Tadalafil as Adjuvant Therapy for DMD

University of Florida

Status and phase

Active, not recruiting

Phase 3

Phase 2

Conditions

Duchenne Muscular Dystrophy

Treatments

Drug: Tadalafil

Study type

Interventional

Funder types

Other

Identifiers

NCT05195775

IRB202102391

OCR41391 (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment

25 estimated patients

Sex

Male

Ages

7 to 13 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

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

Exclusion criteria

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)