Impact of Vitamin D Supplementation on Cardiac Structure and Function

Study Overview
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Brief Summary
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The VITamin D and OmegA-3 TriaL (VITAL; NCT 01169259) is a randomized clinical trial in 20,000 U.S. men and women investigating whether taking daily dietary supplements of vitamin D3 (2000 IU) or fish oil (1 gram of omega-3 fatty acids) reduces the risk of developing cancer, heart disease, and stroke in people who do not have a prior history of these illnesses. This ancillary study (VITAL-Echo) is being conducted among participants in VITAL and will examine whether vitamin D compared to placebo: (1) reduces left ventricular (LV) mass in elderly individuals as measured with 2-dimensional echocardiography and (2) improves LV systolic and diastolic function as measured with tissue Doppler echocardiography.

Detailed Description
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Recognition of the biological effects of vitamin D on cardiovascular function has been growing. The main objective of the parent trial (VITAL) is to evaluate the effects of vitamin D on cardiac events but is focused on atherothrombotic events and does not specifically address vitamin D effects on LV mass. In ambulatory individuals, LV mass is a key cardiac structural feature and increases in LV mass are frequently accompanied by diastolic dysfunction. This study leverages the existing infrastructure of the parent VITAL trial to perform cardiac imaging studies on a subset of subjects who will be randomized to vitamin D3 (n=500) or placebo (n=500). Echocardiography is a noninvasive, widely accessible tool to evaluate cardiac structure and function. Cardiac echo imaging visits will take place at baseline (pre-randomization), and then after 2 years, at the Massachusetts General Hospital (MGH). The acronym VITAL-Echo reflects the link to the parent VITAL trial and an ancillary investigation of vitamin D versus placebo on LV mass and function as measured by echocardiography. The effect of fish oil supplementation on these parameters will be evaluated as a secondary endpoint, thereby taking advantage of the factorial design of the parent trial.

Official Title
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Vitamin D and Omega-3 Trial: Ancillary Study (VITAL-Echo) on the Impact of Vitamin D Supplementation on Cardiac Structure and Function

Conditions
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Cardiovascular Disease

Intervention / Treatment
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* Dietary Supplement: Vitamin D3 + fish oil/fish oil placebo
* Dietary Supplement: Vitamin D3 placebo + fish oil/fish oil placebo


Participation Criteria
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Eligibility Criteria
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Participants in VITAL (NCT 01169259) who meet the following criteria are eligible to participate in this ancillary study: Inclusion: Willingness to participate in ancillary study of VITAL to undergo cardiac echocardiography (baseline and at 3 years) and sign informed consent to participate in the ancillary study Live in the greater Boston area (within 60 miles of MGH) Exclusion: Have a pacemaker, prosthetic valve(s), surgical wires or other devices that could alter the echocardiographic image findings.

Ages Eligible for Study
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Minimum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Vitamin D3 + fish oil/placebo<br>Vitamin D3 2000 IU/day and fish oil (840 omega 3-fatty acids; Omacor)(or fish oil placebo)/day | Dietary Supplement: Vitamin D3 + fish oil/fish oil placebo<br>* Vitamin D3 2000 IU/day and fish oil (840 mg of omega 3-fatty acids; Omacor)/fish oil placebo per day<br>* Other names: Omacor;|
| Placebo Comparator: Vitamin D3 placebo + fish oil/placebo<br>Vitamin D3 placebo + fish oil (840 mg of omega 3-fatty acids; Omacor)/fish oil placebo | Dietary Supplement: Vitamin D3 placebo + fish oil/fish oil placebo<br>* Vitamin D3 placebo/day + fish oil (840 mg of omega 3-fatty acids; Omacor)/fish oil placebo/day<br>* Other names: Omacor;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in left ventricular (LV) mass | Primary aim is to examine whether vitamin D supplementation reduces LV mass in elderly individuals, using 2-dimensional echocardiography. | Baseline and 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in LV systolic/diastolic function | LV systolic and diastolic function using tissue Doppler echocardiography (2 D Echo will be used to measure ejection fraction in systole; E wave, E' E deceleration time, pulmonary vein inflow patterns in diastole; tissue doppler will measure S' in systole and E' in diastole; Speckle tracking will measure global longitudinal strain, LV torsion in systole and oeak LV untwisting rate in diastole). | Baseline and 2 years | 
| Change in LV mass | To examine whether vitamin D supplementation with/without fish oil supplementation reduces LV mass in elderly individuals, using 2-dimensional echocardiography. | Baseline and 2 years | 
| Change in LV systolic/diastolic function | Effect of Vitamin D with/without fish-oil on LV systolic and diastolic function using tissue Doppler echocardiography (as above). | Baseline and 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Vitamin D3, Left ventricular mass, Echocardiography, Left ventricular systolic and diastolic function