Cataract and AMD in a Trial of a Multivitamin and Cocoa Extract

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Cataract, Age Related Macular Degeneration

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 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.

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>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: Cocoa extract<br> <br> Dietary Supplement: Multivitamin<br> <br> |
| Active Comparator: Cocoa extract + multivitamin placebo<br>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<br> <br> Dietary Supplement: Multivitamin placebo<br> <br> |
| Active Comparator: Cocoa extract placebo + multivitamin<br>Dietary Supplement: Multivitamin Dietary Supplement: Cocoa extract placebo | Dietary Supplement: Multivitamin<br> <br> Dietary Supplement: Cocoa extract placebo<br> <br> |
| Placebo Comparator: Cocoa extract placebo + multivitamin placebo<br>Dietary Supplement: Cocoa extract placebo Dietary Supplement: Multivitamin placebo | Dietary Supplement: Cocoa extract placebo<br> <br> Dietary Supplement: Multivitamin placebo<br> <br> |

What is the study measuring?
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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 |