Cocoa Supplementation, Inflammaging, and Epigenetic Aging

Study Overview
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Brief Summary
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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. (-)-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. This ancillary study is being conducted among participants in COSMOS and will examine whether the cocoa extract supplement or the multivitamin supplement has an anti-aging effect (epigenetic aging and inflammaging) and examining these findings in the context of CVD risk factors and outcomes.

Official Title
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Effect of Randomized Cocoa Supplementation on Inflammaging and Epigenetic Aging

Conditions
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Aging, Inflammation, Cardiovascular Diseases

Intervention / Treatment
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* Dietary Supplement: Cocoa extract
* Dietary Supplement: Multivitamin
* Dietary Supplement: Cocoa extract placebo
* Dietary Supplement: Multivitamin placebo


Participation Criteria
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Eligibility Criteria
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Participants in COSMOS (NCT02422745) who meet the following criteria are eligible to participate in this ancillary study: Inclusion Criteria: Provided blood samples at baseline, Year 1, and Year 2 of follow-up. Opted to use EMSI for longitudinal blood collections, during which seated BPs were additionally measured. Exclusion Criteria: • Did not collect blood samples at baseline, Year 1, or Year 2 of follow-up.

Ages Eligible for Study
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Minimum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Cocoa extract + multivitamin<br>Two capsules/day for 600 mg/day of cocoa flavanols One tablet/day of multivitamin | Dietary Supplement: Cocoa extract<br>* 2 capsules each day containing a total of 500 mg cocoa flavanols, including 80 mg (-)-epicatechin, and 50 mg theobromine<br>Dietary Supplement: Multivitamin<br>* Multivitamin<br>|
| Active Comparator: Cocoa extract + multivitamin placebo<br>Two capsules/day for 600 mg/day of cocoa flavanols Multivitamin placebo | Dietary Supplement: Cocoa extract<br>* 2 capsules each day containing a total of 500 mg cocoa flavanols, including 80 mg (-)-epicatechin, and 50 mg theobromine<br>Dietary Supplement: Multivitamin placebo<br>* Multivitamin placebo<br>|
| Active Comparator: Cocoa extract placebo + multivitamin<br>Cocoa extract placebo One tablet/day of multivitamin | Dietary Supplement: Multivitamin<br>* Multivitamin<br>Dietary Supplement: Cocoa extract placebo<br>* Cocoa extract placebo<br>|
| Placebo Comparator: Cocoa extract placebo + multivitamin placebo<br>Cocoa extract placebo Multivitamin placebo | Dietary Supplement: Cocoa extract placebo<br>* Cocoa extract placebo<br>Dietary Supplement: Multivitamin placebo<br>* Multivitamin placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Epigenetic age acceleration | A cumulative epigenetic aging index (DNAm age) that predicts DNAm age will be calculated. The residual from regressing DNAm age on chronological age provides a measure of epigenetic age acceleration. | 2 years | 
| Inflammaging | An index constructed using several inflammation markers reflecting inflammaging. | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Blood pressure | Systolic and diastolic blood pressure in mmHg. | 2 years | 
| Body mass index | Body mass index in kg/m2 will be calculated using height and weight | 2 years | 
| Pulse wave velocity | Pulse wave velocity in m/s from the carotid to the femoral artery will be measured. | 2 years |