Cataract and AMD in a Trial of a Multivitamin and Cocoa Extract (COSMOS-Eye)

Cataract and AMD in a Trial of a Multivitamin and Cocoa Extract (COSMOS-Eye)

COSMOS-Eye is an ancillary study of the COcoa-Supplement and Multivitamins Outcomes Study (COSMOS; NCT02422745). COSMOS 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 reduces the risk of cataract and AMD, two leading causes of visual impairment in US men and women.

Study Overview

• Status: Enrolling by invitation
• Conditions: Cataract; Age Related Macular Degeneration
• Intervention / Treatment: Dietary supplement: Multivitamin; Dietary supplement: Cocoa extract; Dietary supplement: Multivitamin placebo; Dietary supplement: Cocoa extract placebo

Detailed Description

COSMOS-Eye is an ancillary study of cataract and AMD utilizing resources and data from the COcoa-Supplement and Multivitamins Outcomes Study (COSMOS), a randomized, double-blind, placebo-controlled, 2x2 factorial trial of a high-quality cocoa extract supplement (Mars Symbioscience) and Centrum Silver multivitamin (Pfizer) in the prevention of cardiovascular disease and cancer among 12,000 women aged ≥65 years and 6,000 men aged ≥60 years.

Women will be recruited among active Women's Health Initiative (WHI) Extension Study participants, and men will be recruited among non-randomized respondents to the VITamin D and OmegA-3 Trial (VITAL). Women who responded but were not randomized into VITAL will also be included as well as other women and men who express interest in research being conducted at Brigham and Women's Hospital.

Participants will take three pills each day: two capsules that contain either cocoa extract or cocoa extract placebo, and one tablet that contains either multivitamin or multivitamin placebo. Participants will receive their study pills in convenient calendar packs via U.S. mail.

Participants also will be asked to complete short mailed questionnaires each year. The questionnaires ask about health; lifestyle habits, such as diet, physical activity, and smoking; use of medications and dietary supplements; family history of illness and new medical diagnoses including cataract and AMD.

Participants who report cataract or AMD will be asked to provide contact information for their eye doctor(s) as well as written consent to obtain the medical records. Eye doctors will be contacted by mail and asked to complete a cataract (or AMD) questionnaire or, alternatively, forward a complete copy of the patient's medical records pertaining to the diagnosis.

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 (Anticipated): 21442
• Phase: Phase 4

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Participants in COSMOS who 1) report a diagnosis of cataract or AMD, or extraction of cataract, and 2) provide written consent to obtain the medical records for the reported endpoint, are eligible for this ancillary study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: FACTORIAL
• 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	Dietary supplement: Multivitamin; Dietary supplement: Cocoa extract
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	Dietary supplement: Cocoa extract; Dietary supplement: Multivitamin placebo
ACTIVE_COMPARATOR: Cocoa extract placebo + multivitamin; Dietary Supplement: Multivitamin Dietary Supplement: Cocoa extract placebo	Dietary supplement: Multivitamin; Dietary supplement: Cocoa extract placebo
PLACEBO_COMPARATOR: Cocoa extract placebo + multivitamin placebo; Dietary Supplement: Cocoa extract placebo Dietary Supplement: Multivitamin placebo	Dietary supplement: Multivitamin placebo; Dietary supplement: Cocoa extract placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cataract	Incident age-related cataract responsible for a reduction in best-corrected visual acuity to 20/30 or worse	5 years
Total AMD events	Composite of incident AMD plus cases of progression to advanced AMD (neovascular AMD plus central geographic atrophy) among participants with prevalent AMD at baseline	5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cataract surgery	Incident extraction of an age-related lens opacity	5 years
Total cataract events	Composite of incident cataract plus cataract surgery among participants with prevalent cataract at baseline	5 years
AMD	Incident AMD with or without vision loss	5 years
Visually-significant AMD	Incident AMD responsible for a reduction in best-corrected visual acuity to 20/30 or worse	5 years
Advanced AMD	Incident advanced AMD (neovascular or geographic atrophy)	5 years

Collaborators and Investigators

• Sponsor: Brigham and Women's Hospital

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 1, 2015
• Primary Completion (ANTICIPATED): May 1, 2022
• Study Completion (ANTICIPATED): October 1, 2022

Study Registration Dates

• First Submitted: June 29, 2017
• First Submitted That Met QC Criteria: June 29, 2017
• First Posted (ACTUAL): July 2, 2017

Study Record Updates

• Last Update Posted (ACTUAL): September 17, 2021
• Last Update Submitted That Met QC Criteria: September 13, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Eye Diseases; Retinal Degeneration; Retinal Diseases; Lens Diseases; Macular Degeneration; Cataract
• Other Study ID Numbers: 2016P001612

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No