About half of patients with Duchenne muscular dystrophy (DMD), a life-limiting disease with limited therapeutic options and no cure, have elevated body mass indexes (BMI) in the overweight or obesity range due to a combination of factors including limited mobility and steroid medications.
Researchers at Monroe Carell Jr. Children’s Hospital at Vanderbilt hope a new study will change that.
Jaclyn Tamaroff, MD, MSCI, and Jonathan Soslow, MD, MSCI, Co-Director of the DMD Clinic at Monroe Carell, are co-leading a study evaluating the safety and tolerability of glucagon-like peptide-1 (GLP-1) receptor agonist drugs in patients with DMD and obesity.
“Individuals with DMD are at high risk for increased weight and obesity,” said Tamaroff, Assistant Professor of Pediatrics in the Ian M. Burr Division of Pediatric Endocrinology and Diabetes at Monroe Carell. “What we will be highly focused on is muscle health. There is concern that these medications could have unwanted side effects in individuals with DMD. Specifically, it is unknown what their impact will be on muscle mass.
“We want to be sure that this medication is tolerated and safe while decreasing fat mass without a large decrease in muscle mass.”
The single-center, randomized controlled trial, “Glucagon-Like Peptide-1 Receptor Agonists to Attenuate Metabolic Risk in Individuals with Duchenne Muscular Dystrophy,” is funded by a four-year, $1.9 million Department of Defense grant.
The team will begin enrolling eligible patients in September. Thirty participants, ages 12 and older, will be randomized to receive either a placebo or the GLP-1 receptor agonist semaglutide during a 24-week period, followed by a 40-week, open-label extension allowing all participants to receive the medication.
“What is exciting about this study is that we are using a medication that is clinically approved for the age of patients we are enrolling,” said Tamaroff. “While we are focused on the impact on muscle, we are also looking at gastrointestinal side effects, metabolic effects, cardiac and pulmonary function, mood, activity levels and quality of life.”
DMD — a rare, genetic disease — leads to muscle weakness, breathing difficulties, heart disease and early death.
“GLP-1 receptor agonists may promote healthy weight loss, improve quality of life and functional status, and benefit cardiometabolic health in individuals with DMD,” she said.
Tamaroff said study findings would be immediately clinically applicable to individuals with DMD with elevated BMIs.
There is also potential that the findings of this study could reach beyond those living with DMD, including those with other neuromuscular disorders and causes of low muscle mass with elevated weight or cardiac concerns.
“This may impact service members and veterans,” she said. “It could also directly impact those with spinal cord injuries. This study could have far-reaching relevance.”
This is the second DOD grant for Soslow, who is partnering with the Critical Path Institute to advance the study of cardiomyopathy in DMD, the leading cause of death in this patient population. Soslow, Professor of Pediatrics at Monroe Carell, holds the Dr. William R. Long Directorship in Pediatric Research.
Fatemeh Adelnia, PhD, Research Assistant Professor of Radiology and Radiological Sciences at Vanderbilt Health, will serve as a co-investigator. Study participants will receive three MRIs to look at fat and muscle mass and two MRIs to look at the heart.
For more information on the study (NCT07642635), please contact Tamaroff at Jacyln.tamaroff@vumc.org.
