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

• ClinicalTrials.gov Identifier: NCT03205202
• Recruitment Status: Enrolling by invitation
• First Posted: July 2, 2017
• Last Update Posted: September 17, 2021
• Sponsor: Brigham and Women's Hospital
• Information provided by (Responsible Party): William G. Christen, Brigham and Women's Hospital

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Cataract; Age Related Macular Degeneration	Dietary Supplement: Cocoa extract; Dietary Supplement: Multivitamin; Dietary Supplement: Cocoa extract placebo; Dietary Supplement: Multivitamin placebo	Phase 4

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 21442 participants
• Allocation: Randomized
• Intervention Model: Factorial Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Prevention
• Official Title: Cataract and AMD in a Trial of a Multivitamin and Cocoa Extract (COSMOS-Eye)
• Actual Study Start Date: June 1, 2015
• Estimated Primary Completion Date: May 2022
• Estimated Study Completion Date: October 2022

Arms and Interventions

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: Cocoa extract; Dietary Supplement: Multivitamin
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: Cocoa extract placebo; Dietary Supplement: Multivitamin placebo

Outcome Measures

Primary Outcome Measures :

1. Cataract [ Time Frame: 5 years ]
   Incident age-related cataract responsible for a reduction in best-corrected visual acuity to 20/30 or worse
2. Total AMD events [ Time Frame: 5 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 :

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

Eligibility Criteria

• Ages Eligible for Study: 60 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

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.

Contacts and Locations

No Contacts or Locations Provided

More Information

• Responsible Party: William G. Christen, Associate Professor, Brigham and Women's Hospital
• ClinicalTrials.gov Identifier: NCT03205202
• Other Study ID Numbers: 2016P001612
• First Posted: July 2, 2017
• Last Update Posted: September 17, 2021
• Last Verified: September 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Cataract; Macular Degeneration; Lens Diseases; Eye Diseases; Retinal Degeneration; Retinal Diseases