VITAL Rhythm Study

NCT02178410 | Active Not Recruiting Phase 3

• 2 other identifiers: 2012P002146R01HL116690
• Study Type: interventional
• Target: 25,119
• Locations: 1 country
• Sites: 1

Brief Summary

The VITamin D and OmegA-3 TriaL (VITAL) is an ongoing randomized clinical trial of 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 individuals who do not have a prior history of these illnesses. The purpose of this ancillary study is to ascertain and adjudicate atrial fibrillation (AF) outcomes for the primary aim of testing whether omega-3 fatty acid and/or vitamin D supplementation influence atrial fibrillation risk in the general population. We also plan to examine how these agents might impact the development of AF subtypes (persistent versus paroxysmal), intermediate phenotypes for heart rhythm disorders (electrocardiographic parameters), as well as explore effects on arrhythmic death and whether baseline blood levels and/or race modify treatment effects.

Conditions

Cardiovascular Disease

Keywords

Atrial Fibrillation; Vitamin D3; Omega-3 fatty acids; Fish oil

Outcome Measures

Primary Outcomes (1)

• Atrial Fibrillation

  To assess whether omega-3 fatty acids (Omacor® 840 mg eicosapentaenoic acid (EPA) + docosahexaenoic acid (DHA) or vitamin D3 supplementation influences risk of atrial fibrillation in a general population of men and women without prior cardiovascular disease.

  7 years

Secondary Outcomes (2)

• Atrial Fibrillation

  7 years

• Arrhythmic endpoints

  5 years

Other Outcomes (1)

• Sudden Cardiac Death

  5 years

Study Arms (4)

Vitamin D + fish oil

ACTIVE COMPARATOR

Dietary Supplement: Vitamin D3; Drug: Omega-3 fatty acids (fish oil)

Vitamin D + fish oil placebo

ACTIVE COMPARATOR

Dietary Supplement: Vitamin D3; Dietary Supplement: Fish oil placebo

Vitamin D placebo + fish oil

ACTIVE COMPARATOR

Drug: Omega-3 fatty acids (fish oil); Dietary Supplement: Vitamin D3 placebo

Vitamin D placebo + fish oil placebo

PLACEBO COMPARATOR

Dietary Supplement: Fish oil placebo; Dietary Supplement: Vitamin D3 placebo

Interventions

Vitamin D3 DIETARY_SUPPLEMENT

Vitamin D3 (cholecalciferol), 2000 IU per day.

Also known as: cholecalciferol

Vitamin D + fish oil; Vitamin D + fish oil placebo

Omega-3 fatty acids (fish oil) DRUG

Omacor, 1 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 \[DHA\]).

Vitamin D + fish oil; Vitamin D placebo + fish oil

Fish oil placebo DIETARY_SUPPLEMENT

Fish oil placebo

Vitamin D + fish oil placebo; Vitamin D placebo + fish oil placebo

Vitamin D3 placebo DIETARY_SUPPLEMENT

Vitamin D3 placebo

Vitamin D placebo + fish oil; Vitamin D placebo + fish oil placebo

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \- physician diagnosis of atrial fibrillation after randomization
• and/or
• \- cardiovascular death

You may not qualify if:

• \- physician diagnosis of atrial fibrillation prior to randomization

Sponsors & Collaborators

• Brigham and Women's Hospital: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator
• Cedars-Sinai Medical Center: collaborator

Study Sites (1)

Brigham and Women's Hospital

Boston, Massachusetts, 02215, United States

Location

Related Publications (6)

• Qian F, Tintle N, Jensen PN, Lemaitre RN, Imamura F, Feldreich TR, Nomura SO, Guan W, Laguzzi F, Kim E, Virtanen JK, Steur M, Bork CS, Hirakawa Y, O'Donoghue ML, Sala-Vila A, Ardisson Korat AV, Sun Q, Rimm EB, Psaty BM, Heckbert SR, Forouhi NG, Wareham NJ, Marklund M, Riserus U, Lind L, Arnlov J, Garg P, Tsai MY, Pankow J, Misialek JR, Gigante B, Leander K, Pester JA, Albert CM, Kavousi M, Ikram A, Voortman T, Schmidt EB, Ninomiya T, Morrow DA, Bayes-Genis A, O'Keefe JH, Ong KL, Wu JHY, Mozaffarian D, Harris WS, Siscovick DS; Fatty Acids and Outcomes Research Consortium (FORCE). Omega-3 Fatty Acid Biomarkers and Incident Atrial Fibrillation. J Am Coll Cardiol. 2023 Jul 25;82(4):336-349. doi: 10.1016/j.jacc.2023.05.024.

  PMID: 37468189 RESULT

• Gencer B, Djousse L, Al-Ramady OT, Cook NR, Manson JE, Albert CM. Effect of Long-Term Marine ɷ-3 Fatty Acids Supplementation on the Risk of Atrial Fibrillation in Randomized Controlled Trials of Cardiovascular Outcomes: A Systematic Review and Meta-Analysis. Circulation. 2021 Dec 21;144(25):1981-1990. doi: 10.1161/CIRCULATIONAHA.121.055654. Epub 2021 Oct 6.

  PMID: 34612056 RESULT

• Middeldorp ME, Sandhu RK, Mao J, Gencer B, Danik JS, Moorthy V, Cook NR, Albert CM. Risk Factors for the Development of New-Onset Persistent Atrial Fibrillation: Subanalysis of the VITAL Study. Circ Arrhythm Electrophysiol. 2023 Dec;16(12):651-662. doi: 10.1161/CIRCEP.123.012334. Epub 2023 Nov 29.

  PMID: 38018439 RESULT

• Siddiqi HK, Vinayagamoorthy M, Gencer B, Ng C, Pester J, Cook NR, Lee IM, Buring J, Manson JE, Albert CM. Sex Differences in Atrial Fibrillation Risk: The VITAL Rhythm Study. JAMA Cardiol. 2022 Oct 1;7(10):1027-1035. doi: 10.1001/jamacardio.2022.2825.

  PMID: 36044209 RESULT

• Albert CM, Cook NR, Pester J, Moorthy MV, Ridge C, Danik JS, Gencer B, Siddiqi HK, Ng C, Gibson H, Mora S, Buring JE, Manson JE. Effect of Marine Omega-3 Fatty Acid and Vitamin D Supplementation on Incident Atrial Fibrillation: A Randomized Clinical Trial. JAMA. 2021 Mar 16;325(11):1061-1073. doi: 10.1001/jama.2021.1489.

  PMID: 33724323 RESULT

• Tikkanen JT, Soliman EZ, Pester J, Danik JS, Gomelskya N, Copeland T, Lee IM, Buring JE, Manson JE, Cook NR, Albert CM. A randomized clinical trial of omega-3 fatty acid and vitamin D supplementation on electrocardiographic risk profiles. Sci Rep. 2023 Jul 15;13(1):11454. doi: 10.1038/s41598-023-38344-x.

  PMID: 37454148 DERIVED

Related Links

• Welcome to the VITAL Study website

MeSH Terms

Conditions

Cardiovascular Diseases; Atrial Fibrillation

Interventions

Cholecalciferol; Fatty Acids, Omega-3; Fish Oils

Condition Hierarchy (Ancestors)

Arrhythmias, Cardiac; Heart Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Cholestenes; Cholestanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Sterols; Vitamin D; Secosteroids; Membrane Lipids; Lipids; Dietary Fats, Unsaturated; Dietary Fats; Fats; Fatty Acids, Unsaturated; Fatty Acids; Oils

Study Officials

• Christine M. Albert, M.D., M.P.H.

  Brigham and Women's Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principle Investigator

Study Record Dates

• First Submitted: June 25, 2014
• First Posted: June 30, 2014
• Study Start: October 1, 2012
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): October 1, 2026
• Last Updated: October 7, 2025

Record last verified: 2025-10

Locations

US (1)