Duchenne Muscular Dystrophy (DMD)
Conditions
Keywords
Duchenne muscular dystrophy, Obesity, Glucagon-Like Peptide-1 Receptor Agonists
Brief summary
Duchenne Muscular Dystrophy (DMD) is a rare, genetic disease that leads to muscle weakness, breathing difficulties, heart disease, and early death. Approximately half of individuals with DMD have elevated body mass indices (BMIs) in the overweight or obesity range. High BMI is due to a combination of factors including limited mobility and steroid medications, which are used to treat DMD. There are new medications, glucagon-like peptide-1 receptor agonists (GLP-1 RAs) that promote weight loss in the general population. GLP-1 RAs are approved for weight loss in children and adults and have beneficial effects on the heart. There is a concern that these medications could have unwanted side effects in individuals with DMD, specifically decreasing their muscle mass. While it is important to consider the use weight-loss medications in DMD, the investigators want to ensure that they are safe and well-tolerated. Therefore, this study will systematically evaluate whether the use of GLP-1 RAs in adolescents and young adults with DMD affects muscle mass. The overall goal of this study is to assess the safety and tolerability of GLP1-RAs in individuals with both DMD and obesity. The primary focus will be on muscle health, but the study will also evaluate activity levels, mood, gastrointestinal symptoms, and quality of life. Secondary goals will be to understand the impact of GLP1-RAs on weight, fat mass, glucose and insulin levels, and heart and lung function in individuals with DMD. The investigators hypothesize that GLP1-RAs will be well-tolerated and will decrease fat mass, without a large decrease in muscle mass. Participants will: * Take oral semaglutide or a placebo every day for 24 weeks (randomized controlled trial) * Then take oral semaglutide every day for 40 weeks (open label extension) * Complete in-person study visits at 3 timepoints * Study visits may include: an MRI of the body to evaluate muscle and fat tissue, laboratory testing, a mixed meal tolerance test, questionnaires, an MRI of the heart, pulmonary function tests, and additional measures * Calls with the study team between visits (monthly or every other month)
Interventions
Oral semaglutide will be provided as part of the RCT and subsequent open label extension. This will be taken as a daily medication following approved dose titration schedule.
OTHERPlacebo
oral placebo
Sponsors
Vanderbilt University Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
Randomized controlled trial (24 weeks) and subsequent open label extension (40 weeks).
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male * Age ≥18years * BMI ≥ 30kg/m2 or BMI ≥ 27kg/m2 with at least one weight-related comorbid condition (e.g., hypertension, T2D, or dyslipidemia). * Clinical phenotype of DMD confirmed with muscle biopsy or genotype
Exclusion criteria
* Type 1 diabetes, uncontrolled type 2 diabetes (HbA1c \>8%) or type 2 diabetes requiring the use of insulin or sulfonylurea. * History of pancreatitis * Personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia type 2 * History of allergic reaction to semaglutide or medication components * Contraindication to MRI. If unable to tolerate whole body/cardiac MRI but able to undergo lower extremity MRI, the participant may be invited to complete extremity MRI (Aim 1) and not complete MRI for Aim 2/3 (secondary Aims/outcomes) * Uncontrolled major depressive disorder, lifetime history of suicide attempt, history of other severe psychiatric disorders (e.g., schizophrenia, bipolar disorder), PHQ-9 score ≥15 or suicidal ideation type 4 or 5 (C-SSRS) * Unable to comply with study procedures or unsafe to complete the study in the opinion of the investigator
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Muscle Volume Index (MVI) | Week 0 (baseline), week 24 (end of RCT), week 64 (end of study) | Assessment of muscle mass via skeletal muscle MRI. Change in MVI from baseline to week 24 will be compared in those on placebo compared to those on semaglutide. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Visceral adiposity | Week 0 (baseline), week 24 (end of RCT), week 64 (end of study) | Visceral adiposity will be measured on whole-body MRI. Change in visceral fat area from baseline to week 24 will be compared in those on placebo compared to those on semaglutide.. |
| Weight | Week 0 (baseline), week 24 (end of RCT), week 64 (end of study) | Weight will be measured in kg. Change in weight from baseline to week 24 will be compared in those on placebo compared to those on semaglutide. |
| Insulin sensitivity | Week 0 (baseline), week 24 (end of RCT), week 64 (end of study) | Insulin sensitivity will be calculated from the mixed meal tolerance test. Change in insulin sensitivity from baseline to week 24 will be compared in those on placebo compared to those on semaglutide. |
| LVEF | Week 0 (baseline) and week 64 (end of study) | LVEF will be assessed via cardiac MRI. Change in LVEF over the course of the study will be calculated. |
| Late gadolinium enhancement (LGE) | Week 0 (baseline) and week 64 (end of study). | LGE, a measurement of myocardial fibrosis, will be assessed on cardiac MRI. Change in LGE over the course of the study will be calculated. |
| FVC% | Week 0 (baseline) and week 64 (end of study). | Percent predicted forced vital capacity will be evaluated with pulmonary function tests. Change in FVC% over the course of the study will be calculated. |
Countries
United States
Contacts
CONTACTJaclyn Tamaroff, MD
CONTACTJonathan Soslow, MD
Outcome results
None listed