Tadalafil as Adjuvant Therapy for DMD
- Registration Number
- NCT05195775
- Lead Sponsor
- University of Florida
- Brief Summary
This project will assess the vascular responsiveness in leg muscles of boys with Duchenne muscular dystrophy (DMD) to one single dose of tadalafil, a common vasodilator drug, using non-invasive techniques (MRI or Doppler ultrasound) and exercise testing. These findings will provide proof of concept for a subsequent intervention study to demonstrate efficacy of longer-term tadalafil to counter sympathetic vasoconstriction and slow disease progression in DMD. It will also inform whether a group of patients do not respond to the drug.
- Detailed Description
This project will target up to 25 ambulatory boys with DMD aged 7-13 years. Because the vascular impact of tadalafil is immediate, we will confirm that the drug target is valid target in lower extremities by assessing the change in post-exercise microvascular perfusion using Blood Oxygen Level-Dependent (BOLD) MRI or change in post-exercise hyperemia using Doppler ultrasonography. We will also assess the functional impact of the drug through exercise testing. Patients will be randomized to undergo the above-mentioned assessments with or without the study drug on two separate visits. Time function tests, MRI-based fat fraction and inflammation measurements will also be obtained in all patients, thus characterizing disease severity and provide a sampling of information on whether a subset of patients do not respond to the drug. This information may be used to inform future trials as to the appropriate target population for PDE5i as well as account for potential failures in a previously published phase 3 clinical trial.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- Male
- Target Recruitment
- 25
- Diagnosis of DMD confirmed by 1) clinical history with features before the age of five, 2) physical examination, 3) elevated serum creatine kinase level and 4) absence of dystrophin expression, as determined by immunostaining or Western blot (<2%) and/or DNA confirmation of dystrophin mutation.
- Minimum entry age of 7.0 years
- Ambulatory
- Older than 13.0 years of age
- Contraindication to an MR examination (e.g. aneurysm clip, severe claustrophobia, magnetic implants)
- Presence of unstable medical problems
- Presence of a secondary condition that impacts muscle function or muscle metabolism (e.g. myasthenia gravis, endocrine disorder, mitochondrial disease)
- Contraindications to Tadalafil (use of nitrates, alpha-adrenergic blockers, other PDE5A inhibitors)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Tadalafil plus Doppler ultrasound (Schedule B) Tadalafil The intervention is the same as in Schedule A; this arm will use Doppler ultrasound as the technique to monitor drug impact on skeletal muscle. Tadalafil plus BOLD-MRI (Schedule A) Tadalafil The intervention is the same as in Schedule B; this arm will use BOLD-MRI as the technique to monitor drug impact on skeletal muscle.
- Primary Outcome Measures
Name Time Method Change in post-contractile BOLD response after tadalafil dosing MRI will be done 3 hours after dosing/no-dosing on two separate study visits MRI technique to measure microvascular function in skeletal muscle
Change in post-exercise hyperemia after tadalafil dosing Doppler ultrasound will be done 3 hours after dosing/no-dosing on two separate study visits Doppler ultrasound will be used to measure blood flow
- Secondary Outcome Measures
Name Time Method Change in submaximal exercise capacity after tadalafil dosing Cycle testing will be done 4 hours after dosing/no-dosing on two separate study visits incremental cardiopulmonary exercise testing on cycle ergometer will be performed to measure heart rate and parameters of exercise performance.
Trial Locations
- Locations (1)
University of Florida
🇺🇸Gainesville, Florida, United States