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COcoa Supplement and Multivitamin Outcomes Study (COSMOS)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02422745
Recruitment Status : Active, not recruiting
First Posted : April 21, 2015
Last Update Posted : December 10, 2019
Sponsor:
Collaborators:
Fred Hutchinson Cancer Research Center
Mars, Inc.
Pfizer
Columbia University
Information provided by (Responsible Party):
JoAnn E. Manson, MD, Brigham and Women's Hospital

Tracking Information
First Submitted Date  ICMJE April 17, 2015
First Posted Date  ICMJE April 21, 2015
Last Update Posted Date December 10, 2019
Study Start Date  ICMJE June 2015
Estimated Primary Completion Date November 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 11, 2018)
  • Cardiovascular disease (CVD) events [ Time Frame: 5 years ]
    CVD events include myocardial infarction, stroke, coronary revascularization procedures, and cardiovascular deaths. CVD events are confirmed by review of discharge summaries, ECG's, laboratory reports, test reports, and death certificates.
  • Invasive cancer [ Time Frame: 5 years ]
    Diagnoses of invasive cancer are confirmed by review of discharge summaries, pathology reports, operative reports, and diagnostic or treatment procedure reports, including both inpatient and outpatient procedures.
Original Primary Outcome Measures  ICMJE
 (submitted: April 17, 2015)
  • cardiovascular disease [ Time Frame: 5 years ]
  • cancer [ Time Frame: 5 years ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 11, 2018)
  • Combined endpoint of major cardiovascular events plus all-cause mortality [ Time Frame: 5 years ]
  • Myocardial infarction [ Time Frame: 5 years ]
  • Stroke [ Time Frame: 5 years ]
  • Cardiovascular mortality [ Time Frame: 5 years ]
  • Coronary revascularization [ Time Frame: 5 years ]
  • Total mortality [ Time Frame: 5 years ]
  • Breast cancer [ Time Frame: 5 years ]
  • Colorectal cancer [ Time Frame: 5 years ]
  • Lung cancer [ Time Frame: 5 years ]
  • Blood flavonoid levels [ Time Frame: 2 years ]
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures
 (submitted: May 11, 2018)
  • Cognitive function [ Time Frame: 2-5 years ]
    Internet-based neuropsychological testing battery, including tests of novel object recognition, spatial learning, attention, inhibition, and executive control; face-to-face and computerized assessments of verbal memory, psychomotor speed, and executive function, working memory and organization; concentration and processing speed; visual recall; oral reading; receptive vocabulary; cognitive flexibility; attention; inhibitory control
  • Systolic and diastolic blood pressure [ Time Frame: 2 years ]
  • Pulse wave velocity and central blood pressure indices [ Time Frame: 2 years ]
    Assessed by pulse wave analysis
  • Physical performance [ Time Frame: 2 years ]
    Balance tests, grip strength, timed chair stands, walking speed
  • Bone mass density in hip, spine, and total body, and body composition [ Time Frame: 2 years ]
    Assessed by dual x-ray absorptiometry
  • Body composition [ Time Frame: 2 years ]
  • Metabolic and functional change within hippocampus [ Time Frame: 2 years ]
    Assessed with CBV MRI
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE COcoa Supplement and Multivitamin Outcomes Study
Official Title  ICMJE COcoa Supplement and Multivitamin Outcomes Study
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, and cardiovascular mortality) and cancer.
Detailed Description

The COcoa Supplement and Multivitamin Outcomes Study (COSMOS) is a randomized clinical trial of cocoa extract supplement (containing a total of 600 mg/d flavanols, including 80 mg. (-)-epicatechins), and a standard multivitamin supplement to reduce the risk of cardiovascular disease and cancer among women aged 65 years and older and men aged 60 years and older.

Participants in COSMOS were recruited from among Women's Health Initiative (WHI) Extension Study cohort members; non-randomized respondents to mailings for the VITamin D and OmegA-3 TriaL (VITAL); respondents to nationwide invitational mailings to age-eligible adults; and volunteers who learned about the trial through the media or through ResearchMatch.org, an electronic recruitment website.

Several small randomized trials have demonstrated benefits for cocoa flavanols on intermediate outcomes, including blood pressure, lipids, insulin sensitivity, and flow-mediated vasodilation. For multivitamins, a prior large-scale randomized trial in middle-aged and older men showed a significant reduction in cancer, but comparable trial data in women are lacking. For both interventions, a large-scale clinical trial such as COSMOS could have major clinical and public health implications.

Eligible participants have been assigned by chance (like a coin toss) to one of four groups: (1) daily cocoa extract and multivitamin; (2) daily cocoa extract and multivitamin placebo; (3) daily cocoa extract placebo and multivitamin; or (4) daily cocoa extract placebo and multivitamin placebo. Participants have an equal chance of being assigned to any of these four groups and a 3 out of 4 chance of receiving at least one active agent.

Participants in all groups take three pills each day: two capsules that contain either cocoa extract or cocoa extract placebo, and one tablet that contains either multivitamin or multivitamin placebo. Participants receive their study pills in convenient calendar packs via U.S. mail.

Participants are asked to complete mailed questionnaires each year. The questionnaires ask about health; lifestyle habits, such as diet, physical activity, and smoking; use of medications and dietary supplements; family history of illness and new medical diagnoses. Occasionally, participants may receive a phone call from study staff to collect information or clarify responses on the questionnaires.

At baseline, approximately 7,000 COSMOS participants provided optional blood and urine samples, which will be used to determine whether the study agents significantly change biomarkers and other risk factors related to cardiovascular disease and cancer. Selected participants either have specimens collected through mailed specimen collection kits that are returned by the participant, or have blood, urine, blood pressure, and anthropometric measurements collected by technicians from Examination Management Services, Inc. (EMSI), a national clinical services provider. A subgroup of those who provide baseline specimens and measurements are asked to provide follow-up samples and measurements.

At baseline and after each year of follow-up, approximately 4,000 COSMOS participants complete web-based assessments of cognitive function. During the trial, participants will complete up to 4 assessments, each of which takes approximately 25 minutes to complete. The trial will assess whether the study agents significantly affect change in cognitive function over time.

At baseline and year 2 of the trial, approximately 600 participants living within driving distance of Boston, Massachusetts provide additional measurements from in-clinic study visits at the Clinical and Translational Science Center (CTSC) of Brigham and Women's Hospital. These visits include cognitive function assessments, anthropometrics, physical function assessments, blood pressure and other measurements. The trial will assess whether the study agents significantly affect changes in these variables over time.

Primary Hypotheses:

  1. A cocoa extract supplement will reduce the risk of major cardiovascular events, defined as a composite endpoint of myocardial infarction, stroke, cardiovascular mortality, and coronary revascularization;
  2. A daily multivitamin will reduce the risk of invasive cancer (excluding non-melanoma skin cancer).

Secondary Hypotheses:

  1. Cocoa extract will reduce the risk of invasive cancer (excluding non-melanoma skin cancer);
  2. A daily multivitamin will reduce the risk of major cardiovascular events;
  3. Cocoa extract and/or a daily multivitamin will reduce the combined endpoint of major cardiovascular events plus all-cause mortality;
  4. Cocoa extract and/or a daily multivitamin will reduce the risk of individual cardiovascular events, including myocardial infarction, stroke, cardiovascular mortality, coronary revascularization, and total mortality; plus site-specific cancers, including breast, colorectal, and lung cancer;
  5. A daily multivitamin will reduce the risk of cancer among women and men with a history of cancer at baseline;
  6. In a subset of equal numbers of female and male COSMOS respondents who provide baseline bloods, cocoa extract and/or a daily multivitamin will significantly change levels of blood flavonoids from baseline to 2 years of follow-up.

Tertiary Aim:

To assess whether the cocoa extract and/or a daily multivitamin exhibit synergistic effects on risk of major cardiovascular events or cancer, and if the effects vary by nutritional status or medication use.

Aims of Clinical and Translational Science Center (CTSC) Component:

To test whether the cocoa extract and/or a daily multivitamin has beneficial effects on:

  1. Systolic and diastolic blood pressure;
  2. Pulse wave velocity (PWV) and central blood pressure indices as measured by pulse wave analysis;
  3. Cognitive function and memory;
  4. Physical performance as assessed by balance tests, grip strength, timed chair stands, and walking speed,
  5. Bone loss in the spine, hip and total body as assessed by bone-mineral density (BMD) and changes in body composition as assessed by dual x-ray absorpiometry (DXA);
  6. Metabolic and functional changes within the hippocampus using cerebral blood volume (CBV) MRI.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Prevention
Condition  ICMJE
  • Cardiovascular Disease
  • Cancer
Intervention  ICMJE
  • Dietary Supplement: Cocoa extract
    2 capsules each day containing a total of 600 mg cocoa flavanols, including 80 mg (-)-epicatechin, and 50 mg theobromine
  • Dietary Supplement: Multivitamin
    Multivitamin
  • Dietary Supplement: Cocoa extract placebo
    Cocoa extract placebo
  • Dietary Supplement: Multivitamin placebo
    Multivitamin placebo
Study Arms  ICMJE
  • Active Comparator: Cocoa extract + multivitamin
    Interventions:
    • Dietary Supplement: Cocoa extract
    • Dietary Supplement: Multivitamin
  • Active Comparator: Cocoa extract + multivitamin placebo
    Interventions:
    • Dietary Supplement: Cocoa extract
    • Dietary Supplement: Multivitamin placebo
  • Active Comparator: Cocoa extract placebo + multivitamin
    Interventions:
    • Dietary Supplement: Multivitamin
    • Dietary Supplement: Cocoa extract placebo
  • Placebo Comparator: Cocoa extract placebo + multivitamin placebo
    Interventions:
    • Dietary Supplement: Cocoa extract placebo
    • Dietary Supplement: Multivitamin placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: May 11, 2018)
21445
Original Estimated Enrollment  ICMJE
 (submitted: April 17, 2015)
18000
Estimated Study Completion Date  ICMJE November 2021
Estimated Primary Completion Date November 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Women ≥ 65 years of age participating in the Women's Health Initiative (WHI) Extension Study.
  2. Men ≥ 60 years of age and women age ≥ 65 years of age who were contacted for but not randomized into the VITAL trial.
  3. 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.
  4. Willing to participate, as evidenced by providing informed consent and completing all required baseline forms.

Exclusion Criteria:

  1. History of myocardial infarction or stroke.
  2. Diagnosed with invasive cancer other than non-melanoma skin cancer in the last 2 years prior to enrollment.
  3. Any serious illness that would preclude participation and/or completion of the trial, including the diagnosis of kidney failure and current dialysis treatment.
  4. Taking cocoa extract or multivitamin supplements and not willing to forego use during the trial.
  5. Taking total supplemental vitamin D > 1,000 IU/day and not willing to forego use during the trial.
  6. Taking total supplemental calcium > 1,200 mg/day and not willing to forego use during the trial.
  7. Extreme sensitivity to caffeine.
  8. Consume < 75% of the expected number of both types of supplements during the run-in phase.
  9. Unable to communicate in English due to language barrier or mental incapacity.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 60 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02422745
Other Study ID Numbers  ICMJE 2014D001652
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party JoAnn E. Manson, MD, Brigham and Women's Hospital
Study Sponsor  ICMJE Brigham and Women's Hospital
Collaborators  ICMJE
  • Fred Hutchinson Cancer Research Center
  • Mars, Inc.
  • Pfizer
  • Columbia University
Investigators  ICMJE
Principal Investigator: JoAnn E. Manson, MD Brigham and Women's Hospital
PRS Account Brigham and Women's Hospital
Verification Date December 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP