COSMOS Web: Investigating the Effects of Cocoa Flavanol on Cognition Assessed Online

• ClinicalTrials.gov Identifier: NCT04582617
• Recruitment Status: Active, not recruiting
• First Posted: October 9, 2020
• Last Update Posted: January 22, 2021
• Sponsor: Columbia University
• Collaborators: Brigham and Women's Hospital; Fred Hutchinson Cancer Research Center; Mars, Inc.
• Information provided by (Responsible Party): Adam Brickman, Columbia University

Tracking Information

• First Submitted Date: October 2, 2019
• First Posted Date: October 9, 2020
• Last Update Posted Date: January 22, 2021
• Actual Study Start Date: August 26, 2016
• Estimated Primary Completion Date: November 30, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 5, 2020)

ModRey: 1-Year Change in Immediate Recall/Learning/Episodic Memory [ Time Frame: 1-year follow-up ]

A measure of verbal memory. The change in the number of words recalled immediately on the ModRey task (Hale et al., 2019), after one year of cocoa extract/placebo intervention.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: January 17, 2021)

• ModRey: Longitudinal Change in Immediate Recall/Learning [ Time Frame: 2-year and 3-year follow-ups ]
  A measure of verbal memory. Change in number of words recalled immediately on the ModRey task.
• ModBent [ Time Frame: 1-year, 2-year and 3-year follow-ups ]
  A measure of pattern separation/object recognition. Change in the mean response time on correct rejection trials on a delayed recognition task.
• Flanker: Directional Flanker Effect [ Time Frame: 1-year, 2-year and 3-year follow-ups ]
  A measure of executive control. Change in the difference in reaction time (in ms) between directionally congruent and directional incongruent trials in a Flanker task.
• Spatial Reconstruction: Distortion [ Time Frame: 1-year, 2-year and 3-year follow-ups ]
  A measure of spatial memory. Change in the proportion of stimulus pairs where their relative locations are reconstructed differently than originally shown
• Self-Reported Memory Change [ Time Frame: 1-year, 2-year and 3-year follow-ups ]
  Self-report of memory change in the last year, on a scale of 1-7
• In-clinic ModBent [ Time Frame: 2-year follow-up ]
  Change in performance on the ModBent task, administered in-clinic to a subset of 200 participants
• Interaction of Baseline Diet & Intervention on the ModRey [ Time Frame: 1-year, 2-year and 3-year follow-ups ]
  Interaction of baseline diet (as assessed by the Food Frequency Questionnaire) with the flavanol/multivitamin interventions on the ModRey, a measure of verbal memory (change in number of words recalled)
• Hippocampal volume change [ Time Frame: 2-year follow-up ]
  Change in hippocampus volume (in cubic mm) in subset of participants with in-clinic MRI scan
• Global cortical thickness change [ Time Frame: 2-year follow-up ]
  Change in average cortical thickness in the whole brain (in mm) in subset of participants with in-clinic MRI scan
• Hippocampal cerebral blood volume change [ Time Frame: 2-year follow-up ]
  Change in cerebral blood volume in the hippocampus (in cubic mm) in subset of participants with in-clinic MRI scan
• Proportions of words recalled on in-clinic list learning task [ Time Frame: 2-year follow-up ]
  Proportions of words recalled on list learning task for subset of participants with in-clinic cognitive testing

Original Secondary Outcome Measures (submitted: October 5, 2020)

• ModRey: Longitudinal Change in Immediate Recall/Learning [ Time Frame: 2-year and 3-year follow-ups ]
  A measure of verbal memory. Change in number of words recalled immediately on the ModRey task.
• ModBent [ Time Frame: 1-year, 2-year and 3-year follow-ups ]
  A measure of pattern separation/object recognition. Change in the mean response time on correct rejection trials on a delayed recognition task.
• Flanker: Directional Flanker Effect [ Time Frame: 1-year, 2-year and 3-year follow-ups ]
  A measure of executive control. Change in the difference in reaction time (in ms) between directionally congruent and directional incongruent trials in a Flanker task.
• Spatial Reconstruction: Distortion [ Time Frame: 1-year, 2-year and 3-year follow-ups ]
  A measure of spatial memory. Change in the proportion of stimulus pairs where their relative locations are reconstructed differently than originally shown
• Self-Reported Memory Change [ Time Frame: 1-year, 2-year and 3-year follow-ups ]
  Self-report of memory change in the last year, on a scale of 1-7
• In-clinic ModBent [ Time Frame: 2-year follow-up ]
  Change in performance on the ModBent task, administered in-clinic to a subset of 200 participants
• Interaction of Baseline Diet & Intervention on the ModRey [ Time Frame: 1-year, 2-year and 3-year follow-ups ]
  Interaction of baseline diet (as assessed by the Food Frequency Questionnaire) with the flavanol/multivitamin interventions on the ModRey, a measure of verbal memory (change in number of words recalled)
• Hippocampal volume change [ Time Frame: 2-year follow-up ]
  Change in hippocampus volume (in cubic millimeters) in subset of participants with in-clinic MRI scan
• Global cortical thickness change [ Time Frame: 2-year follow-up ]
  Change in average cortical thickness in the whole brain (in milimeters) in subset of participants with in-clinic MRI scan
• Hippocampal cerebral blood volume change [ Time Frame: 2-year follow-up ]
  Change in cerebral blood volume in the hippocampus (in cubic millimeters) in subset of participants with in-clinic MRI scan
• Proportions of words recalled on in-clinic list learning task [ Time Frame: 2-year follow-up ]
  Proportions of words recalled on list learning task for subset of participants with in-clinic cognitive testing

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: COSMOS Web: Investigating the Effects of Cocoa Flavanol on Cognition Assessed Online
• Official Title: COSMOS Web: Investigating the Effects of Cocoa Flavanol on Cognition Assessed Online
• Brief Summary: The COcoa Supplement and Multivitamin Outcomes Study (COSMOS; NCT02422745) is a randomized clinical trial of cocoa extract supplement (containing a total of 600 mg/d flavanols, including 80 mg (-)-epicatechin), and/or 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. This ancillary study (COSMOS Web) is being conducted among a subset of participants in COSMOS and will examine whether the cocoa extract supplements affects cognitive function in older adults.

Detailed Description

The goal of the COSMOS Web study is to determine whether a dietary intervention with flavanol-containing cocoa extract has an effect on cognitive function in older adults (age 60+). The study will be conducted in a subset of 4000 participants from the COSMOS study(NCT02422745). The investigators' recent work (Sloan et al., submitted) showed that cocoa flavanol consumption over 12 weeks led to improvements in immediate recall on the ModRey verbal memory task in healthy older adults.

In COSMOS Web, the investigators are testing the effect of a dietary intervention with flavanol-containing cocoa extract on a range of aging-related cognitive measures, as assessed through a novel online-administered test battery, in a cohort of older participants. Change in ModRey immediate recall performance over 1 year of cocoa extract consumption will be our primary outcome measure. Secondary endpoints will include change in ModRey performance at 2- and 3-year follow-up, and change in performance tests of a novel object recognition task, executive function/working memory, and spatial memory at 1-, 2-, and 3- years follow-up. This study will explore whether baseline measures of cognition and nutritional status can predict differential effects of the cocoa extract supplementation. This study will also explore the effect of multivitamin intake on the primary and secondary outcomes noted above and test whether multivitamin intake interacts with flavanol intake from cocoa extract to enhance or mitigate effects on cognitive outcomes. In a subset of participants evaluated in person, this study will examine the impact of cocoa extract intake and explore the main and interacting effects of multivitamins on cognitive changes and brain structure and function appreciated with magnetic resonance imaging over a 2-year period.

Leveraging the COSMOS study, which has randomized 21,444 older adult participants into cocoa extract and placebo interventions, the study team at Brigham and Women's Hospital, who administer the parent COSMOS trial, are recruiting ~4000 older adult volunteers to participate in COSMOS Web (this study) an online cognitive testing battery developed by the team at Columbia University. These 4000 participants will complete an initial online cognitive assessment and additional assessments after one, two, and three years of follow-up. In addition, approximately 200 COSMOS Web participants who live in the Boston area will complete clinic-based study visits at the Clinical and Translational Science Center at Brigham and Women's Hospital. During that visit, they will complete a neuropsychological test battery, for comparison to their performance online. This study will examine the impact of dietary interventions with cocoa extract and explore the main and interacting effects of multivitamin intake on cognitive changes and brain structure and function appreciated with magnetic resonance imaging over a 2-year period.

• Study Type: Interventional
• Study Phase: Phase 4
• Study Design: Allocation: Randomized; Intervention Model: Factorial Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Prevention

Condition

• Aging
• Cognitive Change

Intervention

• 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: Cocoa Extract Placebo
  Cocoa extract placebo
• Dietary Supplement: Multivitamin
  Multivitamin
• Dietary Supplement: Multivitamin placebo
  Multivitamin placebo

Study Arms

• 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: Cocoa Extract Placebo
  • Dietary Supplement: Multivitamin
• Placebo Comparator: Cocoa extract placebo + multivitamin placebo
  Interventions:

  • Dietary Supplement: Cocoa Extract Placebo
  • Dietary Supplement: Multivitamin placebo

Publications *

• Brickman AM, Khan UA, Provenzano FA, Yeung LK, Suzuki W, Schroeter H, Wall M, Sloan RP, Small SA. Enhancing dentate gyrus function with dietary flavanols improves cognition in older adults. Nat Neurosci. 2014 Dec;17(12):1798-803. doi: 10.1038/nn.3850. Epub 2014 Oct 26.
• Hale C, Last BS, Meier IB, Yeung LK, Budge M, Sloan RP, Small SA, Brickman AM. The ModRey: An Episodic Memory Test for Nonclinical and Preclinical Populations. Assessment. 2019 Sep;26(6):1154-1161. doi: 10.1177/1073191117723113. Epub 2017 Aug 11.
• Sloan RP, Wall M, Yeung LK, Feng T, Feng X, Provenzano F, Schroeter H, Lauriola V, Brickman AM, Small SA. Insights into the role of diet and dietary flavanols in cognitive aging: results of a randomized controlled trial. Sci Rep. 2021 Feb 15;11(1):3837. doi: 10.1038/s41598-021-83370-2.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: October 5, 2020): 3947
• Original Actual Enrollment: Same as current
• Estimated Study Completion Date: November 30, 2021
• Estimated Primary Completion Date: November 30, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Inclusion Criteria:

• Willingness to participate
• Email and internet access via computer

Exclusion Criteria:

* Analog to COSMOS parent trial

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 60 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04582617
• Other Study ID Numbers: AAAQ8029
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: Researchers interested in study data may contact the study principal investigators to request access. Data requests must be submitted in writing for approval by qualified individuals; they will be reviewed by study investigators. External investigators who are granted access to data for analysis must identify a Cosmos Web investigator, who will participate in analyses and manuscript preparation as a co-author. Researchers interested in accessing data related to the Cosmos parent trial (NCT02422745) should contact the administrators of that study.
• Supporting Materials: Study Protocol
• Supporting Materials: Informed Consent Form (ICF)
• Time Frame: After completion of study
• Access Criteria: Cosmos-Web Project Proposal Form Approved by Dr. Brickman

• Responsible Party: Adam Brickman, Columbia University
• Study Sponsor: Columbia University

Collaborators

• Brigham and Women's Hospital
• Fred Hutchinson Cancer Research Center
• Mars, Inc.

Investigators

• Principal Investigator: Adam M Brickman, PhD; Columbia University
• Principal Investigator: Scott A Small, MD; Columbia University

• PRS Account: Columbia University
• Verification Date: January 2021