Vitamin D and Omega-3 Trial (VITAL) (VITAL)

March 5, 2024 updated by: JoAnn E. Manson, MD, Brigham and Women's Hospital
The VITamin D and OmegA-3 TriaL (VITAL) is a randomized clinical trial in 25,871 U.S. men and women investigating whether taking daily dietary supplements of vitamin D3 (2000 IU) or omega-3 fatty acids (Omacor® fish oil, 1 gram) reduces the risk of developing cancer, heart disease, and stroke in people who do not have a prior history of these illnesses. The 5-year intervention phase (study pill-taking, median 5.3 years) has ended; post-intervention observational follow-up of study participants is ongoing.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

The VITamin D and OmegA-3 TriaL (VITAL) is a randomized clinical trial of vitamin D (in the form of vitamin D3 [cholecalciferol]) and marine omega-3 fatty acid (eicosapentaenoic acid [EPA] + docosahexaenoic acid [DHA]) supplements in the primary prevention of cancer and cardiovascular disease (CVD). Existing data from laboratory studies, epidemiologic research, small primary prevention trials, and/or large secondary prevention trials strongly suggest that these nutritional agents may reduce risk for cancer or CVD, but large primary prevention trials with adequate dosing in general populations are lacking.

VITAL tested the independent effects of vitamin D and omega-3 fatty acid supplementation on risk for developing cancer and CVD (primary, secondary, and other outcomes are specified in the Outcome Measures section). VITAL also explored (a) whether vitamin D and omega-3 fatty acid supplements exhibit synergistic or additive effects on cancer and CVD risk and (b) whether the effect of each supplement on cancer and CVD risk varies by baseline blood levels or intake of vitamin D and EPA+DHA, race/ethnicity, and body mass index (for vitamin D), as well as age, sex, sunlight exposure, calcium intake, and baseline risk factors for cancer and CVD.

Eligible participants were assigned by chance (like a coin toss) to one of four groups: (1) daily vitamin D and omega-3; (2) daily vitamin D and omega-3 placebo; (3) daily vitamin D placebo and omega-3; or (4) daily vitamin D placebo and omega-3 placebo. Participants had an equal chance of being assigned to any of these four groups and a 3 out of 4 chance of getting at least one active agent.

Participants in all groups took two pills each day -- one softgel that contained either vitamin D or vitamin D placebo and one capsule that contained either omega-3 or omega-3 placebo. Participants received their study pills in convenient calendar packages via U.S. mail.

Participants fill out a short (15-20 minute) questionnaire each year. The questionnaire asks about health; lifestyle habits such as physical exercise, diet, and smoking; use of medications and dietary supplements; family history of illness, and new medical diagnoses. We request consent for medical record review to confirm endpoints. Occasionally, participants may receive a phone call from study staff to collect information or to clarify responses on the questionnaire.

At baseline, 16,954 VITAL participants provided an optional blood sample. Approximately 6,000 of these participants provided a follow-up blood sample during years 1-5 of the trial.

At baseline, year 2, and year 4 of the trial, a subcohort of 1,054 VITAL participants living within driving distance of Boston, Massachusetts received detailed in-clinic health assessments at the Clinical and Translational Science Center (CTSC) of Brigham and Women's Hospital. During CTSC visits, participants had a clinical exam, including measurement of height, weight, other anthropometrics, blood pressure, and physical performance. They also provided fasting blood and urine samples, and underwent 2-hour oral glucose tolerance testing, lung function testing (spirometry), electrocardiograms, bone mineral density testing, 2D-echocardiography, and assessments of thinking and mood.

VITAL is supported by funding from the National Cancer Institute, National Heart, Lung and Blood Institute, Office of Dietary Supplements, National Institute of Neurological Disorders and Stroke, and the National Center for Complementary and Integrative Health. Pharmavite LLC of Northridge, California (vitamin D) and Pronova BioPharma (BASF) of Norway (Omacor® fish oil) donated the study agents, matching placebos, and packaging in the form of calendar packs.

Study Type

Interventional

Enrollment (Actual)

25871

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Brigham and Women's Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

50 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Description

To be eligible for the study, respondents had to, at study entry,:

  1. be men aged 50 or older or women aged 55 or older;
  2. have no history of cancer (except non-melanoma skin cancer), heart attack, stroke, transient ischemic attack, angina pectoris, coronary-artery bypass grafting, or percutaneous coronary intervention;
  3. have none of the following safety exclusions: history of renal failure or dialysis, hypercalcemia, hypo- or hyperparathyroidism, severe liver disease (cirrhosis), or sarcoidosis or other granulomatous diseases such as active chronic tuberculosis or granulomatosis with polyangiitis (Wegener's);
  4. have no allergy to fish or soy;
  5. have no other serious illness that would preclude participation;
  6. be consuming no more than 800 IU of vitamin D from all supplemental sources combined (individual vitamin D supplements, calcium+vitamin D supplements, medications with vitamin D [e.g., Fosamax Plus D], and multivitamins), or, if taking, willing to decrease or forego such use during the trial;
  7. be consuming no more than 1200 mg/d of calcium from all supplemental sources combined, or, if taking, willing to decrease or forego such use during the trial;
  8. not be taking fish oil supplements, or, if taking, willing to forego their use during the trial

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Vitamin D + fish oil
Dietary supplement: vitamin D3
Vitamin D3 (cholecalciferol), 2000 IU per day.
Other Names:
  • cholecalciferol
Drug: omega-3 fatty acids (fish oil)
Omacor, one 1-gram capsule per day. Each capsule of Omacor contains 840 milligrams of marine omega-3 fatty acids (465 mg of eicosapentaenoic acid [EPA] and 375 mg of docosahexaenoic acid [DHA]).
Active Comparator: Vitamin D + fish oil placebo
Dietary supplement: Fish oil placebo
Fish oil placebo
Dietary supplement: vitamin D3
Vitamin D3 (cholecalciferol), 2000 IU per day.
Other Names:
  • cholecalciferol
Active Comparator: Vitamin D placebo + fish oil
Dietary supplement: Vitamin D3 placebo
Vitamin D placebo
Drug: omega-3 fatty acids (fish oil)
Omacor, one 1-gram capsule per day. Each capsule of Omacor contains 840 milligrams of marine omega-3 fatty acids (465 mg of eicosapentaenoic acid [EPA] and 375 mg of docosahexaenoic acid [DHA]).
Placebo Comparator: Vitamin D placebo + fish oil placebo
Dietary supplement: Vitamin D3 placebo
Vitamin D placebo
Dietary supplement: Fish oil placebo
Fish oil placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With Invasive Cancer of Any Type
Time Frame: 5 years
Invasive cancer of any type
5 years
Number of Participants With a Major Cardiovascular Event
Time Frame: 5 years
Major cardiovascular event = a composite endpoint of myocardial infarction, stroke, and death from cardiovascular causes
5 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants Who Died From Invasive Cancer of Any Type
Time Frame: 5 years
Death from invasive cancer of any type
5 years
Number of Female Participants With Breast Cancer
Time Frame: 5 years
Breast cancer (in women)
5 years
Number of Male Participants With Prostate Cancer
Time Frame: 5 years
Prostate cancer (in men)
5 years
Number of Participants With Colorectal Cancer
Time Frame: 5 years
Colorectal cancer
5 years
Number of Participants With Cardiovascular Event in Expanded Composite Cardiovascular Endpoint
Time Frame: 5 years
Expanded composite cardiovascular endpoint = a composite endpoint of myocardial infarction, stroke, death from cardiovascular causes, and coronary revascularization (coronary artery bypass grafting or percutaneous coronary intervention)
5 years
Number of Participants With Myocardial Infarction
Time Frame: 5 years
Myocardial infarction
5 years
Number of Participants With Stroke
Time Frame: 5 years
Stroke
5 years
Number of Participants Who Died From Cardiovascular Causes
Time Frame: 5 years
Death from cardiovascular causes
5 years
Number of Participants Who Died From Any Cause
Time Frame: 5 years
Death from any cause
5 years
Number of Participants With Invasive Cancer of Any Type, Excluding First 2 Years of Follow-up
Time Frame: 5 years, excluding first 2 years of follow-up
Invasive cancer of any type, excluding first 2 years of follow-up
5 years, excluding first 2 years of follow-up
Number of Participants With a Major Cardiovascular Event, Excluding First 2 Years of Follow-up
Time Frame: 5 years, excluding first 2 years of follow-up
Major cardiovascular event = a composite endpoint of myocardial infarction, stroke, and death from cardiovascular causes; excluding first 2 years of follow-up
5 years, excluding first 2 years of follow-up

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants Who Died From Invasive Cancer of Any Type, Excluding First 2 Years of Follow-up
Time Frame: 5 years, excluding first 2 years of follow-up
Death from invasive cancer of any type, excluding first 2 years of follow-up
5 years, excluding first 2 years of follow-up
Number of Participants Who Died From Any Cause, Excluding First 2 Years of Follow-up
Time Frame: 5 years, excluding first 2 years of follow-up
Death from any cause, excluding first 2 years of follow-up
5 years, excluding first 2 years of follow-up
Number of Participants With Percutaneous Coronary Intervention
Time Frame: 5 years
Percutaneous coronary intervention
5 years
Number of Participants With Coronary-artery Bypass Grafting
Time Frame: 5 years
Coronary-artery bypass grafting
5 years
Number of Participants With Total Coronary Heart Disease
Time Frame: 5 years
Total coronary heart disease = a composite of myocardial infarction, coronary revascularization (percutaneous coronary intervention or coronary-artery bypass grafting), and death from coronary heart disease
5 years
Number of Participants With Ischemic Stroke
Time Frame: 5 years
Ischemic stroke
5 years
Number of Participants With Hemorrhagic Stroke
Time Frame: 5 years
Hemorrhagic stroke
5 years
Number of Participants Who Died From Myocardial Infarction
Time Frame: 5 years
Death from myocardial infarction
5 years
Number of Participants Who Died From Coronary Heart Disease
Time Frame: 5 years
Death from coronary heart disease
5 years
Number of Participants Who Died From Stroke
Time Frame: 5 years
Death from stroke
5 years
Number of Participants With Myocardial Infarction, Excluding First 2 Years of Follow-up
Time Frame: 5 years, excluding first 2 years of follow-up
Myocardial infarction, excluding first 2 years of follow-up
5 years, excluding first 2 years of follow-up
Number of Participants With Conventional Colorectal Adenoma
Time Frame: 5 years
tubular, tubulovillous, villous adenoma; adenoma w/high-grade dysplasia
5 years
Number of Participants With Serrated Colorectal Polyps
Time Frame: 5 years
hyperplastic polyp, traditional serrated adenoma, sessile serrated polyp
5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Brigham and Women's Hospital

Collaborators

National Cancer Institute (NCI)
National Heart, Lung, and Blood Institute (NHLBI)
National Institute of Neurological Disorders and Stroke (NINDS)
National Center for Complementary and Integrative Health (NCCIH)
Office of Dietary Supplements (ODS)
Pharmavite LLC
Pronova BioPharma
BASF

Investigators

  • Principal Investigator: JoAnn E. Manson, MD, DrPH, Brigham and Women's Hospital
  • Principal Investigator: Julie E. Buring, ScD, Brigham and Women's Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2010

Primary Completion (Actual)

November 10, 2018

Study Completion (Estimated)

February 1, 2025

Study Registration Dates

First Submitted

January 13, 2010

First Submitted That Met QC Criteria

July 22, 2010

First Posted (Estimated)

July 26, 2010

Study Record Updates

Last Update Posted (Actual)

March 7, 2024

Last Update Submitted That Met QC Criteria

March 5, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2009P-001217
  • U01CA138962 (U.S. NIH Grant/Contract)
  • R01CA138962 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Researchers who are interested in collaborating on research that uses VITAL data should visit the "For VITAL Investigators" section of the VITAL website, www.vitalstudy.org.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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