Tadalafil in Becker Muscular Dystrophy

NCT01070511 | Completed Phase 4 DMC

• 1 other identifier: MDA 158944
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 2

Brief Summary

Summary for Patients: This study, funded by the Muscular Dystrophy Association, is intended to build on recent findings published in the journal Nature showing beneficial effects of tadalafil (also known as Cialis) in mice with an animal version of Duchenne and Becker muscular dystrophies. Only two doses of tadalafil improved muscle blood flow, allowing the dystrophic mice to perform more exercise with less muscle injury. This new short-term clinical trial will move the testing from animals to human patients with Becker muscular dystrophy and examine the effects of acute tadalafil dosing on muscle blood flow during a bout of exercise. Patients will take two doses of tadalafil prior to exercising. Then doctors will measure whether muscles receive increased blood flow and therefore are better protected during exercise. Scientific Hypothesis: In patients with Becker muscular dystrophy (particularly those with dystrophin gene mutations between exons 41-46), loss of sarcolemmal nitric oxide synthase engenders functional muscle ischemia and thus muscle edema after an acute bout of exercise. The investigators further hypothesize that PDE5A inhibition, which boosts nitric oxide-cGMP signaling, constitutes an effective new countermeasure for these patients.

Conditions

Becker Muscular Dystrophy

Keywords

Muscular Dystrophy; Tadalafil

Outcome Measures

Primary Outcomes (1)

• Reflex decrease in muscle tissue oxygenation (i.e., adrenergic vasoconstriction) during rhythmic handgrip exercise measured by Near Infrared Spectroscopy (NIR).

  measured at a minimum of 2 week intervals for a minimum of 6 weeks total (for subjects with BMD)

Secondary Outcomes (1)

• Change in forearm muscle water content by magnetic resonance imaging (MRI).

  measured at a minimum of 2 week intervals for a minimum of 6 weeks total (for subjects with BMD)

Study Arms (2)

Tadalafil

EXPERIMENTAL

Drug: Tadalafil

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Tadalafil DRUG

Tadalafil will be administered orally on two consecutive days. The first dose-10 mg- will be administered the afternoon before the study. The second dose -20 mg-will be administered the morning of the study.

Also known as: Cialis

Tadalafil

Placebo DRUG

A placebo pill will be administered orally on two consecutive days. The first pill will be administered the afternoon before the study. The second pill will be administered the morning of the study.

Placebo

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

Becker Muscular Dystrophy Patients * Men 18-55 years of age with a pre-existing diagnosis of Becker Muscular Dystrophy by a clinical neurologist (based on clinical criteria plus previous muscle biopsy analysis and/or DNA analysis). Healthy Controls * Men 18-55 years of age with no known medical conditions Criteria for exclusion of subjects (both patients and controls) * Any evidence of cardiopulmonary disease by history or by physical examination * History of hypertension or blood pressure averaging ≥140/90 mmHg * Diabetes mellitus or other systemic illness * Heart failure by clinical exam, elevated BNP, or heart failure medication * Serum creatinine ≥ 1.5 mg/dL * Any history of substance abuse (including alcohol) * Any history of psychiatric illness * Contraindications to tadalafil (use of nitrates, alpha-blockers, other PDE5A inhibitors, or potent inhibitors of CYP3A4 such as ketoconazole or ritonavir) * Contraindications to MRI (claustrophobia, metal implants, or seizure disorder)

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Cedars-Sinai Medical Center: lead
• Muscular Dystrophy Association: collaborator

Study Sites (2)

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

Location

Cedars Sinai Medical Center

Los Angeles, California, 9004, United States

Location

MeSH Terms

Conditions

Muscular Dystrophy, Duchenne; Muscular Dystrophies

Interventions

Tadalafil

Condition Hierarchy (Ancestors)

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

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

• Ronald G Victor, MD

  Cedars-Sinai Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director Hypertension Center

Study Record Dates

• First Submitted: February 17, 2010
• First Posted: February 18, 2010
• Study Start: January 1, 2010
• Primary Completion: December 1, 2012
• Study Completion: December 1, 2012
• Last Updated: August 20, 2013

Record last verified: 2013-08

Locations

US (2)