Vasodilator and Exercise Study for DMD (VASO-REx)

NCT ID: NCT06290713

Last Updated: 2025-07-09

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-06-05
• Study Completion Date: 2026-11-30

Brief Summary

Examining two strategies as potential adjuvant therapies for Duchenne muscular dystrophy (DMD); aerobic exercise training (to induce adaptations in skeletal muscle and improve cardiovascular health) and tadalafil, an FDA-approved vasodilator (to optimize blood flow and muscle perfusion which is impaired and often overlooked in DMD). Target: improved muscle function, vascular health, and DMD treatment.

Detailed Description

Duchenne muscular dystrophy (DMD) is characterized by rapid muscle deterioration, mitochondrial and vascular impairments, resulting in premature loss of ambulation and mortality. Disease-modifying therapeutics are emerging and although they are expected to improve muscle function and daily activity in boys with DMD, most are not designed to correct the vascular impairment. This impairment is due to the lack of restoration of neuronal nitric oxide synthase signaling, which is crucial for vasodilation during and after exercise. The investigators believe limitations in study design were responsible for the lack of efficacy. Therefore, this study combines tadalafil with aerobic exercise to necessitate increased blood flow and activate the drug.

This Exploratory Clinical Trial will assess two potential adjuvant therapies for ambulatory boys with DMD (6 years and older): 1) aerobic exercise training and 2) tadalafil, an FDA-approved vasodilator drug. Preclinical and clinical data, including recent findings from the principal investigator's lab, support the use of these strategies and their potential to benefit muscle perfusion, fatigue, and quality of life.

The study will first test for drug responsiveness (increase in muscle oxygenation) after a single dose. Drug-responsive boys with DMD will be randomized to a 6-month intervention of daily tadalafil or placebo, combined with structured cycle exercise training. Participants will receive exercise-related equipment for use at home and be monitored by the research team via video. The study will quantify the intervention's impact on vascular impairment, muscle pathophysiology (inflammation, fat accumulation, mitochondrial dysfunction), exertional fatigue, and cycling performance.

Our findings are expected to yield:

1. Criteria to identify DMD patients most likely to benefit from tadalafil as adjuvant therapy.

2. Evidence of a powerful synergy between drug impact and exercise training in DMD.

Conditions

Duchenne Muscular Dystrophy; Duchenne Disease; Muscular Dystrophy; Muscular Dystrophy in Children; Vasodilation; Exercise; DMD

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Tadalafil and Exercise Arm

Participants receive tadalafil weight-dependent dosage to take daily for 6 months (26 weeks).

Group Type: EXPERIMENTAL

Tadalafil

Intervention Type: DRUG

Patients will be given either the intervention medication or a placebo (double-blinded, randomized trial) and will be asked to take the medication every day for 6 months in conjunction with weekly exercise sessions.

Exercise Training

Intervention Type: OTHER

The home-based cycling exercise training program is designed to improve muscle strength and endurance. Participants will engage in individualized exercise sessions up to four times per week, lasting up to 40 minutes each. Live video and heart rate monitoring will ensure proper exercise performance and allow for adjustments to the program throughout the study. The participants will receive the exercise equipment for use at home.

Placebo and Exercise Arm

Participants receive a tadalafil placebo tablet matching the tadalafil weight-dependent dosage to take daily for 6 months (26 weeks).

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Patients will be given either the intervention medication or a placebo (double-blinded, randomized trial) and will be asked to take the medication every day for 6 months in conjunction with weekly exercise sessions.

Exercise Training

Intervention Type: OTHER

The home-based cycling exercise training program is designed to improve muscle strength and endurance. Participants will engage in individualized exercise sessions up to four times per week, lasting up to 40 minutes each. Live video and heart rate monitoring will ensure proper exercise performance and allow for adjustments to the program throughout the study. The participants will receive the exercise equipment for use at home.

Interventions

Tadalafil

Patients will be given either the intervention medication or a placebo (double-blinded, randomized trial) and will be asked to take the medication every day for 6 months in conjunction with weekly exercise sessions.

Intervention Type: DRUG

Placebo

Patients will be given either the intervention medication or a placebo (double-blinded, randomized trial) and will be asked to take the medication every day for 6 months in conjunction with weekly exercise sessions.

Intervention Type: DRUG

Exercise Training

The home-based cycling exercise training program is designed to improve muscle strength and endurance. Participants will engage in individualized exercise sessions up to four times per week, lasting up to 40 minutes each. Live video and heart rate monitoring will ensure proper exercise performance and allow for adjustments to the program throughout the study. The participants will receive the exercise equipment for use at home.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Diagnosis of DMD confirmed by genetic report
• Minimum entry age of 6.0 years old
• Ambulatory
• On stable glucocorticoid regimen (for > 3 months)

Exclusion Criteria

• Contraindication to a Magnetic resonance Imaging examination (e.g. severe claustrophobia, magnetic implants, unable/unwilling to perform test)
• Presence of unstable medical problems, including severe cardiomyopathy, left ventricular ejection fraction <45%, cardiac conduction abnormalities as evidenced on ECG, uncontrolled seizure disorder, uncontrolled hypo or hypertension
• Presence of a secondary condition that impacts muscle function or muscle metabolism (e.g., myasthenia gravis, endocrine disorder, mitochondrial disease)
• Presence of a secondary condition leading to developmental delay or impaired motor control (e.g., cerebral palsy) or previous history of unprovoked rhabdomyolysis
• Contraindications to phosphodiesterase 5 inhibitors (use of nitrates, alpha-adrenergic blockers, other phosphodiesterase 5 inhibitors) or other medications known to modulate blood flow or muscle metabolism
• Participation in currently approved FDA trials or other investigational clinical trials during the period of the study

• Minimum Eligible Age: 6 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

NIH

Sponsor Role: collaborator

University of Florida

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Tanja Taivassalo, Ph.D.

Role: PRINCIPAL_INVESTIGATOR

University of Florida, College of Medicine, Department of Physiology and Aging

Locations

University of Florida Clinical and Translational Research Building

Gainesville, Florida, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Tanja Taivassalo, Ph.D.

Role: CONTACT

ttaivassalo@ufl.edu

352-294-8748

Ruby Sullivan, MS

Role: CONTACT

r.sullivan1@ufl.edu

352-294-5392

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Other Identifiers

1R21AR079755-01

Identifier Type: NIH

Identifier Source: secondary_id

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PRO00050023

Identifier Type: OTHER

Identifier Source: secondary_id

IRB202301491

Identifier Type: -

Identifier Source: org_study_id