CataractPhase 4COSMOS-EyeNCT03205202
Cataract and AMD in a Trial of a Multivitamin and Cocoa Extract
A Phase 4 study testing Cocoa extract and Multivitamin in people with Cataract and Age Related Macular Degeneration, run by Brigham and Women's Hospital.
Trial 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… Read more about this study
- Who is it for?
- Ages 60 years and olderHealthy volunteers can take part
- Conditions the study is for
- Cataract, Age Related Macular Degeneration
- What is being tested?
- Cocoa extract and Multivitamin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 21,442 participants
- Where
- No sites listed yet
- Study dates
- 1 Jun 2015to Oct 2022
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 60 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
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.
About this study
Official title: 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.
Read the 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.
- Conditions
- Cataract, Age Related Macular Degeneration
- Being tested
- Cocoa extract, Multivitamin, Cocoa extract placebo, Multivitamin placebo
- Medical subject headings
- Cataract, Macular Degeneration
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cocoa extractDietary supplement
MultivitaminDietary supplement
Cocoa extract placeboDietary supplement
Multivitamin placeboDietary supplement
| Study group | Role | What they receive |
|---|---|---|
| Cocoa extract + multivitamin | Active comparator | 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 Receives: Dietary Supplement: Cocoa extract; Dietary Supplement: Multivitamin |
| Cocoa extract + multivitamin placebo | Active comparator | 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 Receives: Dietary Supplement: Cocoa extract; Dietary Supplement: Multivitamin placebo |
| Cocoa extract placebo + multivitamin | Active comparator | Dietary Supplement: Multivitamin
Dietary Supplement: Cocoa extract placebo Receives: Dietary Supplement: Multivitamin; Dietary Supplement: Cocoa extract placebo |
| Cocoa extract placebo + multivitamin placebo | Placebo comparator | Dietary Supplement: Cocoa extract placebo
Dietary Supplement: Multivitamin placebo Receives: Dietary Supplement: Cocoa extract placebo; Dietary Supplement: Multivitamin placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cataract
Incident age-related cataract responsible for a reduction in best-corrected visual acuity to 20/30 or worse
Measured: 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
Measured: 5 years
Secondary outcomes (5)
Cataract surgery
Incident extraction of an age-related lens opacity
Measured: 5 years
Total cataract events
Composite of incident cataract plus cataract surgery among participants with prevalent cataract at baseline
Measured: 5 years
AMD
Incident AMD with or without vision loss
Measured: 5 years
Visually-significant AMD
Incident AMD responsible for a reduction in best-corrected visual acuity to 20/30 or worse
Measured: 5 years
Advanced AMD
Incident advanced AMD (neovascular or geographic atrophy)
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jul 2017
- Study start1 Jun 2015
- Primary completionMay 2022 (estimated)
- Study completionOct 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for CataractStudies of the same condition, open and under way.
- More trials run by Brigham and Women's HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 21,442 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Brigham and Women's Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, William G. Christen, Brigham and Women's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03205202
- Sponsor's protocol ID
- 2016P001612
- Acronym
- COSMOS-Eye
- Status last verified
- Sep 2021
- First submitted
- 29 Jun 2017
- Last updated
- 17 Sep 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Christen WG, Rist PM, Moorthy MV, Smith DC, Holman B, Clar A, Glynn RJ, Mares JA, Sobrin L, Shadyab AH, Allison MA, Millen AE, Manson JE, Sesso HD; COSMOS Research Group. Cocoa Flavanol Supplementation and Risk of Age-Related Macular Degeneration: An Ancillary Study of the COSMOS Randomized Clinical Trial. JAMA Ophthalmol. 2025 May 1;143(5):429-437. doi: 10.1001/jamaophthalmol.2025.0353.
PubMed 40146119
Study at a glance
From the registry record, last updated by the sponsor on 17 Sep 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cataract and AMD in a Trial of a Multivitamin and Cocoa Extract (COSMOS-Eye)
- ClinicalTrials.gov ID
- NCT03205202
- Acronym / sponsor ID
- COSMOS-Eye / 2016P001612
- Conditions
- Cataract, Age Related Macular Degeneration
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 21,442 participants (estimated)
- Lead sponsor
- Brigham and Women's HospitalUniversity, hospital or other
- Study start
- 1 Jun 2015 (actual)
- Primary completion
- May 2022 (estimated)
- Study completion
- Oct 2022 (estimated)
- First posted
- 2 Jul 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Double blind (participant, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Cocoa extract + multivitamin | Active comparator | Dietary Supplement: Cocoa extract, Dietary Supplement: MultivitaminDietary 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 placebo | Active comparator | Dietary Supplement: Cocoa extract, Dietary Supplement: Multivitamin 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 | Active comparator | Dietary Supplement: Multivitamin, Dietary Supplement: Cocoa extract placeboDietary Supplement: Multivitamin Dietary Supplement: Cocoa extract placebo |
| Cocoa extract placebo + multivitamin placebo | Placebo comparator | Dietary Supplement: Cocoa extract placebo, Dietary Supplement: Multivitamin placeboDietary Supplement: Cocoa extract placebo Dietary Supplement: Multivitamin placebo |
Who may qualify
- Ages
- 60 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Cocoa extract | Dietary supplement | Cocoa extract + multivitamin, Cocoa extract + multivitamin placebo |
| Multivitamin | Dietary supplement | Cocoa extract + multivitamin, Cocoa extract placebo + multivitamin |
| Cocoa extract placebo | Dietary supplement | Cocoa extract placebo + multivitamin, Cocoa extract placebo + multivitamin placebo |
| Multivitamin placebo | Dietary supplement | Cocoa extract + multivitamin placebo, Cocoa extract placebo + multivitamin placebo |
Primary outcome
Cataract
Time frame: 5 years
Incident age-related cataract responsible for a reduction in best-corrected visual acuity to 20/30 or worse
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
5 secondary outcomes
Cataract surgery
Time frame: 5 years
Total cataract events
Time frame: 5 years
AMD
Time frame: 5 years
Visually-significant AMD
Time frame: 5 years
Advanced AMD
Time frame: 5 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Sep 2021.
- Derived from this study: PubMed 40146119Christen WG, Rist PM, Moorthy MV, Smith DC, Holman B, Clar A, Glynn RJ, Mares JA, Sobrin L, Shadyab AH, Allison MA, Millen AE, Manson JE, Sesso HD; COSMOS Research Group. Cocoa Flavanol Supplementation and Risk of Age-Related Macular Degeneration: An Ancillary Study of the COSMOS Randomized Clinical Trial. JAMA Ophthalmol. 2025 May 1;143(5):429-437. doi: 10.1001/jamaophthalmol.2025.0353.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Cocoa extract and Multivitamin in people with Cataract and Age Related Macular Degeneration, run by Brigham and Women's Hospital.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 17 Sep 2021. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Cataract (time frame: 5 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03205202, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Sep 2021.