Glucagon-Like Peptide-1 Receptor Agonists to Attenuate Metabolic Risk in Individuals With Duchenne Muscular Dystrophy

NCT07642635 | Not Yet Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 260611
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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)

Conditions

Duchenne Muscular Dystrophy (DMD)

Keywords

Duchenne muscular dystrophy; Obesity; Glucagon-Like Peptide-1 Receptor Agonists

Outcome Measures

Primary Outcomes (1)

• Muscle Volume Index (MVI)

  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.

  Week 0 (baseline), week 24 (end of RCT), week 64 (end of study)

Secondary Outcomes (6)

• Visceral adiposity

  Week 0 (baseline), week 24 (end of RCT), week 64 (end of study)

• Weight

  Week 0 (baseline), week 24 (end of RCT), week 64 (end of study)

• Insulin sensitivity

  Week 0 (baseline), week 24 (end of RCT), week 64 (end of study)

• LVEF

  Week 0 (baseline) and week 64 (end of study)

• Late gadolinium enhancement (LGE)

  Week 0 (baseline) and week 64 (end of study).

Study Arms (3)

Semaglutide (RCT)

EXPERIMENTAL

oral semaglutide (24 week RCT)

Drug: Semaglutide (Rybelsus®)

Placebo (RCT)

PLACEBO COMPARATOR

oral placebo (24 week RCT)

Other: Placebo

Semaglutide (OLE)

EXPERIMENTAL

oral semaglutide (40 week open label extension)

Drug: Semaglutide (Rybelsus®)

Interventions

Semaglutide (Rybelsus®) DRUG

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.

Also known as: Wegovy

Semaglutide (OLE); Semaglutide (RCT)

Placebo OTHER

oral placebo

Placebo (RCT)

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Vanderbilt University Medical Center: lead

Study Sites (1)

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

MeSH Terms

Conditions

Muscular Dystrophy, Duchenne; Obesity

Interventions

semaglutide

Condition Hierarchy (Ancestors)

Muscular Dystrophies; Muscular Disorders, Atrophic; Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Jaclyn Tamaroff, MD

CONTACT

615-875-7853; Jaclyn.tamaroff@vumc.org

Jonathan Soslow, MD

CONTACT

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Randomized controlled trial (24 weeks) and subsequent open label extension (40 weeks).

Study Record Dates

• First Submitted: June 4, 2026
• First Posted: June 11, 2026
• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): September 1, 2030
• Study Completion (Estimated): December 1, 2030
• Last Updated: June 11, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)