Vitamin D and Omega-3 Trial (VITAL)

Phase 3

Active, not recruiting

Conditions: Cancer
Cardiovascular Disease

Interventions: Dietary Supplement: Vitamin D3 placebo
Dietary Supplement: vitamin D3
Drug: omega-3 fatty acids (fish oil)
Dietary Supplement: Fish oil placebo

Registration Number: NCT01169259

Lead Sponsor: Brigham and Women's Hospital

Brief Summary: 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.

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.

Recruitment & Eligibility

Status: ACTIVE_NOT_RECRUITING

Sex: All

Target Recruitment: 25871

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: FACTORIAL

Arm && Interventions

Group	Intervention	Description
Vitamin D + fish oil	omega-3 fatty acids (fish oil)	-
Vitamin D placebo + fish oil	omega-3 fatty acids (fish oil)	-
Vitamin D placebo + fish oil placebo	Fish oil placebo	-
Vitamin D placebo + fish oil placebo	Vitamin D3 placebo	-
Vitamin D + fish oil	vitamin D3	-
Vitamin D + fish oil placebo	Fish oil placebo	-
Vitamin D placebo + fish oil	Vitamin D3 placebo	-
Vitamin D + fish oil placebo	vitamin D3	-

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Stroke	5 years	Stroke
Number of Female Participants With Breast Cancer	5 years	Breast cancer (in women)
Number of Participants Who Died From Invasive Cancer of Any Type	5 years	Death from invasive cancer of any type
Number of Participants Who Died From Cardiovascular Causes	5 years	Death from cardiovascular causes
Number of Male Participants With Prostate Cancer	5 years	Prostate cancer (in men)
Number of Participants With Cardiovascular Event in Expanded Composite Cardiovascular Endpoint	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)
Number of Participants With Myocardial Infarction	5 years	Myocardial infarction
Number of Participants With Colorectal Cancer	5 years	Colorectal cancer
Number of Participants With Invasive Cancer of Any Type, Excluding First 2 Years of Follow-up	5 years, excluding first 2 years of follow-up	Invasive cancer of any type, excluding first 2 years of follow-up
Number of Participants Who Died From Any Cause	5 years	Death from any cause
Number of Participants With a Major Cardiovascular Event, Excluding First 2 Years of Follow-up	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