Investigating the Effects of Cocoa Flavanol on Cognition Assessed Online (COSMOS-Web)

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

The 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 (-)-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.

Study Overview

• Status: Completed
• Conditions: Cognitive Change; Aging
• Intervention / Treatment: Dietary supplement: Cocoa Extract; Dietary supplement: Multivitamin; Dietary supplement: Multivitamin placebo; Dietary supplement: Cocoa Extract Placebo

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 (Modified Rey Auditory Verbal Learning Test) 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 21,442 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.

After the COSMOS trial began, an advanced method to analyze cocoa flavanols was accredited by AOAC International as a First Action Official Method of Analysis (https://doi.org/10.1093/jaoacint/qsaa132). 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, we 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.

• Study Type: Interventional
• Enrollment (Actual): 3959
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital
  • New York
    • New York, New York, United States, 10032
      • Columbia University Irving Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years and older (Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Cocoa extract + multivitamin	Dietary supplement: Cocoa Extract; 2 capsules each day containing a total of 500 mg cocoa flavanols, including 80 mg (-)-epicatechin, and 50 mg theobromine; Dietary supplement: Multivitamin; Multivitamin
Active Comparator: Cocoa extract + multivitamin placebo	Dietary supplement: Cocoa Extract; 2 capsules each day containing a total of 500 mg cocoa flavanols, including 80 mg (-)-epicatechin, and 50 mg theobromine; Dietary supplement: Multivitamin placebo; Multivitamin placebo
Active Comparator: Cocoa extract placebo + multivitamin	Dietary supplement: Multivitamin; Multivitamin; Dietary supplement: Cocoa Extract Placebo; Cocoa extract placebo
Placebo Comparator: Cocoa extract placebo + multivitamin placebo	Dietary supplement: Multivitamin placebo; Multivitamin placebo; Dietary supplement: Cocoa Extract Placebo; Cocoa extract placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ModRey: 1-Year Change in Immediate Recall/Learning/Episodic Memory	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.	1-year follow-up

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Columbia University
• Collaborators: Brigham and Women's Hospital; Fred Hutchinson Cancer Center; Mars, Inc.
• Investigators: Principal Investigator: Adam M. Brickman, PhD, Columbia University

Publications and helpful links

General 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.

Study record dates

Study Major Dates

• Study Start (Actual): August 26, 2016
• Primary Completion (Actual): December 31, 2020
• Study Completion (Actual): December 31, 2020

Study Registration Dates

• First Submitted: October 2, 2019
• First Submitted That Met QC Criteria: October 5, 2020
• First Posted (Actual): October 9, 2020

Study Record Updates

• Last Update Posted (Actual): April 7, 2023
• Last Update Submitted That Met QC Criteria: April 6, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: Aging; Hippocampus; Executive Function; Cognitive Function; Cognitive Change; ModRey; Cocoa Extract; Multivitamin; Verbal Memory; Spatial Memory
• Other Study ID Numbers: AAAQ8029

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD 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.
• IPD Sharing Time Frame: After completion of study
• IPD Sharing Access Criteria: Cosmos-Web Project Proposal Form Approved by Dr. Brickman
• 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