Tadalafil in Becker Muscular Dystrophy

• Status: Completed
• Trial end date: 2012-12-01
• Target enrollment: 0
• Participant gender: Male

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.

• Phase: Phase 4
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Cedars-Sinai Medical Center
• Collaborator: Muscular Dystrophy Association
• Treatments: Tadalafil

Criteria

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)