Clinical Trial: Tadalafil in Becker Muscular Dystrophy
Study Status: Completed
Recruit Status: Completed
Study Type: Interventional
Official Title: Functional Muscle Ischemia and PDE5A Inhibition in Becker Muscular Dystrophy
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.
Detailed Summary:
There are 2 phases to this research project: (1) an initial baseline study to compare patients with Becker muscular dystrophy against healthy control subjects, and (2) a subsequent brief treatment trial only in the muscular dystrophy patients (healthy controls will not participate in this second phase of the study).
The baseline study involves an intake history, physical examination, and phlebotomy for blood chemistries and DNA followed by (a) MRI scans of the forearm muscles before and after a brief bout of handgrip exercise approximately 1-1.5 hours to complete), and (b) non-invasive forearm blood flow studies (Near Infrared Spectroscopy, Doppler Ultrasound) before and after a brief bout of handgrip exercise (approximately 3-5 hours to complete). Blood flow studies will be performed with the subject's lower body enclosed in an airtight chamber. Blood flow and oxygen delivery to the forearm muscles will be measured before and during application of lower body negative pressure at rest and during handgrip exercise. Lower body negative pressure simulates the blood flow changes that normally occur when a person sits up after lying down.
The results of the baseline study will determine which patients meet preset eligibility criteria to participate in the medication phase of the study. These criteria include (1) normal kidney and liver function tests and normal BNP levels (the latter to exclude heart failure), and (2) abnormal MRI and blood flow responses to handgrip exercise. Eligible patients will be asked to repeat the above laboratory procedures on two more study days: one day after receiving 2 pills of tadalafil (a PDE5A inhibitor that is longer-lasting than Viagra) and another day after receiving 2 placebo pills. Study procedures can be broken up into two separate days for scheduling purposes and/or to avoid fatigue. Pati
Sponsor: Cedars-Sinai Medical Center
Current Primary Outcome: Reflex decrease in muscle tissue oxygenation (i.e., adrenergic vasoconstriction) during rhythmic handgrip exercise measured by Near Infrared Spectroscopy (NIR). [ Time Frame: measured at a minimum of 2 week intervals for a minimum of 6 weeks total (for subjects with BMD) ]
Original Primary Outcome:
Current Secondary Outcome: Change in forearm muscle water content by magnetic resonance imaging (MRI). [ Time Frame: measured at a minimum of 2 week intervals for a minimum of 6 weeks total (for subjects with BMD) ]
Original Secondary Outcome:
Information By: Cedars-Sinai Medical Center
Dates:
Date Received: February 17, 2010
Date Started: January 2010
Date Completion:
Last Updated: August 19, 2013
Last Verified: August 2013
