Tadalafil and Sildenafil for Duchenne Muscular Dystrophy

Duchenne Muscular Dystrophy Clinical Trial

Official title:

Functional Muscle Ischemia and PDE5A Inhibition in Duchenne Muscular Dystrophy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01359670
• Other study ID #: PPMD
• Status: Completed
• Phase: Early Phase 1
• Start date: May 2011
• Est. completion date: May 2013

Study information

• Verified date: April 2018
• Source: Cedars-Sinai Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study, supported by Parent Project Muscular Dystrophy, will determine if tadalafil or sildenafil can improve muscle blood flow during exercise in boys with Duchenne muscular dystrophy.

Description:

Duchenne muscular dystrophy (DMD) is a rare, progressive and fatal muscle disease affecting boys and accounts for 80% of muscular dystrophy cases. Tadalafil and sildenafil are medications 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, but their benefit to boys with DMD is unknown. The purpose of this study is to 1) determine if tadalafil or sildenafil can improve muscle blood flow during exercise in boys with DMD; and 2) to inform the design of a subsequent, randomized, multi-center trial with clinical endpoints.

The investigators will enroll boys with DMD between the ages of 7 and 15 years who are ambulatory and without clinical heart failure. Participants will undergo 6 visits over the course of 5 weeks. The initial visit will include a medical history, physical exam, echocardiogram, and blood draw to determine eligibility for the study. Boys will be given a Holter monitor (a heart monitor) to wear for 48 hours to observe any irregular heartbeats or abnormalities.

Eligible boys will be randomized to one of the two study drugs: tadalafil or sildenafil. The boys will take a low dose (0.25mg/kg) of the study drug for the first 2 days and an intermediate dose (0.5mg/kg) for the subsequent 5 days. Then, boys will take a higher dose (1.0mg/kg) of the study drug for 1 week. Tadalafil will be taken once daily and sildenafil will be taken four times daily.

Study visits will occur 2 times at baseline, 2 times during the medication, and 1 time after washout of the medication. For these visits, boys will undergo an arm blood flow and hand grip exercise protocol. In this procedure, blood flow and oxygen delivery to the forearm muscles will be measured (noninvasively) before and during application of lower body negative pressure at rest and during handgrip exercise. Lower body negative pressure stimulates the blood flow changes that normally occur when a person sits up after lying down. During these visits, boys will complete a quality of life questionnaire, echocardiogram, and 6-minute walk tests. At home, boys will wear an accelerometer to measure physical activity and a Holter monitor to check for irregular heartbeats.

For boys who wish to continue with the study, there will be an option to cross-over and complete study visits with the drug they did not originally receive.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: May 2013
• Est. primary completion date: May 2013
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 7 Years to 15 Years

Eligibility

Inclusion Criteria:

1. Diagnosis of DMD confirmed by muscle biopsy or DNA analysis

2. Age 7-15y

3. Ambulatory

4. No clinical evidence of heart failure

Exclusion Criteria:

1. Hypertension, diabetes, or heart failure by standard clinical criteria

2. Elevated BNP level (>100 pg/ml)

3. LVEF < 50%

4. Wheelchair bound

5. Cardiac rhythm disorder, specifically: rhythm other than sinus, SVT, atrial fibrillation, ventricular tachycardia

6. Continuous ventilatory support

7. Liver disease

8. Renal impairment

9. Contraindications to tadalafil or sildenafil (use of nitrates, alpha-blockers, CYP3A inhibitors, amlodipine, or other PDE5A inhibitors)

Related Conditions & MeSH terms

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

Intervention

Drug:
• Tadalafil
Escalating dose (0.25 mg/kg, 0.5 mg/kg, 1.0 mg/kg; once daily) over 2 weeks
• Sildenafil
Escalating dose (0.25 mg/kg, 0.5 mg/kg, 1.0 mg/kg; four times daily) over 2 weeks

Locations

Country	Name	City	State
United States	Cedars-Sinai Medical Center	Los Angeles	California

Sponsors (2)

Lead Sponsor	Collaborator
Cedars-Sinai Medical Center	Parent Project Muscular Dystrophy

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Functional muscle ischemia	Measured by the decrease in muscle tissue oxygenation (near infrared spectroscopy) and blood flow (Doppler ultrasound) evoked by reflex sympathetic activation in exercising forearm muscle.	For 5 study visits
Secondary	Cardiac Function	Echocardiogram	For 5 study visits
Secondary	EKG Monitoring	48 hour Holter monitoring	5 times over about 6 weeks
Secondary	6 Minute Walk Test		For 5 study visits
Secondary	Physical Activity	Assessed by accelerometers	5 times over about 6-weeks
Secondary	Quality of Life	PedsQL inventory	For 5 study visits