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Completed

NCT Number: NCT03035201

COcoa Supplement and Multivitamin Outcomes Study for the 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.

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Key information

Conditions

Cognitive Impairment Aging Alzheimer Disease Brain Diseases Central Nervous System Diseases Cognition Disorders Cognitive Dysfunction Dementia Mental Disorders Nervous System Diseases Neurocognitive Disorders Neurodegenerative Diseases Tauopathies

Age range

65 year and older

Sex eligibility

All sexes

Study type

Observational

Primary location

Wake Forest School of Medicine

Winston-Salem, North Carolina, 27157, United States

About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

Inclusion criteria

-

  • Men and women 65 years and older.
  • Willingness to participate.
  • Ability to answer questions by phone.

Exclusion criteria

-

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

Treatment and study plan

Primary outcomes

  1. 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).

Secondary outcomes

  1. 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)

  2. 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.

  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.

  4. 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)

  5. 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.

  6. 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.

  7. 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.

Sponsors and collaborators

Lead sponsor

Wake Forest University Health Sciences

Other

Collaborators

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

Registry information

Official study title

COcoa Supplement and Multivitamin Outcomes Study-Mind

Acronym: COSMOS-Mind

Important dates

Study start
2016
Primary completion
2021
Study completion
2021
First posted
Jan 27, 2017
Registry last updated
Aug 22, 2023

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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