Impact of Vitamin D Supplementation on Cardiac Structure and Function (VITAL-Echo)

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

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.

Study Overview

• Status: Completed
• Conditions: Cardiovascular Disease
• Intervention / Treatment: Dietary supplement: Vitamin D3 + fish oil/fish oil placebo; Dietary supplement: Vitamin D3 placebo + fish oil/fish oil placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 1025
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Vitamin D3 + fish oil/placebo; 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; Vitamin D3 2000 IU/day and fish oil (840 mg of omega 3-fatty acids; Omacor)/fish oil placebo per day; Other Names: Cholecalciferol; Omacor
Placebo Comparator: Vitamin D3 placebo + fish oil/placebo; 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; Vitamin D3 placebo/day + fish oil (840 mg of omega 3-fatty acids; Omacor)/fish oil placebo/day; Other Names: Omacor; Vitamin D3 placebo

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Collaborators: Brigham and Women's Hospital
• Investigators: Principal Investigator: Ravi I Thadhani, MD, MPH, Massachusetts General Hospital; Principal Investigator: Thomas J Wang, MD, Vanderbilt University Medical Center; Principal Investigator: Michael H Picard, MD, Massachusetts General Hospital

Publications and helpful links

General Publications

• Chandra A, Picard MH, Huang S, Gupta DK, Agusala K, Buring JE, Lee IM, Cook NR, Manson JE, Thadhani RI, Wang TJ. Impact of Vitamin D3 Versus Placebo on Cardiac Structure and Function: A Randomized Clinical Trial. J Am Heart Assoc. 2022 Nov;11(21):e025008. doi: 10.1161/JAHA.121.025008. Epub 2022 Oct 26.

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2010
• Primary Completion (Actual): April 11, 2016
• Study Completion (Actual): June 30, 2021

Study Registration Dates

• First Submitted: June 25, 2012
• First Submitted That Met QC Criteria: June 26, 2012
• First Posted (Estimate): June 28, 2012

Study Record Updates

• Last Update Posted (Actual): April 6, 2022
• Last Update Submitted That Met QC Criteria: April 5, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Keywords: Vitamin D3; Echocardiography; Left ventricular mass; Left ventricular systolic and diastolic function
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Physiological Effects of Drugs; Micronutrients; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Vitamin D; Cholecalciferol; Vitamins; Ergocalciferols
• Other Study ID Numbers: 2009P-001217

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO