Tadalafil as Adjuvant Therapy for DMD

• ClinicalTrials.gov Identifier: NCT05195775
• Recruitment Status: Recruiting
• First Posted: January 19, 2022
• Last Update Posted: March 2, 2022
• Sponsor: University of Florida
• Information provided by (Responsible Party): University of Florida

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	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 (Clinical Trial)
• Estimated Enrollment: 25 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Pre/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: December 14, 2021
• Estimated Primary Completion Date: October 2022
• Estimated Study Completion Date: October 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 Name: 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 Name: Cialis

Outcome Measures

Primary Outcome Measures :

1. Change in post-contractile BOLD response after tadalafil dosing [ Time Frame: MRI will be done 3 hours after dosing/no-dosing on two separate study visits ]
   MRI technique to measure microvascular function in skeletal muscle
2. Change in post-exercise hyperemia after tadalafil dosing [ Time Frame: 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 :

1. Change in submaximal exercise capacity after tadalafil dosing [ Time Frame: 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

• Ages Eligible for Study: 7 Years to 13 Years (Child)
• Sexes Eligible for Study: Male
• Gender Based Eligibility: Yes
• Gender Eligibility Description: Duchenne Muscular Dystrophy is an X-linked disorder, and therefore predominantly in males. As a result, we are limiting our children study participants to males.
• Accepts Healthy Volunteers: No

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)

Contacts and Locations

Locations

United States, Florida

University of Florida; Recruiting

Gainesville, Florida, United States, 32610

Contact: Tanja Taivassalo 352-294-8748 ttaivassalo@ufl.edu

Principal Investigator: Tanja Taivassalo

Sponsors and Collaborators

University of Florida

Investigators

• Principal Investigator: Tanja Taivassalo; University of Florida

More Information

• Responsible Party: University of Florida
• ClinicalTrials.gov Identifier: NCT05195775
• Other Study ID Numbers: IRB202102391; OCR41391 ( Other Identifier: UF OnCore )
• First Posted: January 19, 2022
• Last Update Posted: March 2, 2022
• Last Verified: February 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes

Keywords provided by University of Florida:

therapy; treatment strategy; vasodilator; exercise

Additional relevant MeSH terms:

Muscular Dystrophies; Muscular Dystrophy, Duchenne; Muscular Disorders, Atrophic; Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Tadalafil; Vasodilator Agents; Phosphodiesterase 5 Inhibitors; Phosphodiesterase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Urological Agents