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NIH-funded study to recruit thousands of participants to reveal exercise impact at the molecular level

Rachel Britt, CFComms@od.nih.gov

Melissa McGowan, mcgowann@mail.nih.gov

NIA Press Office, NIAPressTeam@mail.nih.gov

In the largest exercise research program of its kind, researchers are poised to collect and turn data from nearly 2,600 volunteers into comprehensive maps of the molecular changes in the body due to exercise. It is well known that physical activity has substantial health benefits, but we do not fully understand why, especially at the molecular level. The National Institutes of Health-funded Molecular Transducers of Physical Activity Consortium (MoTrPAC) aims to increase our understanding by measuring molecular changes in healthy adults and children before, during, and after exercise. The large study size is meant to account for person-to-person variation, and to reveal differences based on demographics like age, race, and gender. MoTrPAC researchers published a paper detailing their approach to this ambitious research project. They are currently reviewing lessons from an initial phase with a smaller group of adult volunteers and multiple rounds of preclinical animal model studies to optimize their protocols and prepare to scale-up for full recruitment.

“MoTrPAC was launched to fill an important gap in exercise research,” said NIH Director Francis S. Collins, M.D., Ph.D. “It shifts focus from a specific organ or disease, to a fundamental understanding of exercise at the molecular level — an understanding that may lead to personalized, prescribed exercise regimens based on an individual’s needs and traits.”

The MoTrPAC clinical study pairs methods well-established in exercise research with unique study aspects to move our fundamental understanding of exercise forward. One of the most distinctive study features is its size. MoTrPAC set the ambitious goal amongst its 11 clinical sites to recruit about 2,600 healthy volunteers across a wide age range (10 to 60-plus years old) and with balanced participation by the sexes. Part of the study will test how the response to exercise changes after generally inactive participants complete a 12-week supervised exercise regimen. Sedentary adults will be randomly assigned to an endurance training regimen (treadmill, cycling), a resistance training regimen (weightlifting), or an inactive control group. Low-activity children will be randomly assigned to an endurance training regimen, or to a control group where they pursue their normal activities. Contributing to the overall size of the study is a separate group of highly-active adults and youths who will help researchers understand what exercise looks like at the molecular level in those who have exercised vigorously and consistently over an extended period.

Another unique facet of MoTrPAC is that volunteers provide samples — or biospecimens — before, during, and after exercise that will go through a complex array of molecular assays. Adults provide blood, fat, and muscle tissues, while children provide only blood samples. MoTrPAC researchers implemented an early study phase with a limited number of adult volunteers that is meant to ensure the complex study design is feasible both for the researchers and the participants before scaling up. The researchers and their data and safety monitoring board are reviewing lessons learned, so that recruitment may continue under optimized protocols. Recruitment currently is on-hold due to safety concerns over COVID-19, and will resume when it is safe to do so. To see if a MoTrPAC clinical center will be recruiting near you, visit https://motrpac.org/join/volunteerHome.cfm.

Preclinical studies in an animal model also set the stage for full-scale MoTrPAC clinical studies and enabled MoTrPAC to generate data from tissues that cannot be collected from humans, expanding the scope of the consortium. Researchers at three preclinical animal study sites conducted both a single round of exercise and an exercise training regimen in young and aged rats. Following the exercise round, or after training, 19 biospecimens were collected per animal. The number of biospecimens per animal is a powerful aspect of MoTrPAC, as it gives a nearly whole-body look at the effects of exercise, which has never been done before. The biospecimens collected from the preclinical studies were sent to MoTrPAC’s biorepository, managed by the consortium’s coordinating center. The biospecimens also provided raw material for the nine chemical analysis sites to generate data on exercise-responsive biomolecules like genes, indicators of gene activity, proteins, molecules involved in metabolism, and molecular signals in cell-to-cell communication.

Some data from the preclinical studies is available through the MoTrPAC Data Hub, and more is expected soon. MoTrPAC’s bioinformatics center is charged with data quality control, bioinformatics analysis, and making the data available through the data hub. MoTrPAC researchers alone cannot answer all our questions about the molecular basis of the health benefits of exercise. Making the data widely available brings new perspectives to the topic than would be otherwise possible. They may discover how exercise affects so many aspects of health throughout the body like metabolism, immune responses, and cardiovascular function.

Ultimately, MoTrPAC aims to have a positive impact on human health. The study and resulting data integration are an immense undertaking, and provide an unprecedented opportunity to explore the molecular basis for the benefits of exercise. The information MoTrPAC assembles about endurance and resistance exercise in a wide range of individuals and in different tissues may influence exercise guidelines, making them more tailored for specific groups of people. One day, a doctor may be able to prescribe a personalized exercise routine based on what is likely to create the best outcome for an individual. Other researchers may use the data to identify drugs that mimic the molecular signals of exercise, so-called exercise-mimetics, which could help people who are unable to exercise.

MoTrPAC is funded by the NIH Common Fund and overseen in collaboration with the National Institute on Aging, the National Institute of Arthritis and Musculoskeletal and Skin Diseases, and the National Institute of Diabetes and Digestive and Kidney Diseases. A list of funded MoTrPAC projects is at https://motrpac.org/aboutUs.cfm. MoTrPAC’s adult and pediatric clinical studies are registered with clinicaltrials.gov under NCT03960827 and NCT04151199, respectively.

Flow chart that uses colored boxes in a vertical row to show the steps in gathering the information for the study and how that data moves through a process for analysis. Between each box is an arrow showing the flow of information. On the right of the flow chart is a list of biospecimens and on the left is a box labeled ancillary studies. See caption below for general information.
Image Credit: Jill K Gregory, ©Mount Sinai Health System

General overview of MoTrPAC. Preclinical animal study sites and human clinical exercise sites will collect biospecimen samples. The samples go to a central biorepository and then be distributed to chemical analysis sites. A portion of the biospecimen samples will be kept at the biorepository for future ancillary study opportunities by the scientific community. Data generated by the chemical analysis sites will be transferred to the bioinformatics center for integration of the data with the goal of generating a molecular map of exercise. The data will be available to the scientific community via the MoTrPAC Data Hub.

About the National Institute on Aging: The NIA leads the federal government effort conducting and supporting research on aging and the health and well-being of older people. It provides information on age-related cognitive change and neurodegenerative disease specifically at its Alzheimer's Disease Education and Referral (ADEAR) Center at www.nia.nih.gov/alzheimers.

About the NIH Common Fund: The NIH Common Fund encourages collaboration and supports a series of exceptionally high-impact, trans-NIH programs. Common Fund programs are managed by the Office of Strategic Coordination in the Division of Program Coordination, Planning, and Strategic Initiatives in the NIH Office of the Director in partnership with the NIH Institutes, Centers, and Offices. More information is available at the Common Fund website: https://commonfund.nih.gov.

About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.