Vitamin D Repletion in Coronary Artery Disease

• Sponsor: Seth I. Sokol, M.D. (Other)
• Overall Status: Completed
• CT.gov ID: NCT01570309
• Collaborator: American Heart Association (Other), Jacobi Medical Center (Other), Albert Einstein College of Medicine (Other), Yale University (Other), Montefiore Medical Center (Other)
• Enrollment: 96
• Locations: 2
• Arms: 2
• Duration (Months): 30.9
• Patients Per Site: 48
• Patients Per Site Per Month: 1.6

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Vitamin D Deficiency; Coronary Artery Disease; Endothelial Dysfunction; Inflammation	Drug: Ergocalciferol; Other: Sugar pill	N/A

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 96 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, 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
• Study Start Date: Aug 1, 2008
• Actual Primary Completion Date: Mar 1, 2011
• Actual Study Completion Date: Mar 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
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

Outcome Measures

Primary Outcome Measures

1. Endothelial Function [Baseline and 12 weeks]

   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.

2. Inflammation - [Baseline and 12 weeks]

   Median within subject change in hs-CRP levels between baseline and week 12 in active and placebo groups

3. Inflammation [Baseline to 12 weeks]

   Median within subject change in interferon-gamma levels between baseline and week 12 in active and placebo groups

4. Inflammation [Baseline to 12 weeks]

   Median within subject change in cxcl-10 .levels between baseline and week 12 in active and placebo groups

5. Inflammation [Baseline to week 12]

   Median within subject change in IL-12 levels between baseline and week 12 in active and placebo groups

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Locations

	Site	City	State	Country	Postal Code
1	Jacobi Medical Center	Bronx	New York	United States	10461
2	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
• Yale University
• Montefiore Medical Center

Investigators

• Principal Investigator: Seth I Sokol, MD, Jacobi Medical Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Seth I. Sokol, M.D., Principal Investigator, New York City Health and Hospitals Corporation
• ClinicalTrials.gov Identifier: NCT01570309
• Other Study ID Numbers: AHA Award #0885041N
• First Posted: Apr 4, 2012
• Last Update Posted: Oct 10, 2013
• Last Verified: Aug 1, 2013

• Keywords provided by Seth I. Sokol, M.D., Principal Investigator, 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; Vitamin D Deficiency; Inflammation; Ergocalciferols; Vitamin D

Study Results

Participant Flow

Recruitment Details	Recruitment from October 2008 through December 2010 from the cardiac catheterization laboratories and outpatient clinics of the Jacobi Medical Center and Montefiore Medical Center in the Northeastern section of the Bronx, NY. Additional recruitment occurred at Crystal Run Health in Orange County, NY.
Pre-assignment Detail	Subjects with ≥ 50% angiographic stenosis of at least 1 coronary artery or documented previous revascularization, were screened for vitamin D deficiency by measurement of serum 25-hydroxyvitamin D (25-vitamin D).Eligible subjects with a 25-vitamin D level < 20 ng/ml were randomly assigned 1:1 to active or placebo treatment

Arm/Group Title	Ergocalciferol	Sugar Pill
Arm/Group Description	50,000 units of ergocalciferol once a week for 12 weeks	Matching placebo
Period Title: Overall Study
STARTED	48	48
COMPLETED	45	45
NOT COMPLETED	3	3

Baseline Characteristics

Arm/Group Title	Ergocalciferol	Sugar Pill	Total
Arm/Group Description	50,000 units of ergocalciferol once a week for 12 weeks	Matching placebo	Total of all reporting groups
Overall Participants	48	48	96
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	43 89.6%	35 72.9%	78 81.3%
>=65 years	5 10.4%	13 27.1%	18 18.8%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	54.6 (9.5)	56.5 (11.7)	55.6 (10.6)
Sex: Female, Male (Count of Participants)
Female	9 18.8%	15 31.3%	24 25%
Male	39 81.3%	33 68.8%	72 75%
Region of Enrollment (participants) [Number]
United States	48 100%	48 100%	96 100%

Outcome Measures

1. Primary Outcome

Title	Endothelial Function
Description	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.
Time Frame	Baseline and 12 weeks

Outcome Measure Data

Analysis Population Description

Assuming a standard deviation of 0.6 in the change in RH-PAT score from baseline to 12 weeks, we estimated that the study would need a sample size of 45 patients per treatment group to have 80% power at a two tailed alpha=0.05 level to detect a minimum difference in change in RH-PAT score of 0.36 between treatment groups.

Arm/Group Title	Ergocalciferol	Sugar Pill
Arm/Group Description	50,000 units of ergocalciferol once a week for 12 weeks	Matching placebo
Measure Participants	45	45
Median (Inter-Quartile Range) [reactive hypermia index]	0.13	-0.04

2. Primary Outcome

Title	Inflammation -
Description	Median within subject change in hs-CRP levels between baseline and week 12 in active and placebo groups
Time Frame	Baseline and 12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Active	Sugar Pill
Arm/Group Description	Ergocalciferal 50,000 U qweekly x 12 weeks	Matching Placebo
Measure Participants	45	45
Median (Inter-Quartile Range) [mg/dl]	-0.17	-0.05

3. Primary Outcome

Title	Inflammation
Description	Median within subject change in interferon-gamma levels between baseline and week 12 in active and placebo groups
Time Frame	Baseline to 12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ergocalciferol	Sugar Pill
Arm/Group Description	50,000 units of ergocalciferol once a week for 12 weeks	Matching placebo
Measure Participants	45	45
Median (Inter-Quartile Range) [pg/ml]	-2.29	-2.8

4. Primary Outcome

Title	Inflammation
Description	Median within subject change in cxcl-10 .levels between baseline and week 12 in active and placebo groups
Time Frame	Baseline to 12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Active Therapy	Placebo
Arm/Group Description	Ergocalciferol 50,000 U q weekly x 12 weeks	Sugar Pill
Measure Participants	45	45
Median (Inter-Quartile Range) [pg/ml]	-7.45	-2.72

5. Primary Outcome

Title	Inflammation
Description	Median within subject change in IL-12 levels between baseline and week 12 in active and placebo groups
Time Frame	Baseline to week 12

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ergocalciferol	Sugar Pill
Arm/Group Description	50,000 units of ergocalciferol once a week for 12 weeks	Matching placebo
Measure Participants	45	45
Median (Inter-Quartile Range) [pg/ml]	-10.96	-2.33

Adverse Events

Arm/Group Title	Ergocalciferol		Sugar Pill
Arm/Group Description	50,000 units of ergocalciferol once a week for 12 weeks		Matching placebo
All Cause Mortality
	Ergocalciferol		Sugar Pill
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Ergocalciferol		Sugar Pill
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	10/45 (22.2%)		9/45 (20%)
Cardiac disorders
Death	1/45 (2.2%)	1	0/45 (0%)	0
Heart failure exacerbation	0/45 (0%)	0	1/45 (2.2%)	1
Syncope	1/45 (2.2%)	1	0/45 (0%)	0
ICD shock inappropriate	1/45 (2.2%)	1	0/45 (0%)	0
Angina	0/45 (0%)	0	3/45 (6.7%)	3
Atypical chest pain	1/45 (2.2%)	1	2/45 (4.4%)	2
Gastrointestinal disorders
Gastric ulcer	0/45 (0%)	0	1/45 (2.2%)	1
Constipation	1/45 (2.2%)	1	0/45 (0%)	0
Infections and infestations
Urinary tract infection	1/45 (2.2%)	1	0/45 (0%)	0
Injury, poisoning and procedural complications
Trauma	1/45 (2.2%)	1	0/45 (0%)	0
Metabolism and nutrition disorders
Hyperkalemia	1/45 (2.2%)	1	0/45 (0%)	0
Gout	1/45 (2.2%)	1	0/45 (0%)	0
Musculoskeletal and connective tissue disorders
Musculoskeletal pain	0/45 (0%)	0	1/45 (2.2%)	1
Renal and urinary disorders
Hematuria	0/45 (0%)	0	1/45 (2.2%)	1
Respiratory, thoracic and mediastinal disorders
Asthma exacerbation	1/45 (2.2%)	1	0/45 (0%)	0
Other (Not Including Serious) Adverse Events
	Ergocalciferol		Sugar Pill
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/45 (8.9%)		4/45 (8.9%)
General disorders
Headache	4/45 (8.9%)		4/45 (8.9%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.