COcoa Supplement and Multivitamin Outcomes Study

NCT02422745 | Completed Phase 4 Results DMC

• 1 other identifier: 2014P002768
• Study Type: interventional
• Target: 21,442
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this study is to determine whether taking daily, dietary supplements of cocoa extract (containing cocoa flavanols and theobromine from the cocoa bean) and/or a standard multivitamin reduces the risk of developing cardiovascular disease (including heart attack, stroke, coronary revascularization, unstable angina or acute coronary syndrome (ACS) requiring hospitalization, carotid artery surgery, and peripheral artery surgery or angioplasty, and cardiovascular mortality) and cancer.

Conditions

Cardiovascular Disease; Cancer

Keywords

Cocoa extract multivitamins cardiovascular disease cancer

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Total Cardiovascular Disease (CVD) Events

  CVD events include myocardial infarction, stroke, cardiovascular deaths, coronary revascularization procedures, unstable angina or acute coronary syndrome (ACS) requiring hospitalization, carotid artery surgery, and peripheral artery surgery or angioplasty. CVD events are confirmed by review of discharge summaries, ECG's, laboratory reports, test reports, radiology reports, surgical reports, medical records for reports of increased pain, use of medication to alleviate pain, and evidence of troponin leak, and death certificates.

  4 years

• Number of Participants With Invasive Cancer Events

  Diagnoses of invasive cancer are confirmed by review of discharge summaries, pathology reports, operative reports, surgical reports, and diagnostic or treatment procedure reports, including both inpatient and outpatient procedures.

  4 years

Secondary Outcomes (14)

• Number of Participants With Composite Endpoint of MI, Stroke, Cardiovascular Mortality, and Coronary Revascularization

  4 years

• Number of Participants With Total Cardiovascular Events Plus All-Cause Mortality

  4 years

• Number of Participants With Myocardial Infarction

  4 years

• Number of Participants With Stroke

  4 years

• Number of Participants With Cardiovascular Mortality

  4 years

Other Outcomes (5)

• Systolic and Diastolic Blood Pressure

  2 years

• Pulse Wave Velocity and Central Blood Pressure Indices

  2 years

• Physical Performance

  2 years

Study Arms (4)

Cocoa extract + multivitamin

ACTIVE COMPARATOR

Dietary Supplement: Cocoa extract; Dietary Supplement: Multivitamin

Cocoa extract + multivitamin placebo

ACTIVE COMPARATOR

Dietary Supplement: Cocoa extract; Dietary Supplement: Multivitamin placebo

Cocoa extract placebo + multivitamin

ACTIVE COMPARATOR

Dietary Supplement: Multivitamin; Dietary Supplement: Cocoa extract placebo

Cocoa extract placebo + multivitamin placebo

PLACEBO COMPARATOR

Dietary Supplement: Cocoa extract placebo; Dietary Supplement: Multivitamin placebo

Interventions

Cocoa extract DIETARY_SUPPLEMENT

2 capsules each day containing a total of 500 mg cocoa flavanols, including 80 mg (-)-epicatechin, and 50 mg theobromine

Cocoa extract + multivitamin; Cocoa extract + multivitamin placebo

Multivitamin DIETARY_SUPPLEMENT

Multivitamin

Cocoa extract + multivitamin; Cocoa extract placebo + multivitamin

Cocoa extract placebo DIETARY_SUPPLEMENT

Cocoa extract placebo

Cocoa extract placebo + multivitamin; Cocoa extract placebo + multivitamin placebo

Multivitamin placebo DIETARY_SUPPLEMENT

Multivitamin placebo

Cocoa extract + multivitamin placebo; Cocoa extract placebo + multivitamin placebo

Eligibility Criteria

• Age: 60 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Women ≥ 65 years of age participating in the Women's Health Initiative (WHI) Extension Study.
• Men ≥ 60 years of age and women age ≥ 65 years of age who were contacted for but not randomized into the VITAL trial.
• Other women ≥ 65 years of age and men aged ≥ 60 years of age who responded to targeted mass mailings and volunteers who learned about the trial through the media or through ResearchMatch.org, an electronic recruitment website.
• Willing to participate, as evidenced by providing informed consent and completing all required baseline forms.

You may not qualify if:

• History of myocardial infarction or stroke.
• Diagnosed with invasive cancer other than non-melanoma skin cancer in the last 2 years prior to enrollment.
• Any serious illness that would preclude participation and/or completion of the trial, including the diagnosis of kidney failure and current dialysis treatment.
• Taking cocoa extract or multivitamin supplements and not willing to forego use during the trial.
• Taking total supplemental vitamin D \> 1,000 IU/day and not willing to forego use during the trial.
• Taking total supplemental calcium \> 1,200 mg/day and not willing to forego use during the trial.
• Extreme sensitivity to caffeine.
• Consume \< 75% of the expected number of both types of supplements during the run-in phase.
• Unable to communicate in English due to language barrier or mental incapacity.

Sponsors & Collaborators

• Brigham and Women's Hospital: lead
• Fred Hutchinson Cancer Center: collaborator
• Mars, Inc.: collaborator
• Pfizer: collaborator

Study Sites (2)

Brigham and Women's Hospital

Boston, Massachusetts, 02215, United States

Location

Fred Hutchinson Cancer Research Center

Seattle, Washington, 98109, United States

Location

Related Publications (7)

• Hamaya R, Li S, Lau J, Rautiainen S, Haring B, Liu S, Shadyab AH, Martin LW, Wassertheil-Smoller S, Rist PM, Manson JE, Sesso HD; COSMOS Research Group. Long-term effect of multivitamin supplementation on incident self-reported hypertension and blood pressure changes in the COSMOS trial. Am J Hypertens. 2025 Nov 20:hpaf224. doi: 10.1093/ajh/hpaf224. Online ahead of print.

  PMID: 41264477 DERIVED

• Vyas CM, Manson JE, Sesso HD, Cook NR, Rist PM, Weinberg A, Moorthy MV, Baker LD, Espeland MA, Yeung LK, Brickman AM, Okereke OI. Effect of multivitamin-mineral supplementation versus placebo on cognitive function: results from the clinic subcohort of the COcoa Supplement and Multivitamin Outcomes Study (COSMOS) randomized clinical trial and meta-analysis of 3 cognitive studies within COSMOS. Am J Clin Nutr. 2024 Mar;119(3):692-701. doi: 10.1016/j.ajcnut.2023.12.011. Epub 2024 Jan 18.

  PMID: 38244989 DERIVED

• Vyas CM, Manson JE, Sesso HD, Rist PM, Weinberg A, Kim E, Moorthy MV, Cook NR, Okereke OI. Effect of cocoa extract supplementation on cognitive function: results from the clinic subcohort of the COSMOS trial. Am J Clin Nutr. 2024 Jan;119(1):39-48. doi: 10.1016/j.ajcnut.2023.10.031. Epub 2023 Dec 7.

  PMID: 38070683 DERIVED

• Sesso HD, Rist PM, Aragaki AK, Rautiainen S, Johnson LG, Friedenberg G, Copeland T, Clar A, Mora S, Moorthy MV, Sarkissian A, Wactawski-Wende J, Tinker LF, Carrick WR, Anderson GL, Manson JE; COSMOS Research Group. Multivitamins in the prevention of cancer and cardiovascular disease: the COcoa Supplement and Multivitamin Outcomes Study (COSMOS) randomized clinical trial. Am J Clin Nutr. 2022 Jun 7;115(6):1501-1510. doi: 10.1093/ajcn/nqac056.

  PMID: 35294969 DERIVED

• Sesso HD, Manson JE, Aragaki AK, Rist PM, Johnson LG, Friedenberg G, Copeland T, Clar A, Mora S, Moorthy MV, Sarkissian A, Carrick WR, Anderson GL; COSMOS Research Group. Effect of cocoa flavanol supplementation for the prevention of cardiovascular disease events: the COcoa Supplement and Multivitamin Outcomes Study (COSMOS) randomized clinical trial. Am J Clin Nutr. 2022 Jun 7;115(6):1490-1500. doi: 10.1093/ajcn/nqac055.

  PMID: 35294962 DERIVED

• Rist PM, Sesso HD, Johnson LG, Aragaki AK, Wang L, Rautiainen S, Hazra A, Tobias DK, LeBoff MS, Schroeter H, Friedenberg G, Copeland T, Clar A, Tinker LF, Hunt RP, Bassuk SS, Sarkissian A, Smith DC, Pereira E, Carrick WR, Wion ES, Schoenberg J, Anderson GL, Manson JE; COSMOS Research Group. Design and baseline characteristics of participants in the COcoa Supplement and Multivitamin Outcomes Study (COSMOS). Contemp Clin Trials. 2022 May;116:106728. doi: 10.1016/j.cct.2022.106728. Epub 2022 Mar 12.

  PMID: 35288332 DERIVED

• Baker LD, Rapp SR, Shumaker SA, Manson JE, Sesso HD, Gaussoin SA, Harris D, Caudle B, Pleasants D, Espeland MA; COSMOS-Mind Research Group. Design and baseline characteristics of the cocoa supplement and multivitamin outcomes study for the Mind: COSMOS-Mind. Contemp Clin Trials. 2019 Aug;83:57-63. doi: 10.1016/j.cct.2019.06.019. Epub 2019 Jul 2.

  PMID: 31271875 DERIVED

Related Links

• COSMOS Trial website

MeSH Terms

Conditions

Cardiovascular Diseases; Neoplasms

Interventions

Chocolate; Geritol

Intervention Hierarchy (Ancestors)

Food; Diet, Food, and Nutrition; Physiological Phenomena; Food and Beverages

Results Point of Contact

• Title: COSMOS Study Director
• Organization: Brigham and Women's Hospital; 900 Commonwealth Ave, 3rd fl.; Boston, MA 02215

cosmostrial@partners.org

1-800-633-6913

Study Officials

• JoAnn E. Manson, MD

  Brigham and Women's Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: April 17, 2015
• First Posted: April 21, 2015
• Study Start: June 1, 2015
• Primary Completion: July 1, 2022
• Study Completion: June 5, 2023
• Last Updated: September 24, 2025
• Results First Posted: September 19, 2024

Record last verified: 2025-09

Locations

US (2)