Vitamin D Repletion in Coronary Artery Disease

This study has been completed.
Sponsor:
Collaborators:
American Heart Association
Jacobi Medical Center
Albert Einstein College of Medicine of Yeshiva University
Yale University
Montefiore Medical Center
Information provided by (Responsible Party):
Seth I. Sokol, M.D., New York City Health and Hospitals Corporation
ClinicalTrials.gov Identifier:
NCT01570309
First received: March 26, 2012
Last updated: August 5, 2013
Last verified: August 2013
  Purpose

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.


Condition Intervention
Vitamin D Deficiency
Coronary Artery Disease
Endothelial Dysfunction
Inflammation
Drug: Ergocalciferol
Other: Sugar pill

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: The Effects of Vitamin D Repletion on Endothelial Function and Inflammation in Patients With Coronary Artery Disease

Resource links provided by NLM:


Further study details as provided by New York City Health and Hospitals Corporation:

Primary Outcome Measures:
  • Endothelial Function [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]
    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.

  • Inflammation - [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]
    Median within subject change in hs-CRP levels between baseline and week 12 in active and placebo groups

  • Inflammation [ Time Frame: Baseline to 12 weeks ] [ Designated as safety issue: No ]
    Median within subject change in interferon-gamma levels between baseline and week 12 in active and placebo groups

  • Inflammation [ Time Frame: Baseline to 12 weeks ] [ Designated as safety issue: No ]
    Median within subject change in cxcl-10 .levels between baseline and week 12 in active and placebo groups

  • Inflammation [ Time Frame: Baseline to week 12 ] [ Designated as safety issue: No ]
    Median within subject change in IL-12 levels between baseline and week 12 in active and placebo groups


Enrollment: 96
Study Start Date: August 2008
Study Completion Date: March 2011
Primary Completion Date: March 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Ergocalciferol
50,000 units of ergocalciferol once a week for 12 weeks
Drug: Ergocalciferol
Oral capsule, 50,000 units, once a week, 12 weeks
Placebo Comparator: Sugar pill Other: Sugar pill
Oral capsule, once a week, 12 weeks

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01570309

Locations
United States, New York
Jacobi Medical Center
Bronx, New York, United States, 10461
Montefiore Medical Center / Weiler division
Bronx, New York, United States, 10461
Sponsors and Collaborators
Seth I. Sokol, M.D.
American Heart Association
Jacobi Medical Center
Albert Einstein College of Medicine of Yeshiva University
Yale University
Montefiore Medical Center
Investigators
Principal Investigator: Seth I Sokol, MD Jacobi Medical Center
  More Information

Publications:
Responsible Party: Seth I. Sokol, M.D., Principal Investigator, New York City Health and Hospitals Corporation
ClinicalTrials.gov Identifier: NCT01570309     History of Changes
Other Study ID Numbers: AHA Award #0885041N
Study First Received: March 26, 2012
Results First Received: September 23, 2012
Last Updated: August 5, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by New York City Health and Hospitals Corporation:
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

Additional relevant MeSH terms:
Coronary Artery Disease
Myocardial Ischemia
Coronary Disease
Inflammation
Vitamin D Deficiency
Heart Diseases
Cardiovascular Diseases
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Pathologic Processes
Avitaminosis
Deficiency Diseases
Malnutrition
Nutrition Disorders
Ergocalciferols
Vitamin D
Vitamins
Bone Density Conservation Agents
Physiological Effects of Drugs
Pharmacologic Actions
Micronutrients
Growth Substances

ClinicalTrials.gov processed this record on July 20, 2014