Tadalafil as Adjuvant Therapy for DMD

Sponsor

University of Florida (Other)

Overall Status

Recruiting

CT.gov ID

NCT05195775

Collaborator

(none)

Enrollment

Location

Arms

9.6

Anticipated Duration (Months)

2.6

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Duchenne Muscular Dystrophy	Drug: Tadalafil Drug: Tadalafil	Phase 2/Phase 3

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

25 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Pre/post single dose tadalafilPre/post single dose tadalafil

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Tadalafil as an Adjuvant to Therapy for Duchenne Muscular Dystrophy

Actual Study Start Date :

Dec 14, 2021

Anticipated Primary Completion Date :

Oct 1, 2022

Anticipated Study Completion Date :

Oct 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Tadalafil plus BOLD-MRI (Schedule A) 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.	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. Other Names: Cialis
Experimental: Tadalafil plus Doppler ultrasound (Schedule B) 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.	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 (Doppler US, exercise testing, clinical function) will be performed 3 hours after time of dosing. Other Names: Cialis

Arm

Intervention/Treatment

Experimental: Tadalafil plus BOLD-MRI (Schedule A)

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.

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.

Other Names:

Cialis

Experimental: Tadalafil plus Doppler ultrasound (Schedule B)

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.

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 (Doppler US, exercise testing, clinical function) will be performed 3 hours after time of dosing.

Other Names:

Cialis

Outcome Measures

Primary Outcome Measures

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

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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

7 Years to 13 Years

Sexes Eligible for Study:

Male

Accepts 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)