Clinical trial NCT05195775: Tadalafil as Adjuvant Therapy for DMD
Official title: Tadalafil as an Adjuvant to Therapy for Duchenne Muscular Dystrophy
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
PHASE3
Conditions: Duchenne Muscular Dystrophy
Keywords: therapy
treatment strategy
vasodilator
exercise
Lead sponsor: University of Florida
Sponsor class: OTHER
First posted: 2022-01-19
Enrollment: 25
Sex: MALE
Minimum age (years): 7
Maximum age (years): 13
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Pre/post single dose tadalafil
Primary purpose: TREATMENT

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.

Eligibility criteria: 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)

Primary outcomes:
measure: Change in post-contractile BOLD response after tadalafil dosing
timeFrame: MRI will be done 3 hours after dosing/no-dosing on two separate study visits
measure: Change in post-exercise hyperemia after tadalafil dosing
timeFrame: Doppler ultrasound will be done 3 hours after dosing/no-dosing on two separate study visits
Secondary outcomes:
measure: Change in submaximal exercise capacity after tadalafil dosing
timeFrame: Cycle testing will be done 4 hours after dosing/no-dosing on two separate study visits
Other outcomes:
Locations:
city: Gainesville
country: United States
facility: University of Florida
state: Florida
Study officials:
affiliation: University of Florida
name: Tanja Taivassalo
role: PRINCIPAL_INVESTIGATOR
References: