Secondary outcomes:
Other outcomes:
Locations:
city: Bronx
country: United States
facility: Jacobi Medical Center
state: New York
city: Bronx
country: United States
facility: Montefiore Medical Center / Weiler division
state: New York
Study officials:
affiliation: Jacobi Medical Center
name: Seth I Sokol, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Sokol SI, Srinivas V, Crandall JP, Kim M, Tellides G, Lebastchi AH, Yu Y, Gupta AK, Alderman MH. The effects of vitamin D repletion on endothelial function and inflammation in patients with coronary artery disease. Vasc Med. 2012 Dec;17(6):394-404. doi: 10.1177/1358863X12466709.