Ignite Creation Date:
2024-05-06 @ 3:59 AM
Last Modification Date:
2024-10-26 @ 11:41 AM
Study NCT ID:
NCT02422745
Status:
COMPLETED
Last Update Posted:
2022-07-13
First Post:
2015-04-17
Brief Title:
COcoa Supplement and Multivitamin Outcomes Study
Sponsor:
Brigham and Womens Hospital
Organization:
Brigham and Womens Hospital
Study Overview
Official Title:
COcoa Supplement and Multivitamin Outcomes Study
Status:
COMPLETED
Status Verified Date:
2024-04
Last Known Status:
ACTIVE_NOT_RECRUITING
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
COSMOS
Brief Summary:
The purpose of this study is to determine whether taking daily dietary supplements of cocoa extract containing cocoa flavanols and theobromine from the cocoa bean andor a standard multivitamin reduces the risk of developing cardiovascular disease including heart attack stroke coronary revascularization unstable angina or acute coronary syndrome ACS requiring hospitalization carotid artery surgery and peripheral artery surgery or angioplasty and cardiovascular mortality and cancer
Detailed Description:
The COcoa Supplement and Multivitamin Outcomes Study COSMOS is a randomized clinical trial of cocoa extract supplement containing a total of 600 mgd cocoa flavanols including 80 mg --epicatechins and a standard multivitamin supplement to reduce the risk of cardiovascular disease and cancer among women aged 65 years and older and men aged 60 years and older
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 httpsdoiorg101093jaoacintqsaa132 This updated method relies on a reference material RM8403 recently standardized and made commercially available by the US 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 202005RM8403 to the COSMOS intervention the total cocoa flavanol content of the COSMOS intervention is now 500 mgday Reporting of --epicatechin content remained unaffected Going forward we will therefore apply AOAC 202005RM8403 and report that the COSMOS intervention tested 500 mgday of cocoa flavanols including 80 mg of --epicatechin
Participants in COSMOS were recruited from among Womens Health Initiative WHI Extension Study cohort members non-randomized respondents to mailings for the VITamin D and OmegA-3 TriaL VITAL respondents to nationwide invitational mailings to age-eligible adults and volunteers who learned about the trial through the media or through ResearchMatchorg an electronic recruitment website
Several small randomized trials have demonstrated benefits for cocoa flavanols on intermediate outcomes including blood pressure lipids insulin sensitivity and flow-mediated vasodilation For multivitamins a prior large-scale randomized trial in middle-aged and older men showed a significant reduction in cancer but comparable trial data in women are lacking For both interventions a large-scale clinical trial such as COSMOS could have major clinical and public health implications
Eligible participants have been assigned by chance like a coin toss to one of four groups 1 daily cocoa extract and multivitamin 2 daily cocoa extract and multivitamin placebo 3 daily cocoa extract placebo and multivitamin or 4 daily cocoa extract placebo and multivitamin placebo Participants have an equal chance of being assigned to any of these four groups and a 3 out of 4 chance of receiving at least one active agent
Participants in all groups 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 receive their study pills in convenient calendar packs via US mail
Participants are asked to complete 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 Occasionally participants may receive a phone call from study staff to collect information or clarify responses on the questionnaires
The expected rates for our original primary composite cardiovascular disease CVD endpoint were based on the projected age and sex distribution of the trial cohort and CVD event rates from our previously conducted trials However we determined that the observed rates of CVD endpoints among COSMOS participants were lower than expected due to a younger population of women increasing use of statins and other pharmacotherapies as seen in other recently published clinical trials and the impact of COVID-19 on fewer reports of CVD diagnoses hospitalizations and procedures As a result the COSMOS Data and Safety Monitoring Board DSMB approved a proposal to add three new outcomes to our primary composite CVD endpoint 1 unstable angina or acute coronary syndrome requiring hospitalization 2 carotid artery surgery and 3 peripheral artery surgery or angioplasty These additional CVD outcomes are consistent with the atherosclerotic mechanisms underlying the postulated effects for the randomized interventions COSMOS participants have already provided self-reports of these diagnoses since the start of the COSMOS trial that will be adjudicated via medical records The original primary composite CVD endpoint will still be evaluated as a secondary outcome
At baseline approximately 7000 COSMOS participants provided optional blood and urine samples which will be used to determine whether the study agents significantly change biomarkers and other risk factors related to cardiovascular disease and cancer Selected participants either have specimens collected through mailed specimen collection kits that are returned by the participant or have blood urine blood pressure and anthropometric measurements collected by technicians from Examination Management Services Inc EMSI a national clinical services provider A subgroup of those who provide baseline specimens and measurements are asked to provide follow-up samples and measurements
At baseline and year 2 of the trial approximately 600 participants living within driving distance of Boston Massachusetts provide additional measurements from in-clinic study visits at the Clinical and Translational Science Center CTSC of Brigham and Womens Hospital These visits include cognitive function assessments anthropometrics physical function assessments blood pressure and other measurements The trial will assess whether the study agents significantly affect changes in these variables over time
Primary Hypotheses
1 A cocoa extract supplement will reduce the risk of major cardiovascular events defined as a composite endpoint of myocardial infarction stroke cardiovascular mortality coronary revascularization unstable angina or ACS requiring hospitalization carotid artery surgery and peripheral artery surgery or angioplasty
2 A daily multivitamin will reduce the risk of invasive cancer excluding non-melanoma skin cancer
Secondary Hypotheses
1 Cocoa extract will reduce the risk of a composite endpoint of MI stroke cardiovascular mortality and coronary revascularization
2 Cocoa extract will reduce the risk of invasive cancer excluding non-melanoma skin cancer
3 A daily multivitamin will reduce the risk of major cardiovascular events
4 Cocoa extract andor a daily multivitamin will reduce the combined endpoint of major cardiovascular events plus all-cause mortality
5 Cocoa extract andor a daily multivitamin will reduce the risk of individual cardiovascular events including myocardial infarction stroke cardiovascular mortality coronary revascularization unstable angina or ACS requiring hospitalization carotid artery surgery and peripheral artery surgery or angioplasty and total mortality plus site-specific cancers including breast colorectal and lung cancer
6 A daily multivitamin will reduce the risk of cancer among women and men with a history of cancer at baseline
7 In a subset of equal numbers of female and male COSMOS respondents who provide baseline bloods andor urine samples cocoa extract andor a daily multivitamin will significantly change blood andor urinary levels of flavonoids or their metabolites from baseline to 1 2 or 3 years of follow-up
Tertiary Aim
To assess whether the cocoa extract andor a daily multivitamin exhibit synergistic effects on risk of major cardiovascular events or cancer and if the effects vary by nutritional status or medication use
Aims of Clinical and Translational Science Center CTSC Component
To test whether the cocoa extract andor a daily multivitamin has beneficial effects on
1 Systolic and diastolic blood pressure
2 Pulse wave velocity PWV and central blood pressure indices as measured by pulse wave analysis
3 Cognitive function and memory
4 Physical performance as assessed by balance tests grip strength timed chair stands and walking speed
5 Bone loss in the spine hip and total body as assessed by bone-mineral density BMD and changes in body composition as assessed by dual x-ray absorpiometry DXA
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 httpsdoiorg101093jaoacintqsaa132 This updated method relies on a reference material RM8403 recently standardized and made commercially available by the US 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 202005RM8403 to the COSMOS intervention the total cocoa flavanol content of the COSMOS intervention is now 500 mgday Reporting of --epicatechin content remained unaffected Going forward we will therefore apply AOAC 202005RM8403 and report that the COSMOS intervention tested 500 mgday of cocoa flavanols including 80 mg of --epicatechin
Participants in COSMOS were recruited from among Womens Health Initiative WHI Extension Study cohort members non-randomized respondents to mailings for the VITamin D and OmegA-3 TriaL VITAL respondents to nationwide invitational mailings to age-eligible adults and volunteers who learned about the trial through the media or through ResearchMatchorg an electronic recruitment website
Several small randomized trials have demonstrated benefits for cocoa flavanols on intermediate outcomes including blood pressure lipids insulin sensitivity and flow-mediated vasodilation For multivitamins a prior large-scale randomized trial in middle-aged and older men showed a significant reduction in cancer but comparable trial data in women are lacking For both interventions a large-scale clinical trial such as COSMOS could have major clinical and public health implications
Eligible participants have been assigned by chance like a coin toss to one of four groups 1 daily cocoa extract and multivitamin 2 daily cocoa extract and multivitamin placebo 3 daily cocoa extract placebo and multivitamin or 4 daily cocoa extract placebo and multivitamin placebo Participants have an equal chance of being assigned to any of these four groups and a 3 out of 4 chance of receiving at least one active agent
Participants in all groups 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 receive their study pills in convenient calendar packs via US mail
Participants are asked to complete 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 Occasionally participants may receive a phone call from study staff to collect information or clarify responses on the questionnaires
The expected rates for our original primary composite cardiovascular disease CVD endpoint were based on the projected age and sex distribution of the trial cohort and CVD event rates from our previously conducted trials However we determined that the observed rates of CVD endpoints among COSMOS participants were lower than expected due to a younger population of women increasing use of statins and other pharmacotherapies as seen in other recently published clinical trials and the impact of COVID-19 on fewer reports of CVD diagnoses hospitalizations and procedures As a result the COSMOS Data and Safety Monitoring Board DSMB approved a proposal to add three new outcomes to our primary composite CVD endpoint 1 unstable angina or acute coronary syndrome requiring hospitalization 2 carotid artery surgery and 3 peripheral artery surgery or angioplasty These additional CVD outcomes are consistent with the atherosclerotic mechanisms underlying the postulated effects for the randomized interventions COSMOS participants have already provided self-reports of these diagnoses since the start of the COSMOS trial that will be adjudicated via medical records The original primary composite CVD endpoint will still be evaluated as a secondary outcome
At baseline approximately 7000 COSMOS participants provided optional blood and urine samples which will be used to determine whether the study agents significantly change biomarkers and other risk factors related to cardiovascular disease and cancer Selected participants either have specimens collected through mailed specimen collection kits that are returned by the participant or have blood urine blood pressure and anthropometric measurements collected by technicians from Examination Management Services Inc EMSI a national clinical services provider A subgroup of those who provide baseline specimens and measurements are asked to provide follow-up samples and measurements
At baseline and year 2 of the trial approximately 600 participants living within driving distance of Boston Massachusetts provide additional measurements from in-clinic study visits at the Clinical and Translational Science Center CTSC of Brigham and Womens Hospital These visits include cognitive function assessments anthropometrics physical function assessments blood pressure and other measurements The trial will assess whether the study agents significantly affect changes in these variables over time
Primary Hypotheses
1 A cocoa extract supplement will reduce the risk of major cardiovascular events defined as a composite endpoint of myocardial infarction stroke cardiovascular mortality coronary revascularization unstable angina or ACS requiring hospitalization carotid artery surgery and peripheral artery surgery or angioplasty
2 A daily multivitamin will reduce the risk of invasive cancer excluding non-melanoma skin cancer
Secondary Hypotheses
1 Cocoa extract will reduce the risk of a composite endpoint of MI stroke cardiovascular mortality and coronary revascularization
2 Cocoa extract will reduce the risk of invasive cancer excluding non-melanoma skin cancer
3 A daily multivitamin will reduce the risk of major cardiovascular events
4 Cocoa extract andor a daily multivitamin will reduce the combined endpoint of major cardiovascular events plus all-cause mortality
5 Cocoa extract andor a daily multivitamin will reduce the risk of individual cardiovascular events including myocardial infarction stroke cardiovascular mortality coronary revascularization unstable angina or ACS requiring hospitalization carotid artery surgery and peripheral artery surgery or angioplasty and total mortality plus site-specific cancers including breast colorectal and lung cancer
6 A daily multivitamin will reduce the risk of cancer among women and men with a history of cancer at baseline
7 In a subset of equal numbers of female and male COSMOS respondents who provide baseline bloods andor urine samples cocoa extract andor a daily multivitamin will significantly change blood andor urinary levels of flavonoids or their metabolites from baseline to 1 2 or 3 years of follow-up
Tertiary Aim
To assess whether the cocoa extract andor a daily multivitamin exhibit synergistic effects on risk of major cardiovascular events or cancer and if the effects vary by nutritional status or medication use
Aims of Clinical and Translational Science Center CTSC Component
To test whether the cocoa extract andor a daily multivitamin has beneficial effects on
1 Systolic and diastolic blood pressure
2 Pulse wave velocity PWV and central blood pressure indices as measured by pulse wave analysis
3 Cognitive function and memory
4 Physical performance as assessed by balance tests grip strength timed chair stands and walking speed
5 Bone loss in the spine hip and total body as assessed by bone-mineral density BMD and changes in body composition as assessed by dual x-ray absorpiometry DXA
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None