Clinical trial NCT04582617: Investigating the Effects of Cocoa Flavanol on Cognition Assessed Online
Official title: COSMOS Web: Investigating the Effects of Cocoa Flavanol on Cognition Assessed Online
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Aging
Cognitive Change
Keywords: Cognitive Function
Cognitive Change
Aging
ModRey
Cocoa Extract
Multivitamin
Hippocampus
Executive Function
Verbal Memory
Spatial Memory
Lead sponsor: Columbia University
Sponsor class: OTHER
Collaborators: name: Brigham and Women's Hospital
name: Fred Hutchinson Cancer Center
name: Mars, Inc.
First posted: 2020-10-09
Enrollment: 3959
Sex: ALL
Minimum age (years): 65
Standard ages: OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: PREVENTION

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.

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.

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

Primary outcomes:
measure: ModRey: 1-Year Change in Immediate Recall/Learning/Episodic Memory
timeFrame: 1-year follow-up
Secondary outcomes:
measure: ModRey: Longitudinal Change in Immediate Recall/Learning
timeFrame: 2-year and 3-year follow-ups
measure: ModBent
timeFrame: 1-year, 2-year and 3-year follow-ups
measure: Flanker: Directional Flanker Effect
timeFrame: 1-year, 2-year and 3-year follow-ups
measure: Spatial Reconstruction: Distortion
timeFrame: 1-year, 2-year and 3-year follow-ups
measure: Self-Reported Memory Change
timeFrame: 1-year, 2-year and 3-year follow-ups
measure: In-clinic ModBent
timeFrame: 2-year follow-up
measure: Interaction of Baseline Diet & Intervention on the ModRey
timeFrame: 1-year, 2-year and 3-year follow-ups
measure: Hippocampal volume change
timeFrame: 2-year follow-up
measure: Global cortical thickness change
timeFrame: 2-year follow-up
measure: Hippocampal cerebral blood volume change
timeFrame: 2-year follow-up
measure: Proportions of words recalled on in-clinic list learning task
timeFrame: 2-year follow-up
Other outcomes:
Locations:
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: New York
country: United States
facility: Columbia University Irving Medical Center
state: New York
Study officials:
affiliation: Columbia University
name: Adam M. Brickman, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.