Functional Muscle Ischemia With Tadalafil Treatment in Becker Muscular Dystrophy

Becker Muscular Dystrophy Clinical Trial

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT03076814
• Other study ID #: PRO27634
• Status: Withdrawn
• Phase: N/A
• First received: September 23, 2014
• Last updated: October 15, 2017
• Start date: March 2012
• Est. completion date: December 2015

Study information

• Verified date: October 2017
• Source: Cedars-Sinai Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

the Investigator will test the hypothesis that short term PDE5A inhibition (with tadalafil) will reduce post-exercise edema by MRI in males with Becker Muscular Dystrophy.

Description:

Becker muscular dystrophy (BMD) is a rare, progressive and fatal muscle disease. Tadalafil is approved by the FDA for the treatment of erectile dysfunction and pulmonary hypertension. This class of medication improves muscle blood flow in a mouse model of muscular dystrophy, prevents post-exercise muscle edema, and alleviates post-exercise muscle fatigue. To begin to translate this work from the mouse into actual patients with muscular dystrophy, the Investigator group recently demonstrated that a single dose of tadalafil can improve blood flow regulation in boys with Duchenne muscular dystrophy and men with BMD. the Investigator now wish to test the hypothesis that acute treatment with Tadalafil can prevent post-exercise muscle edema in men with BMD.

the Investigator will recruit men with BMD, and healthy age-matched controls, ages 15-55y who are ambulatory and without heart failure.

Visit 1: Participants will undergo informed consent, physical exam and medical history screening, electrocardiogram, blood pressure monitoring, blood chemistry testing, echocardiogram (ejection fraction measurement), and evaluation of skeletal muscle blood flow. Patients, but not controls, will also undergo a muscle biopsy.

Visit 2 - 4: Participants will undergo baseline magnetic resonance imaging of the forearm muscle, followed by rhythmic forearm muscle exercise (handgrip). MRI will then be repeated 2-, 4-, 24-, and 48 hours following the rhythmic handgrip exercise.

Patients with BMD will then be randomized in a 3:1 fashion to tadalafil vs. placebo.

Visit 5-7: Using a standard double-blind cross-over design, patients will be treated with either tadalafil or placebo. Magnetic resonance imaging of the forearm muscle will be performed to establish baseline measurements. Patients will then repeat the rhythmic handgrip exercise protocol performed on Visit 2, followed by MRI 2-, 4-, 24-, and 48 hours following exercise.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: December 2015
• Est. primary completion date: December 2015
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 15 Years to 55 Years

Eligibility

Patient with BMD -

Inclusion Criteria:

• diagnosis of BMD confirmed by muscle biopsy or DNA analysis

• age 15-55 years of age

• ambulatory

• no clinical evidence of heart failure

Exclusion Criteria:

• hypertension, diabetes, or heart failure by standard clinical criteria

• elevated BNP (brain natriuretic peptide) level (>100 pg/ml)

• left ventricular ejection fraction < 50%

• wheelchair bound

• cardiac rhythm disorder, specifically: rhythm other than sinus, sinoventricular tachycardia, atrial fibrillation, ventricular tachycardia

• continuous ventilatory support

• liver disease

• renal impairment

• contraindications to tadalafil (use of nitrates, alpha-blockers, Cytochrome P450 (CYP3A )inhibitors, amlodipine, or other phosphodiesterase 5A inhibitors)

Healthy Control Participants -

Inclusion Criteria:

• age 15-55 years of age

• ambulatory

• no clinical evidence of heart failure

Exclusion Criteria:

• hypertension, diabetes, or heart failure by standard clinical criteria

• elevated BNP (brain natriuretic peptide) level (>100 pg/ml)

• left ventricular ejection fraction < 50%

• cardiac rhythm disorder, specifically: rhythm other than sinus, sinoventricular tachycardia, atrial fibrillation, ventricular tachycardia

• liver disease

• renal impairment

• unsatisfactory completion of the sympatholysis protocol

• BMI < 35

Related Conditions & MeSH terms

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

Intervention

Drug:
• Tadalafil

Other:
• 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 post-exercise muscle edema by MRI.		Pre vs. 48 hours post treatment change