Tadalafil as Adjuvant Therapy for DMD

Duchenne Muscular Dystrophy Clinical Trial

Official title:

Tadalafil as an Adjuvant to Therapy for Duchenne Muscular Dystrophy

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05195775
• Other study ID #: IRB202102391
• Secondary ID: OCR41391
• Status: Recruiting
• Phase: Phase 2/Phase 3
• Start date: December 14, 2021
• Est. completion date: January 20, 2025

Study information

• Verified date: January 2024
• Source: University of Florida
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 25
• Est. completion date: January 20, 2025
• Est. primary completion date: October 20, 2024
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 7 Years to 13 Years

Eligibility

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)

Related Conditions & MeSH terms

• Duchenne Muscular Dystrophy
• Muscular Dystrophies
• Muscular Dystrophy, Duchenne

Intervention

Drug:
• Tadalafil
Patient will be randomized to one dose of 0.6 mg/kg tadalafill on one of two study visits. On both visits, assessments (MRI, exercise testing, clinical function) will be performed 3 hours after time of dosing.
• Tadalafil
Patient will be randomized to one dose of 0.6 mg/kg tadalafill on one of two study visits. On both visits, assessments (Doppler US, exercise testing, clinical function) will be performed 3 hours after time of dosing.

Locations

Country	Name	City	State
United States	University of Florida	Gainesville	Florida

Sponsors (1)

Lead Sponsor	Collaborator
University of Florida

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in post-contractile BOLD response after tadalafil dosing	MRI technique to measure microvascular function in skeletal muscle	MRI will be done 3 hours after dosing/no-dosing on two separate study visits
Primary	Change in post-exercise hyperemia after tadalafil dosing	Doppler ultrasound will be used to measure blood flow	Doppler ultrasound will be done 3 hours after dosing/no-dosing on two separate study visits
Secondary	Change in submaximal exercise capacity after tadalafil dosing	incremental cardiopulmonary exercise testing on cycle ergometer will be performed to measure heart rate and parameters of exercise performance.	Cycle testing will be done 4 hours after dosing/no-dosing on two separate study visits