COcoa Supplement and Multivitamin Outcomes Study for the Mind (COSMOS-Mind)

August 18, 2023 updated by: Wake Forest University Health Sciences

COcoa Supplement and Multivitamin Outcomes Study-Mind

The parent trial (COcoa Supplement and Multivitamin Outcomes Study, COSMOS; NCT02422745) is a randomized clinical trial of cocoa extract supplement (containing a total of 500 mg/d flavanols, including 80 mg. (-)-epicatechins), and a standard multivitamin supplement to reduce the risk of cardiovascular disease and cancer among men aged 60 years and older and women aged 65 years and older. A cognitive ancillary study (COSMOS-Mind) is being conducted among men and women, 65 years and older, who are enrolled in COSMOS and will examine whether the cocoa extract supplement or the multivitamin supplement improves cognitive function and reduces risk of cognitive impairment, including Alzheimer's disease (AD) and other related types of dementia. Participants at the Wake Forest site will only be getting a phone call.

Study Overview

Status

Completed

Conditions

Detailed Description

Identifying a safe, affordable, and well-tolerated intervention that prevents cognitive decline in older adults is of critical public health importance. There is compelling evidence from basic science, and small clinical studies that cocoa flavanols may protect cognitive function in older adults and reduce risk of Alzheimer's disease (AD) and related dementia. Thus, this intervention could have important downstream benefits for health care utilization and cost, caregiver burden, and overall quality of life for older adults. Cocoa flavanol effects on cognition, however, need to be assessed in a definitive clinical trial.

The parent trial (COSMOS) will enroll 21,442 women and men nationwide, drawn from the Women's Health Initiative (WHI) participant cohort and the VITamin D and OmegA-3 TriaL (VITAL) non-randomized respondent cohort, and will be conducted primarily by mail to assess whether high-potency cocoa flavanol extract and a multivitamin - alone or in combination - will reduce risk of cardiovascular disease and cancer over 3 years of follow-up.

After the COSMOS trial began, an advanced method to analyze cocoa flavanols was accredited by Association of Official Agricultural Chemists (AOAC) International as a First Action Official Method of Analysis https://doi.org/10.1093/jaoacint/qsaa132 [secure-web.cisco.com]). This updated method relies on a reference material (RM8403) recently standardized and made commercially available by the U.S. National Institute of Standards and Technology. While the actual cocoa flavanol content of the COSMOS intervention remained unchanged throughout the trial, the application of this new analytical method led to expected changes in how the total cocoa flavanol content is now reported. Applying AOAC 2020.05/RM8403 to the COSMOS intervention, the total cocoa flavanol content of the COSMOS intervention is now 500 mg/day. Reporting of (-)-epicatechin content remained unaffected. Going forward, this record will therefore apply AOAC 2020.05/RM8403 and report that the COSMOS intervention tested 500 mg/day of cocoa flavanols, including 80 mg of (-)-epicatechin.

Once participants are enrolled in COSMOS, the study team at Brigham and Women's Hospital will provide contact information and other parent trial outcomes for COSMOS-Mind participants to the Wake Forest team using a secure web-based data transfer system. This seamless exchange of information between sites will permit timely accounting to ensure that the targeted demographics for enrollment are achieved (e.g. gender, age, race, ethnicity).

COSMOS-Mind will only be administered a telephone cognitive assessment to all participants at enrollment (baseline), and annually for 3 years of follow-up by trained and certified staff of the Wake Forest COSMOS-Mind team.

Study Type

Observational

Enrollment (Actual)

2262

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • North Carolina
      • Winston-Salem, North Carolina, United States, 27157
        • Wake Forest School of Medicine

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

65 years and older (Older Adult)

Accepts Healthy Volunteers

Yes

Sampling Method

Non-Probability Sample

Study Population

COSMOS-Mind will include 2,000 participants from the COSMOS parent trial who are at least 65 years of age, with approximately equal distribution of women and men.

Description

Participants in COSMOS (NCT02422745) who meet the following criteria are eligible to participate in this ancillary study:

Inclusion Criteria -

  1. Men and women 65 years and older.
  2. Willingness to participate.
  3. Ability to answer questions by phone.

Exclusion Criteria -

  1. Participants who are co-enrolled in the WHI Memory Study.
  2. Participants with insulin-dependent diabetes.
  3. Participants who are unable to complete the baseline cognitive assessments.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Cocoa extract + multivitamin placebo
2 capsules containing 500 mg/d cocoa extract; daily MTV placebo
Cocoa extract placebo + multivitamin
Cocoa extract placebo (2 capsules/d); daily MTV
Cocoa extract placebo + multivitamin placebo
Cocoa extract placebo (2 capsules/d); daily MTV placebo
Cocoa extract + multivitamin (MTV)
2 capsules containing 500 mg/d cocoa extract; daily MTV

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Global Cognitive Function: Average Change Over Follow-up From Baseline
Time Frame: From Baseline through Year 3
A composite cognitive measure that averages individual test z-scores of the Telephone Interview for Cognitive Status-modified (TICSm) Total and Long, the Immediate and Delayed Story Recall tests, the Oral Trail Making A and B tests (log-transformed), the Category Fluency and Verbal Fluency tests, and the Number Span Backward and Forward tests. Scores are ordered so that better performance corresponds to higher positive scores. Longitudinal data are used to create a linear contrast for the primary analysis to compare the difference between the average of scores at Years 1, 2, and 3 and the baseline score, i.e. (z1+z2+z3)/3 - z0, where z's denote the composited measures at baseline and years 1-3. This contrast is fitted using a random effects model for repeated measures. The primary comparison is for the margins of the factorial design: active cocoa flavonal (with or without active multivitamin) versus placebo flavonal (with or without active multivitamin).
From Baseline through Year 3

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Composite Cognitive Function
Time Frame: From baseline through year 3
A composite cognitive measure that averages individual test z-scores of the Telephone Interview for Cognitive Status-modified (TICSm) Total and Long, the Immediate and Delayed Story Recall tests, the Oral Trail Making A and B tests (log-transformed), the Category Fluency and Verbal Fluency tests, and the Number Span Backward and Forward tests. Scores are ordered so that better performance corresponds to higher positive scores. Longitudinal data are used to create a linear contrast for the primary analysis to compare the difference between the average of scores at Years 1, 2, and 3 and the baseline score, i.e. (z1+z2+z3)/3 - z0, where z's denote the composited measures at baseline and years 1-3. This contrast is fitted using a random effects model for repeated measures. The comparison for this secondary outcome is based on the margins of the factorial design to compare multivitamin (with or without cocoa flavonal) with multivitamin placebo (with or without cocoa flavonal)
From baseline through year 3
Incident Mild Cognitive Impairment
Time Frame: From baseline through year 3
Mild cognitive impairment based on centralized adjudication of cognitive test scores and input from a proxy. Limited to participants free of mild cognitive impairment at baseline. Incidence over 3 years of follow-up.
From baseline through year 3
Incidence of Mild Cognitive Impairment Among Those Free at Baseline
Time Frame: From baseline through year 3
Mild cognitive impairment based on central adjudication of test scores with input from proxies. Based on test scores administered annually across 3 years.
From baseline through year 3
Executive Function
Time Frame: From baseline through year 3
Average of z-scores for the following tests: Oral Trail Making Test - B (log-transformed), Category Verbal Fluency, Letter Verbal Fluency, Number Span Test (Backwards and Forward). Higher (positive) scores reflect better performance. Linear contrast of scores collected at baseline, year 1, year 2, and year 3: (z1+z2+z3)/3 - z0)
From baseline through year 3
Episodic Memory
Time Frame: From baseline through year 3
Average z-scores from Telephone Interview for Cognitive Status-modified Delayed Word List, Story Immediate Recall, Story Delayed Recall. Higher (positive) scores reflect better performance. Annual test administrations.
From baseline through year 3
Executive Function
Time Frame: From baseline through year 3
Average of z-scores for the following tests: Oral Trail Making Test - B (log-transformed), Category Verbal Fluency, Letter Verbal Fluency, Number Span Test (Backwards and Forward). Higher (positive) scores reflect better performance. Tests administered annually.
From baseline through year 3
Episodic Memory
Time Frame: From baseline through year 3
Average z-scores from Telephone Interview for Cognitive Status-modified Delayed Word List, Story Immediate Recall, Story Delayed Recall. Higher (positive) scores reflect better performance.
From baseline through year 3

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Wake Forest University Health Sciences

Collaborators

National Institute on Aging (NIA)
Brigham and Women's Hospital

Investigators

  • Principal Investigator: Stephen R Rapp, PhD, Co-Investigator Wake Forest School of Medicine
  • Principal Investigator: Sally A Shumaker, PhD, Co-Investigator Wake Forest School of Medicine
  • Principal Investigator: JoAnn E Manson, MD, Parent Study Principal Investigator/COSMOS Mind Co-Investigator Brigham and Women's Hospital
  • Principal Investigator: Howard Sesso, SCD, MPH, Parent Study Principal Investigator/COSMOS Mind Co-Investigator Brigham and Women's Hospital
  • Principal Investigator: Mark A Espeland, PhD, Wake Forest University Health Sciences
  • Principal Investigator: Laura D Baker, PhD, Wake Forest University Health Sciences

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2016

Primary Completion (Actual)

February 12, 2021

Study Completion (Actual)

February 12, 2021

Study Registration Dates

First Submitted

January 20, 2017

First Submitted That Met QC Criteria

January 25, 2017

First Posted (Estimated)

January 27, 2017

Study Record Updates

Last Update Posted (Actual)

August 22, 2023

Last Update Submitted That Met QC Criteria

August 18, 2023

Last Verified

May 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IRB00037753
  • 1R01AG050657-01A1 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

COSMOS-Mind and COSMOS (parent trial, PI: Manson and Sesso) have data transfer procedures and protocols in place which use password protection and encryption, to permit seamless and secure exchange of information. Safety monitoring will be completed through the parent trial. The COSMOS-Mind staff will send all adverse events reported to them to the parent trial for reporting and follow-up. This data will be sent electronically only to approved users through a protected network.

IPD Sharing Time Frame

after completion of study

IPD Sharing Access Criteria

Data have been submitted to the parent COSMOS trial for merging with phenotypes and distribution.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • ICF

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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