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

Phase 4
Conditions
Age Related Macular Degeneration
Cataract
Interventions
Dietary Supplement: Multivitamin
Dietary Supplement: Cocoa extract
Dietary Supplement: Cocoa extract placebo
Dietary Supplement: Multivitamin placebo
Registration Number
NCT03205202
Lead Sponsor
Brigham and Women's Hospital
Brief Summary

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

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.

Recruitment & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
21442
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
FACTORIAL
Arm && Interventions
GroupInterventionDescription
Cocoa extract placebo + multivitaminMultivitaminDietary Supplement: Multivitamin Dietary Supplement: Cocoa extract placebo
Cocoa extract + multivitaminMultivitaminDietary 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
Cocoa extract placebo + multivitaminCocoa extract placeboDietary Supplement: Multivitamin Dietary Supplement: Cocoa extract placebo
Cocoa extract + multivitaminCocoa extractDietary 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
Cocoa extract + multivitamin placeboCocoa extractDietary 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
Cocoa extract + multivitamin placeboMultivitamin placeboDietary 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
Cocoa extract placebo + multivitamin placeboCocoa extract placeboDietary Supplement: Cocoa extract placebo Dietary Supplement: Multivitamin placebo
Cocoa extract placebo + multivitamin placeboMultivitamin placeboDietary Supplement: Cocoa extract placebo Dietary Supplement: Multivitamin placebo
Primary Outcome Measures
NameTimeMethod
Cataract5 years

Incident age-related cataract responsible for a reduction in best-corrected visual acuity to 20/30 or worse

Total AMD events5 years

Composite of incident AMD plus cases of progression to advanced AMD (neovascular AMD plus central geographic atrophy) among participants with prevalent AMD at baseline

Secondary Outcome Measures
NameTimeMethod
Visually-significant AMD5 years

Incident AMD responsible for a reduction in best-corrected visual acuity to 20/30 or worse

Cataract surgery5 years

Incident extraction of an age-related lens opacity

Total cataract events5 years

Composite of incident cataract plus cataract surgery among participants with prevalent cataract at baseline

AMD5 years

Incident AMD with or without vision loss

Advanced AMD5 years

Incident advanced AMD (neovascular or geographic atrophy)

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