COcoa Supplement and Multivitamin Outcomes Study
Kľúčové slová
Abstrakt
Popis
The COcoa Supplement and Multivitamin Outcomes Study (COSMOS) is a randomized clinical trial of cocoa extract supplement (containing a total of 600 mg/d 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.
Participants in COSMOS were recruited from among Women's 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 ResearchMatch.org, 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 U.S. 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.
At baseline, approximately 7,000 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 after each year of follow-up, approximately 4,000 COSMOS participants complete web-based assessments of cognitive function. During the trial, participants will complete up to 4 assessments, each of which takes approximately 25 minutes to complete. The trial will assess whether the study agents significantly affect change in cognitive function over time.
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 Women's 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, and coronary revascularization;
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 invasive cancer (excluding non-melanoma skin cancer);
2. A daily multivitamin will reduce the risk of major cardiovascular events;
3. Cocoa extract and/or a daily multivitamin will reduce the combined endpoint of major cardiovascular events plus all-cause mortality;
4. Cocoa extract and/or a daily multivitamin will reduce the risk of individual cardiovascular events, including myocardial infarction, stroke, cardiovascular mortality, coronary revascularization, and total mortality; plus site-specific cancers, including breast, colorectal, and lung cancer;
5. A daily multivitamin will reduce the risk of cancer among women and men with a history of cancer at baseline;
6. In a subset of equal numbers of female and male COSMOS respondents who provide baseline bloods, cocoa extract and/or a daily multivitamin will significantly change levels of blood flavonoids from baseline to 2 years of follow-up.
Tertiary Aim:
To assess whether the cocoa extract and/or 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 and/or 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);
6. Metabolic and functional changes within the hippocampus using cerebral blood volume (CBV) MRI.
Termíny
| Naposledy overené: | 06/30/2020 |
| Prvý príspevok: | 04/16/2015 |
| Odhadovaná registrácia bola odoslaná: | 04/16/2015 |
| Prvý príspevok: | 04/20/2015 |
| Posledná aktualizácia bola odoslaná: | 07/12/2020 |
| Posledná aktualizácia bola zverejnená: | 07/14/2020 |
| Aktuálny dátum začatia štúdie: | 05/31/2015 |
| Odhadovaný dátum dokončenia primárneho okruhu: | 10/31/2021 |
| Odhadovaný dátum dokončenia štúdie: | 10/31/2021 |
Stav alebo choroba
Intervencia / liečba
Dietary Supplement: Cocoa extract
Dietary Supplement: Multivitamin
Dietary Supplement: Cocoa extract placebo
Dietary Supplement: Multivitamin placebo
Fáza
Skupiny zbraní
| Arm | Intervencia / liečba |
|---|---|
| Active Comparator: Cocoa extract + multivitamin | |
| Active Comparator: Cocoa extract + multivitamin placebo | |
| Active Comparator: Cocoa extract placebo + multivitamin | |
| Placebo Comparator: Cocoa extract placebo + multivitamin placebo |
Kritériá oprávnenosti
| Vek vhodný na štúdium | 60 Years To 60 Years |
| Pohlavia vhodné na štúdium | All |
| Prijíma zdravých dobrovoľníkov | Áno |
| Kritériá | Inclusion Criteria: 1. Women ≥ 65 years of age participating in the Women's Health Initiative (WHI) Extension Study. 2. Men ≥ 60 years of age and women age ≥ 65 years of age who were contacted for but not randomized into the VITAL trial. 3. Other women ≥ 65 years of age and men aged ≥ 60 years of age who responded to targeted mass mailings and volunteers who learned about the trial through the media or through ResearchMatch.org, an electronic recruitment website. 4. Willing to participate, as evidenced by providing informed consent and completing all required baseline forms. Exclusion Criteria: 1. History of myocardial infarction or stroke. 2. Diagnosed with invasive cancer other than non-melanoma skin cancer in the last 2 years prior to enrollment. 3. Any serious illness that would preclude participation and/or completion of the trial, including the diagnosis of kidney failure and current dialysis treatment. 4. Taking cocoa extract or multivitamin supplements and not willing to forego use during the trial. 5. Taking total supplemental vitamin D > 1,000 IU/day and not willing to forego use during the trial. 6. Taking total supplemental calcium > 1,200 mg/day and not willing to forego use during the trial. 7. Extreme sensitivity to caffeine. 8. Consume < 75% of the expected number of both types of supplements during the run-in phase. 9. Unable to communicate in English due to language barrier or mental incapacity. |
Výsledok
Primárne výstupné opatrenia
1. Cardiovascular disease (CVD) events [5 years]
2. Invasive cancer [5 years]
Opatrenia sekundárnych výsledkov
1. Combined endpoint of major cardiovascular events plus all-cause mortality [5 years]
2. Myocardial infarction [5 years]
3. Stroke [5 years]
4. Cardiovascular mortality [5 years]
5. Coronary revascularization [5 years]
6. Total mortality [5 years]
7. Breast cancer [5 years]
8. Colorectal cancer [5 years]
9. Lung cancer [5 years]
10. Blood flavonoid levels [2 years]
Ostatné výstupné opatrenia
1. Cognitive function [2-5 years]
2. Systolic and diastolic blood pressure [2 years]
3. Pulse wave velocity and central blood pressure indices [2 years]
4. Physical performance [2 years]
5. Bone mass density in hip, spine, and total body, and body composition [2 years]
6. Body composition [2 years]
7. Metabolic and functional change within hippocampus [2 years]
