My Experience on a Clinical Research Trial

Neither rain nor snow nor extreme heat or cold or upset stomach prevented me from taking three pills a day, without fail, during the over two years I participated in a clinical research trial. I never missed a day, not one.

Credit: Getty

From 2019 until the end of 2021, the pills I was taking were part of the COSMOS ­— Cocoa Supplement and Multivitamin Outcomes Study — that explored whether cocoa extract and multivitamins reduced the risk of heart disease, stroke and cancer, three of the deadliest killers. The trial was conducted by Brigham and Women's Hospital in Boston with key collaboration and support from the Fred Hutchinson Cancer Research Center in Seattle.

I opted to participate because I wanted to contribute to science and knowledge. Since I wasn't compensated, it felt good to contribute to research that aimed to diminish the effects of these deadly diseases.

I was one of 21,442 participants in this research study comprised of women over age 65 and men over 60. The specific pills taken during the trial were a multivitamin Centrum Silver and a cocoa flavanol (a type of plant nutrient) product called Cocoa Via.

The study was referred to as a double-blind test because no one knew who was taking the actual pills and placebos, and that ensures there's no bias of the people conducting the test.

Since I learned when the results were announced that I was taking the actual flavanol pills, and not the placebos, did I reap any special benefits? 

Howard Sesso, an associate epidemiologist with the Division of Preventive Medicine at Brigham and Women's Hospital in Boston, who co-led the study, is positive but muted about the results of participants like myself. 

"For those taking cocoa flavanols, the promising signals for cardiovascular disease prevention suggests that they may have benefited," Sesso said. "However, those in both the active and placebo cocoa flavanol groups still developed cardiovascular disease."

During the trial, 410 out of 10,710 participants taking cocoa extract, and 456 out of 10,723 participants taking a placebo, had confirmed cardiovascular events, including heart attacks, strokes, unstable angina requiring hospitalization and death causes by cardiovascular disease. This part of the study resulted in a modest 10% reduction in cardiovascular events for those taking cocoa extract. Sesso added that of the people who continued taking the pills on a sustaining basis, the results were closer to 15% that had fewer cardiovascular problems.

"So if a million people, for example, develop cardiovascular problems, that eliminates problems in one-hundred fifty thousand of them, and that's substantial," Sesso said.

Garnet Anderson, director of Public Health Sciences Division at the Fred Hutchinson Cancer Research Center, explained that "we saw no statistically significant reduction in cardiovascular disease with cocoa flavanol supplement, although there was some supportive data to suggest a possible benefit." 

Statistically, she said, "We don't know if the ten percent reduction is real or a chance variation for no difference." To be more effective, the trial would have needed to engage more participants over a longer period and those studies are hard to pull off and fund.

Older adults were targeted because, Sesso noted, "as we get older, the risks of cardiovascular diseases go up. Had we recruited younger individuals, their rates of cardiovascular diseases would be lower and we'd need to recruit more people."

Of course, the volunteers who were ingesting placebos were crucial to the trial. 

"It allows us to directly compare these two groups for their likelihood of developing the outcomes of interest in COSMOS," said Sesso. "For cocoa flavanols, it was cardiovascular disease and its individual components; for a multivitamin, it was total invasive cancer."

Participants were identified in three major ways: 1) women from the Women's Health Initiative who had participated in a large post-menopausal study, mostly at the Fred Hutchinson Cancer Research Center, 2) Brigham and Women's Hospital's pool of candidates who had participated in large trials of vitamin supplements and aspirins and 3) mass mailings that got the word out.

According to Sesso, identifying over 20,000 people willing to get involved is a gargantuan task that requires enormous persistence.

During the test, participants filled out questionnaires every six months. "Overall there were few side effects and the pills were well tolerated," Sesso said.

The results of the tests revealed that "While neither supplement significantly reduced the primary outcome of cardiovascular event, people randomized to receive the cocoa flavanol supplement had a twenty-seven percent lower rate of cardiovascular death," he said.  

JoAnn Manson of the Division of Preventive Medicine at Brigham and Women's Hospital, who co-led the trial, noted that the results indicated the positive effects of taking flavanols, which are found in cocoa, tea, grapes and berries.

The result discovered that participants taking cocoa extract reduced death by cardiovascular disease by 27%, but the extract didn't reduce other individual cardiovascular outcomes or curtail the chances of death by cancer. The multivitamin reduced the chances of lung cancer by 38% compared with the placebo, but had no significant effect on reducing breast cancer, colorectal cancer, prostate cancer or melanoma.

Both Sesso and Manson generated the idea for the study, and wanted it to be a collaboration among academia, industry and government. The National Institutes of Health (NIH) supported some ancillary cognitive studies, and funding from Mars Edge and Pfizer Consumer Health helped support it, but they had no bearing on the results.

Sesso praised the participants who volunteered. Some were involved for three to four years, which requires an enormous commitment and dedication.

"The people involved understood the importance of research like that. It takes a special person that is willing and able to participate," he said.

Said Anderson, "There are some people who don't feel as if they can donate money, but participating is another way of contributing."

Interviewed for a COSMOS newsletter, participants had a wide range of motivations for getting involved.

Marcia of Indiana lost her husband to cancer and wanted to "fight back and be a part of the study." Robert of Pennsylvania said, "How often does an opportunity to contribute, to make a difference, fall in your lap? And what have I got to lose?" And Ora of Texas, who is African American, said Blacks are often underrepresented in these studies, which convinced her to participate.

When asked why the study focuses on pills instead of diets, Anderson said, "Americans want simple, easy fixes and want a silver bullet. We believe nutrition is important, but not always captured in a capsule." 

Eliciting a more detailed answer would analyze "the way we eat, and that's much more complicated and more expensive," she added.

Bottom line, Sesso said, the study "saw some promising signals for cardiovascular results that we need to learn more about regarding cocoa flavanols." 

For example, he explained, we need to learn more about the exact portions of ingredients that can reduce heart problems. Is it 500 milligrams or two pills a day?  Would you reap larger benefits if you ingested three pills a day?

"A good trial answers many questions and asks even more," Sesso said. "We're eager now to dive into understanding more about the cardiovascular mechanism that underlies the effect and dig deeper into COSMOS. We're thinking carefully whether a second trial is warranted and what would this new trial consist of."

And according to Sesso, the results suggest that people might consider adding tea, berries, cocoa and grapes to their diets to reduce the chances of cardiovascular diseases, as well as vegetables, lean meats and other protein sources and limited sugar.

"We know how to reduce one's risk of cardiovascular diseases through increased physical activity, reduced body weight, and monitoring blood pressure, among other things," he said.