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

• ClinicalTrials.gov Identifier: NCT04582617
• Recruitment Status: Completed
• First Posted: October 9, 2020
• Last Update Posted: April 7, 2023
• Sponsor: Columbia University
• Collaborators: Brigham and Women's Hospital; Fred Hutchinson Cancer Center; Mars, Inc.
• Information provided by (Responsible Party): Columbia University

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Aging; Cognitive Change	Dietary Supplement: Cocoa Extract; Dietary Supplement: Cocoa Extract Placebo; Dietary Supplement: Multivitamin; Dietary Supplement: Multivitamin placebo	Not Applicable

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 3959 participants
• Allocation: Randomized
• Intervention Model: Factorial Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Prevention
• Official Title: COSMOS Web: Investigating the Effects of Cocoa Flavanol on Cognition Assessed Online
• Actual Study Start Date: August 26, 2016
• Actual Primary Completion Date: December 31, 2020
• Actual Study Completion Date: December 31, 2020

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. 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.

Secondary Outcome Measures :

1. 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.
2. 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.
3. 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.
4. 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
5. 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
6. 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
7. 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)
8. 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
9. 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
10. 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
11. 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

Eligibility Criteria

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

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

Contacts and Locations

Locations

United States, Massachusetts

Brigham and Women's Hospital

Boston, Massachusetts, United States, 02115

United States, New York

Columbia University Irving Medical Center

New York, New York, United States, 10032

Sponsors and Collaborators

Columbia University

Brigham and Women's Hospital

Fred Hutchinson Cancer Center

Mars, Inc.

Investigators

• Principal Investigator: Adam M. Brickman, PhD; Columbia University

More Information

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.

• Responsible Party: Columbia University
• ClinicalTrials.gov Identifier: NCT04582617
• Other Study ID Numbers: AAAQ8029
• First Posted: October 9, 2020
• Last Update Posted: April 7, 2023
• Last Verified: April 2023

Individual Participant Data (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; Informed Consent Form (ICF)
• Time Frame: After completion of study
• Access Criteria: Cosmos-Web Project Proposal Form Approved by Dr. Brickman

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

Keywords provided by Columbia University:

Cognitive Function; Cognitive Change; Aging; ModRey; Cocoa Extract; Multivitamin; Hippocampus; Executive Function; Verbal Memory; Spatial Memory