PDE5 Inhibition to Alleviate Functional Muscle Ischemia in Becker Muscular Dystrophy

Becker Muscular Dystrophy Clinical Trial

Official title:

PDE5 Inhibition to Alleviate Functional Muscle Ischemia in Becker Muscular Dystrophy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02207283
• Other study ID #: 27634
• Status: Completed
• Phase: Phase 4
• First received: July 28, 2014
• Last updated: July 25, 2016
• Start date: March 2012
• Est. completion date: December 2014

Study information

• Verified date: July 2016
• Source: Cedars-Sinai Medical Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: December 2014
• Est. primary completion date: December 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 15 Years to 55 Years

Eligibility

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)

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Becker Muscular Dystrophy
• Ischemia
• Muscular Dystrophies
• Muscular Dystrophy, Duchenne

Intervention

Drug:
• Tadalafil

• Placebo

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Cedars-Sinai Medical Center

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Forearm Muscle Water Content by MRI		Change from baseline 24-hours post treatment	No
Secondary	Change in muscle tissue oxygenation		change in reflex decrease in muscle oxygenation 3 hours post treatment	No