Clinical Trial: PDE5 Inhibition to Alleviate Functional Muscle Ischemia in Becker Muscular Dystrophy
Study Status: Completed
Recruit Status: Completed
Study Type: Interventional
Official Title: PDE5 Inhibition to Alleviate Functional Muscle Ischemia in Becker Muscular Dystrophy
Brief Summary: This study is intended to build on recent findings from our laboratory showing that a single dose of tadalafil (also known as Cialis) restored normal blood flow regulation in men with Becker muscular dystrophy. The investigators now wish to extend these findings by showing that the same dose of tadalafil will also prevent muscle injury and fatigue. Patients will take a single dose of tadalafil prior to exercising. Then doctors will measure whether the patients muscles receive more blood flow and are better protected during exercise.
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, and (b) non-invasive forearm blood flow studies (Near Infrared Spectroscopy, Doppler Ultrasound) before and after a brief bout of handgrip exercise. 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 randomized in a 3:1 fashion (tadalafil:placebo) and then asked to repeat the above laboratory procedures.
We plan to enroll 12 adult men with Becker muscular dystrophy and 8 healthy control subjects.
Sponsor: Cedars-Sinai Medical Center
Current Primary Outcome: Change in Forearm Muscle Water Content by MRI [ Time Frame: Change from baseline 24-hours post treatment ]
Original Primary Outcome: Same as current
Current Secondary Outcome: Change in muscle tissue oxygenation [ Time Frame: change in reflex decrease in muscle oxygenation 3 hours post treatment ]
Original Secondary Outcome: Same as current
Information By: Cedars-Sinai Medical Center
Dates:
Date Received: July 28, 2014
Date Started: March 2012
Date Completion:
Last Updated: July 25, 2016
Last Verified: July 2016
