Vitamin D and Omega-3 Trial (VITAL)

Cancer Clinical Trial

— VITAL  

Official title:

Vitamin D and Omega-3 Trial (VITAL)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01169259
• Other study ID #: 2009P-001217
• Secondary ID: U01CA138962R01CA
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: July 2010
• Est. completion date: February 2025

Study information

• Verified date: March 2024
• Source: Brigham and Women's Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Active, not recruiting
• Enrollment: 25871
• Est. completion date: February 2025
• Est. primary completion date: November 10, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 50 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Cancer
• Cardiovascular Disease
• Cardiovascular Diseases

Intervention

Dietary Supplement:
• vitamin D3
Vitamin D3 (cholecalciferol), 2000 IU per day.

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]).

Dietary Supplement:
• Vitamin D3 placebo
Vitamin D placebo
• Fish oil placebo
Fish oil placebo

Locations

Country	Name	City	State
United States	Brigham and Women's Hospital	Boston	Massachusetts

Sponsors (9)

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

Country where clinical trial is conducted

United States, 

References & Publications (7)

Bassuk SS, Manson JE, Lee IM, Cook NR, Christen WG, Bubes VY, Gordon DS, Copeland T, Friedenberg G, D'Agostino DM, Ridge CY, MacFadyen JG, Kalan K, Buring JE. Baseline characteristics of participants in the VITamin D and OmegA-3 TriaL (VITAL). Contemp Clin Trials. 2016 Mar;47:235-43. doi: 10.1016/j.cct.2015.12.022. Epub 2016 Jan 6. — View Citation

Manson JE, Bassuk SS, Lee IM, Cook NR, Albert MA, Gordon D, Zaharris E, Macfadyen JG, Danielson E, Lin J, Zhang SM, Buring JE. The VITamin D and OmegA-3 TriaL (VITAL): rationale and design of a large randomized controlled trial of vitamin D and marine omega-3 fatty acid supplements for the primary prevention of cancer and cardiovascular disease. Contemp Clin Trials. 2012 Jan;33(1):159-71. doi: 10.1016/j.cct.2011.09.009. Epub 2011 Oct 2. — View Citation

Manson JE, Cook NR, Lee IM, Christen W, Bassuk SS, Mora S, Gibson H, Albert CM, Gordon D, Copeland T, D'Agostino D, Friedenberg G, Ridge C, Bubes V, Giovannucci EL, Willett WC, Buring JE; VITAL Research Group. Marine n-3 Fatty Acids and Prevention of Cardiovascular Disease and Cancer. N Engl J Med. 2019 Jan 3;380(1):23-32. doi: 10.1056/NEJMoa1811403. Epub 2018 Nov 10. — View Citation

Manson JE, Cook NR, Lee IM, Christen W, Bassuk SS, Mora S, Gibson H, Gordon D, Copeland T, D'Agostino D, Friedenberg G, Ridge C, Bubes V, Giovannucci EL, Willett WC, Buring JE; VITAL Research Group. Vitamin D Supplements and Prevention of Cancer and Cardiovascular Disease. N Engl J Med. 2019 Jan 3;380(1):33-44. doi: 10.1056/NEJMoa1809944. Epub 2018 Nov 10. — View Citation

Pradhan AD, Manson JE. Update on the Vitamin D and OmegA-3 trial (VITAL). J Steroid Biochem Mol Biol. 2016 Jan;155(Pt B):252-6. doi: 10.1016/j.jsbmb.2015.04.006. Epub 2015 Apr 9. — View Citation

Song M, Lee IM, Manson JE, Buring JE, Dushkes R, Gordon D, Walter J, Wu K, Chan AT, Ogino S, Fuchs CS, Meyerhardt JA, Giovannucci EL. No Association Between Vitamin D Supplementation and Risk of Colorectal Adenomas or Serrated Polyps in a Randomized Trial. Clin Gastroenterol Hepatol. 2021 Jan;19(1):128-135.e6. doi: 10.1016/j.cgh.2020.02.013. Epub 2020 Feb 13. — View Citation

Song M, Lee IM, Manson JE, Buring JE, Dushkes R, Gordon D, Walter J, Wu K, Chan AT, Ogino S, Fuchs CS, Meyerhardt JA, Giovannucci EL; VITAL Research Group. Effect of Supplementation With Marine omega-3 Fatty Acid on Risk of Colorectal Adenomas and Serrated Polyps in the US General Population: A Prespecified Ancillary Study of a Randomized Clinical Trial. JAMA Oncol. 2020 Jan 1;6(1):108-115. doi: 10.1001/jamaoncol.2019.4587. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Number of Participants Who Died From Invasive Cancer of Any Type, 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
Other	Number of Participants Who Died From Any Cause, 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
Other	Number of Participants With Percutaneous Coronary Intervention	Percutaneous coronary intervention	5 years
Other	Number of Participants With Coronary-artery Bypass Grafting	Coronary-artery bypass grafting	5 years
Other	Number of Participants With Total Coronary Heart Disease	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
Other	Number of Participants With Ischemic Stroke	Ischemic stroke	5 years
Other	Number of Participants With Hemorrhagic Stroke	Hemorrhagic stroke	5 years
Other	Number of Participants Who Died From Myocardial Infarction	Death from myocardial infarction	5 years
Other	Number of Participants Who Died From Coronary Heart Disease	Death from coronary heart disease	5 years
Other	Number of Participants Who Died From Stroke	Death from stroke	5 years
Other	Number of Participants With Myocardial Infarction, 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
Other	Number of Participants With Conventional Colorectal Adenoma	tubular, tubulovillous, villous adenoma; adenoma w/high-grade dysplasia	5 years
Other	Number of Participants With Serrated Colorectal Polyps	hyperplastic polyp, traditional serrated adenoma, sessile serrated polyp	5 years
Primary	Number of Participants With Invasive Cancer of Any Type	Invasive cancer of any type	5 years
Primary	Number of Participants With a Major Cardiovascular Event	Major cardiovascular event = a composite endpoint of myocardial infarction, stroke, and death from cardiovascular causes	5 years
Secondary	Number of Participants Who Died From Invasive Cancer of Any Type	Death from invasive cancer of any type	5 years
Secondary	Number of Female Participants With Breast Cancer	Breast cancer (in women)	5 years
Secondary	Number of Male Participants With Prostate Cancer	Prostate cancer (in men)	5 years
Secondary	Number of Participants With Colorectal Cancer	Colorectal cancer	5 years
Secondary	Number of Participants With Cardiovascular Event in Expanded Composite Cardiovascular Endpoint	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
Secondary	Number of Participants With Myocardial Infarction	Myocardial infarction	5 years
Secondary	Number of Participants With Stroke	Stroke	5 years
Secondary	Number of Participants Who Died From Cardiovascular Causes	Death from cardiovascular causes	5 years
Secondary	Number of Participants Who Died From Any Cause	Death from any cause	5 years
Secondary	Number of Participants With Invasive Cancer of Any Type, 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
Secondary	Number of Participants With a Major Cardiovascular Event, 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

External Links

•   VITAL study website