Tadalafil as Adjuvant Therapy for DMD

NCT05195775 | Active Not Recruiting Phase 2 FDA Drug

• 2 other identifiers: IRB202102391OCR41391
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

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.

Conditions

Duchenne Muscular Dystrophy

Keywords

therapy; treatment strategy; vasodilator; exercise

Outcome Measures

Primary Outcomes (2)

• 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

• 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 Outcomes (1)

• Change in submaximal exercise capacity after tadalafil dosing

  Cycle testing will be done 4 hours after dosing/no-dosing on two separate study visits

Study Arms (2)

Tadalafil plus BOLD-MRI (Schedule A)

EXPERIMENTAL

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

Tadalafil plus Doppler ultrasound (Schedule B)

EXPERIMENTAL

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

Interventions

Tadalafil DRUG

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.

Also known as: Cialis

Tadalafil plus BOLD-MRI (Schedule A)

Eligibility Criteria

• Age: 7 Years - 13 Years
• Gender Eligibility Details: 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.
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• University of Florida: lead

Study Sites (1)

University of Florida

Gainesville, Florida, 32610, United States

Location

MeSH Terms

Conditions

Muscular Dystrophy, Duchenne; Motor Activity

Interventions

Tadalafil

Condition Hierarchy (Ancestors)

Muscular Dystrophies; Muscular Disorders, Atrophic; Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Behavior

Intervention Hierarchy (Ancestors)

Carbolines; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Indole Alkaloids; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds, 3-Ring

Study Officials

• Tanja Taivassalo

  University of Florida

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Pre/post single dose tadalafil

Study Record Dates

• First Submitted: January 4, 2022
• First Posted: January 19, 2022
• Study Start: December 14, 2021
• Primary Completion: September 5, 2025
• Study Completion: September 5, 2025
• Last Updated: February 27, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)