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Tadalafil as Adjuvant Therapy for DMD

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

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.

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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


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




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.



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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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05195775


Locations
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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
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Principal Investigator: Tanja Taivassalo University of Florida
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Responsible Party: University of Florida
ClinicalTrials.gov Identifier: NCT05195775    
Other Study ID Numbers: IRB202102391
OCR41391 ( Other Identifier: UF OnCore )
First Posted: January 19, 2022    Key Record Dates
Last Update Posted: March 2, 2022
Last Verified: February 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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:
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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