Seeking participants for a healthier future
Written by Jessica Binkley Lain
Investigators are working to eliminate the barriers of recruiting older adults for clinical research to increase the pipeline of anti-aging interventions.
The primary health challenges that emerge with aging, such as preventing dementia, cancer and heart disease, remain unsolved. Often, the only way to solve these is by testing new anti-aging compounds in volunteers.
Clinical trials are only as good as their participants, and when it comes to studying an aging population, there are many challenges to recruit and retain study participants.
“Clinical research into aging at UT Health Science Center San Antonio is moving science forward,” said Kimberly Summers, PharmD, associate vice president for research operations. “The more we understand about the interactions between genetic, behavioral, social and environmental factors involved in the aging process, the closer we get to early interventions that prevent age-related diseases and degenerative decline.”
UT Health Science Center San Antonio conducts around 40 active clinical studies focused on aging research, Summers said. Approximately 20% of those active studies are interventional, where a new drug is tested, and the remaining are longitudinal studies that follow subjects in real time to gain insight into cause-and-effect relationships for aging, she said.
Summers explained that the major barriers to the recruitment of older participants include substantial health issues that could exclude them from the trial, social and cultural barriers, and occasionally an impaired capacity to provide effective informed consent.
“Our investigators and study staff have expertise that goes beyond the informed consent document and often engages family members and caretakers as part of the process,” Summers said, adding that flexibility in time and location of visits and the use of virtual visits are offered to increase the ability of the elderly to participate in a trial.
Accounting for comorbidities
Another major challenge facing clinical research on aging is when the study calls for healthy older adults as participants. Older patients often have other diseases in addition to the one being studied, which can complicate the study and may prevent participation.
“It’s tough because we want to control as many variables as possible. If a study is testing a drug for diabetes, you want your participant to have diabetes, but then you want any other comorbidities to be stable or controlled so you can see the effects of the intervention,” said Tiffany Cortes, MD, assistant professor of medicine in the Division of Endocrinology, Metabolism and Diabetes and researcher at the university’s Sam and Ann Barshop Institute for Longevity and Aging Studies. “But the challenge in targeting older populations is, as you get older, you’re more likely to have many other comorbidities. Trying to get somebody who is 75 without cardiovascular or metabolic disease, for example, can be very difficult.”
Cortes leads an ongoing clinical trial studying the effect of GLP-1 receptor agonists like semaglutide on physical strength, body fat versus muscle composition, and biomarkers of aging in older adults with prediabetes or diabetes.
“When a study is seeking ‘healthier older adults,’ that often means the exclusion of a lot of people who would probably have the most to benefit,” Cortes said.
Cortes studies the effects of semaglutide — a U.S. Food and Drug Administration-approved medication commonly prescribed for Type 2 diabetes and weight management — on the body composition in adults 65 and older, analyzing measures of lean body mass, fat mass and changes in physical activity. Cortes is also examining changes on the cellular level, looking for biomarkers of aging, such as signs of inflammation and cellular senescence.
“Looking at both the physical function and cellular level changes together, we can determine if semaglutide has not only glycemic and weight-control benefits, but also aging-focused benefits for older adults,” Cortes said. She also explained that there are some concerns to consider for this older age group about retaining muscle mass while taking a drug that aids in weight loss, because some of this weight loss may come from muscle. All participants in the study are provided lifestyle counseling with expert dietitians and exercise physiologists.
Reciprocal research
“Something I love about doing this research is the impact of our studies on our participants,” Cortes said. “I get to see the joy our patients have in being able to give back to their community and advance scientific knowledge. Frequently they are eager to learn about other trials and ways they can contribute.”
When participants can become active again in their community, it garners not only interest in a study, but also more trust in science and medicine, she explained. It’s also important for researchers to give back to the participants who are in aging studies that do not test an intervention against aging, but rather, where the natural history of aging itself is followed.
“It should be a reciprocal interaction. It’s important to offer them something meaningful,” said Claudia Satizabal, PhD, associate professor in the Department of Population Health Sciences and investigator at the Glenn Biggs Institute for Alzheimer’s and Neurodegenerative Diseases at UT Health Science Center San Antonio.
Satizabal leads the San Antonio Heart and Mind Study, a longitudinal study that revisits the San Antonio Heart Study, conducted at the university between 1979 and 2006. For this current study, which was awarded a five-year, $15.5 million grant from the National Institute on Aging, Satizabal is investigating why older Mexican Americans in the San Antonio region experience a higher rate of dementia than older non-Hispanic white adults.
While the original study focused on diabetes and heart disease in participants between 25 and 64 years old, the new study will utilize MRI and positron emission tomography to measure amyloid and tau buildup in the brains of those same participants, who are now in their 60s and older.
Beyond monetary compensation, Satizabal emphasizes the importance of providing education and meaning for participants, especially in older and underrepresented populations.
Building community connection and trust
Population Health Sciences and investigator at the Biggs Institute
“We need to go into the community to explain why research is important and take the time to really establish that connection,” Satizabal said. “It takes time to do this, but it has a high payoff because once you establish that relationship with the community, they know they’re contributing to something that is beneficial for everyone, and you also are able understand their concerns.”
This is especially important for observational studies, such as the Heart and Mind Study, in which participants aren’t given an opportunity to try a new drug or treatment as an incentive.
“It’s important to explain how their contributions matter and are helping to shape research and health policy. Because without the participants, we wouldn’t be able to do what we do,” Satizabal said.
In addition, participants in Satizabal’s study are informed of their lab results and any findings pertaining to their personal health, she said. This provides a free, complete health checkup regularly, to which some study participants may not have access. Medical concerns are discussed with primary care providers, and recommendations or referrals for further care or counseling are also offered. In addition, all study materials are offered in English and Spanish to be as inclusive as possible. Transportation services and caregiving programs are also provided for participants who need them.
“We’re trying to be as comprehensive as possible to have a system that accommodates all types of situations so that the participant is not burdened by their involvement in the study,” she said.
Ultimately, understanding the community, building trust and establishing a partnership with enrolled participants is crucial to recruiting and retaining older participants. Thus, the aging research teams at UT Health Science Center San Antonio often partner with local churches, gyms, nursing homes, rehabilitation centers, libraries and recreation centers to identify older study participants. Past study participants are also often the best recruiters of new study recruits, which underscores the importance of establishing trust within the local community.
With well-informed, enthusiastic study participants, investigators at UT Health Science Center San Antonio will continue to make clinical discoveries that prevent physiological and cognitive degeneration and chronic illness in aging populations in South Texas and far beyond.
Multi-omic approaches to understanding aging
While the health effects of regular exercise are well understood, its impact at the genetic and molecular level is not. These unresolved questions drove UT Health Science Center San Antonio researchers to co-lead the National Institutes of Health clinical exercise trial called MoTrPAC.
The Molecular Transducers of Physical Activity Consortium is a far-reaching clinical trial that brings together a collaborative national network of researchers from an array of scientific disciplines. MoTrPAC attempts to determine the molecular mechanisms underlying the effects of physical activity on the human body. Data integration and sharing allows researchers to gain insights into how various molecular components interact and influence each other in complex biological systems. A multi-omics study design gives investigators a more complete understanding of biological processes by analyzing multiple omics datasets simultaneously.
“For the past seven years, I have been one of the principal investigators for the largest investment the NIH has made on the role of exercise in human health,” said Blake B. Rasmussen, PhD, director of the Center for Metabolic Health at UT Health Science Center San Antonio. “It combines transcriptomics, proteomics, metabolomics, lipidomics from blood and tissues collected from humans before and after three months of exercise training.”
Rasmussen believes MoTrPAC’s multi-omics approach will yield many answers to important metabolic questions.
Why is it so hard to gain muscle as you age?
The MoTrPAC team at UT Health Science Center San Antonio has demonstrated that it is more difficult to maintain muscle mass with age, let alone increase muscle mass. Data from younger and older adults who completed a three-month weight training program showed that younger adults put on about 7–8 pounds of muscle after three months, compared to 1–2 pounds for older participants, Rasmussen said.
“Older adults don’t respond as well to nutrition or exercise as compared to younger adults,” he said. “Nutrition and exercise are key components to maintaining muscle function and size. As we age, older adults tend to have a little bit more difficulty in using the anabolic components of nutrition, such as protein, to help build and restore their muscles.”
By using genomics, transcriptomics, proteomics, metabolomics and epigenomics, the MoTrPAC clinical trial is designed for further discovery on why older adults cannot use protein to build muscle as well as younger adults. Investigators are currently developing novel nutritional, small molecule, mechanical and exercise therapies to help older adults maintain their muscle function into advanced age, Rasmussen said.
Senescent cells in the muscles of older adults may decrease the ability to use protein to build muscle after exercise. Thus, small molecular senolytic drugs targeting muscle senescent cells are being tested to assess whether they help older adults gain more muscle after exercise.
Essential biomarkers
As the MoTrPAC trial studies the molecular responses to exercise, it will identify biomarkers that could provide indicators of an individual’s response to exercise, leading to personalized exercise recommendations and improved health outcomes for older adults.
“We may learn what types of exercises are the best for older adults,” Rasmussen said. “We may learn how much rest is required between exercise bouts when trying to improve muscle size and function. We may discover what foods should be prescribed for older adults. We may identify particular pathways at the molecular level that may lead to the discovery of new drugs or nutraceuticals.”
The MoTrPAC clinical trial, combined with this breadth of established metabolic scholarship, is poised to lead discovery on the mechanisms of aging — research that could yield new strategies for disease prevention and treatment and life-changing therapies for older adults.
Learn more about clinical trials
Barshop Institute: Want to be a part of advancing medical knowledge to treat or prevent various age-related diseases? Click here to learn about current clinical trials at the Barshop Institute.
Biggs Institute: Want to improve scientific understanding of brain aging and help discover new drugs and treatments for dementia? Click here to find current clinical trials at the Biggs Institute.
