Q. COSMOS participants are not allowed to take (a) nonstudy vitamin D supplements of more than 1000 international units (IU) per day, or (b) calcium supplements of more than 1200 mg per day. What are the reasons for these restrictions?
Q. What is the COSMOS study?
A. The term COSMOS is derived from “COcoa Supplement and Multivitamin Outcomes Study.” The COSMOS Study is a large-scale, placebo-controlled, clinical trial testing the risks and benefits of supplemental cocoa extract and a multivitamin in the primary prevention of cancer and cardiovascular disease. The primary outcomes of the study are heart attack, stroke, coronary revascularization, cancer and death.
Q. Who is running the COSMOS study?
A. The study is being run by Brigham and Women’s Hospital, an affiliate of Harvard Medical School, in Boston, MA, and the Fred Hutchinson Cancer Research Center in Seattle, WA. Funding for COSMOS is from Mars Symbioscience and Pfizer Inc, along with support for ancillary studies from the National Institutes of Health.
Q. Who is participating in the COSMOS study?
A. Women aged 65 or older and men aged 60 or older who have not previously had a heart attack or stroke, or cancer (other than skin cancer) diagnosed within the last two years are participating in the COSMOS study. Participants live in every state in the country and receive all of the study materials (study pills and study forms) via postal mail.
Q. What does participation involve?
A. Interested individuals first complete questionnaires that will help us determine if they are eligible to participate, along with an informed consent form. If an individual is eligible for COSMOS, we will assign her or him 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. A placebo looks exactly like the study supplement, but it contains no active ingredients. A study participant has an equal chance of being assigned to any of these four groups and, thus, a three out of four chance of receiving at least one of the active interventions being tested.
No matter which group a participant is assigned to, she or he will take three pills each day – two capsules that contain either cocoa extract or cocoa extract placebo, and one tablet that contains either a multivitamin or multivitamin placebo. Participants receive their study pills in convenient calendar packages via postal mail.
Each year that a participant is in the research study, she or he will receive a mailed questionnaire that takes approximately 15-20 minutes to complete. The form will contain questions about health; lifestyle habits such as exercise, diet, and smoking; use of medications and dietary supplements; and family history of illness. Occasionally, participants will be contacted by phone to collect information or to clarify questionnaire responses.
During the study, participants must agree to:
• avoid taking multivitamin supplements
• limit their total intake of vitamin D (besides the study medication) from supplements to 1000 IU or less per day
• limit their total intake of calcium from supplements to 1200 mg or less per day
Q. Can I get the same cocoa flavanols from chocolate?
A. It would be very difficult to get this amount of cocoa flavanols from chocolate without adding a large number of calories. See the chart below.
Q. Will my health information be kept confidential?
A. Yes! We are committed to protecting your privacy. Information from completed questionnaires and medical records is identified in our computer files by study number only, and only a few staff members, who have received training in—and understand the importance of—protecting confidential health information, have access to the file that links study numbers with participants’ names. Your information will be used only for COSMOS, and no personal information will identify participants in published research findings. Your trust is essential to the success of the study, and we would never do anything to risk losing your faith in us.
Q. What is the reason for collecting blood and urine samples from study participants?
A. As an optional part of COSMOS, we are requesting blood and urine samples from willing participants selected at the start of the study. These samples will allow us to study whether baseline blood levels of cocoa flavanols, other pertinent nutritional biomarkers (chemicals), and vascular/metabolic biomarkers are related to (a) an individual’s risk for developing a particular disease and (b) the effects of cocoa extract or multivitamin supplements on pathways relevant to major health conditions. Study participants will receive a blood and urine kit, including collection instructions, in the postal mail. We know that some participants will be able to have their blood drawn by their local healthcare providers, whereas others will require assistance in locating someone to draw their blood. If you receive a blood kit and need assistance in arranging the blood draw, please call us at 1-800-633-6913.
Q. May I have a copy of my blood test results? If not, why?
A. Unfortunately, we do not release the results of blood tests to study participants. There are four reasons for this policy. First, we will not analyze the blood samples until the end of the study (several years from now), so the results will not be an accurate measure of flavonoids and other biomarker levels at that time. Second, some lab tests will be done on only a sample of participants (not on everyone). Third, the labs we will use to analyze the blood samples are certified as research labs rather than clinical labs—this means that they apply different standards for analysis and their results cannot be directly compared with results from clinical labs. Fourth, informing participants of blood test results could bias the study’s findings if a large percentage of participants start to take cocoa flavanol supplements on their own to achieve a blood level that they think is best (COSMOS is designed to test this very question—i.e., does a higher blood level of flavonoids actually provide health benefits compared with an “average” blood level?).
Q. COSMOS participants are not allowed to take (a) nonstudy vitamin D supplements totalling more than 1000 international units (IU) per day, or (b) calcium supplements totalling more than 1200 mg per day. What are the reasons for these restrictions?
A. These restrictions are in place so that the COSMOS study will be able to clearly determine whether the cocoa extract and multivitamin supplements prevent heart attack, stroke, and cancer while also ensuring the safety of participants, whether they are assigned to take placebo or study multivitamin pills containing 1000 IU/day vitamin D and 220 mg/day calcium. People who take large amounts of supplemental vitamin D or calcium outside the study will weaken the study’s ability to detect benefits for these nutrients, should such benefits exist. Moreover, the risks of consuming high doses of supplemental vitamin D (more than 4000 IU/day) on a long-term basis are not completely known. In addition, large amounts of supplemental calcium (above the amount we allow) may combine with even modest amounts of supplemental vitamin D to increase the risk for kidney stones.
Please note that COSMOS participants are allowed to take up to 1000 IU/day of vitamin D in nonstudy supplements should they choose to do so. Together with intake from food (which averages 200-300 IU/day), most participants can opt to consume at least 1200 IU/day of vitamin D on their own, which is actually more than the “recommended dietary allowances” (RDA) of 600 IU/day for adults up to age 70 and 800 IU/day for those aged 71 and older recently set by the Institute of Medicine (IOM). Thus, no one will become vitamin D deficient due to participation in COSMOS, even if assigned to the placebo group. Moreover, no participant assigned to take vitamin D will get too much unless a nonstudy supplement containing more than the 1000 IU/day allowed is also taken. In other words, participants in the multivitamin group who follow the study requirements will be consuming at most about 2200 IU/day of vitamin D, which is below the safety limit of 4000 IU/day set by the IOM. Thus, neither group should have safety concerns from participation.
COSMOS participants are also allowed to take up to 1200 mg/day of calcium in supplements should they choose to do so. Together with intake from food (which averages about 700 mg/day), most participants can opt to consume almost 2000 mg/day. This is not only higher than the current RDA for calcium—1000 mg/day for men aged 51-70 and 1200 mg/day for women aged 51-70 and adults aged 71 and older—but is also close to the IOM’s safety limit of 2000 mg/day. No one will become calcium deficient as a result of participating in COSMOS.
Q. What should I do if I forget to take my study pills?
A. If you realize before you go to bed that you forgot to take that day’s pills, please take them then. However, if you accidentally skip a day, do not “double up” on the pills the next day—just resume taking your pills according to schedule and leave the unused ones in the calendar pack.
Q. Should I take my study pills with food?
A. To aid absorption, it is best to take the pills with a meal or snack. However, it is acceptable to take them on an empty stomach if it is easier to remember to take your pills at other times of the day.
Q. I’ve recently moved into a new home. How can I ensure that I will continue to receive my study pills and questionnaires in a timely fashion?
A. To ensure that study mailings continue without delay, please notify us of changes in your mailing address, phone number, and e-mail as soon as possible (1-800-633-6913 or firstname.lastname@example.org).
Q. The main goal of COSMOS is to determine whether cocoa extract or a multivitamin can reduce the risk of cancer, heart disease, and stroke. Will COSMOS examine other health outcomes as well?
A. Yes! We will be conducting ancillary studies in COSMOS to assess whether cocoa flavanols or multivitamin supplements confer other health benefits, such as lowering the risk for:
• Cognitive decline
If your early questionnaire responses indicated that you were eligible for one or more of these ancillary (add-on) investigations, you may have received separate mailings about these optional studies and may now be participating in them. In addition, participants who live within driving distance of Brigham and Women’s Hospital in Boston, Massachusetts have been invited for optional clinic visits to have more detailed studies, including tests of blood sugar, cognitive and physical function, and blood pressure.
Q. Why do you ask for date of birth on every questionnaire?
A. In a study as large as COSMOS, there are often one or more participants with the same name. In addition to your name and study ID number, your date of birth serves as a unique identifier.
Q. Why do you ask for the name and telephone number of a contact person?
A. In a long-term study such as COSMOS, we occasionally lose touch with study participants when they move or have other changes in their status. We will write or telephone your contact person to ask for your current address or phone number only if we cannot reach you after multiple attempts.
Q. My doctor wants to know what study pills I am taking as part of COSMOS. What should I tell them?
A. Please tell your doctor that you are taking part in a 4-year randomized clinical trial of cocoa extract (containing 600 mg per day of cocoa flavanols) and a multivitamin for the prevention of cardiovascular disease and cancer. Your orange study capsules contain either 600 mg of cocoa extract or placebo, and your grey study tablet contains either a multivitamin or placebo. At the end of the trial, you will be told which type of study capsules you were taking. Although it may be helpful for your doctor to be aware of your participation in COSMOS, neither you nor your doctor should assume that the study capsules can replace any of your prescribed medications.