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Tadalafil and Sildenafil for Duchenne Muscular Dystrophy

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01359670
First Posted: May 25, 2011
Last Update Posted: August 20, 2013
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborator:
Parent Project Muscular Dystrophy
Information provided by (Responsible Party):
Ron Victor, Cedars-Sinai Medical Center
May 23, 2011
May 25, 2011
August 20, 2013
May 2011
May 2013   (Final data collection date for primary outcome measure)
Functional muscle ischemia [ Time Frame: For 5 study visits ]
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.
Same as current
Complete list of historical versions of study NCT01359670 on ClinicalTrials.gov Archive Site
  • Cardiac Function [ Time Frame: For 5 study visits ]
    Echocardiogram
  • EKG Monitoring [ Time Frame: 5 times over about 6 weeks ]
    48 hour Holter monitoring
  • 6 Minute Walk Test [ Time Frame: For 5 study visits ]
  • Physical Activity [ Time Frame: 5 times over about 6-weeks ]
    Assessed by accelerometers
  • Quality of Life [ Time Frame: For 5 study visits ]
    PedsQL inventory
Same as current
Not Provided
Not Provided
 
Tadalafil and Sildenafil for Duchenne Muscular Dystrophy
Functional Muscle Ischemia and PDE5A Inhibition in Duchenne Muscular Dystrophy
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.

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.

Interventional
Not Provided
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Duchenne Muscular Dystrophy
  • Drug: Tadalafil
    Escalating dose (0.25 mg/kg, 0.5 mg/kg, 1.0 mg/kg; once daily) over 2 weeks
    Other Names:
    • Cialis
    • Adcirca
  • Drug: Sildenafil
    Escalating dose (0.25 mg/kg, 0.5 mg/kg, 1.0 mg/kg; four times daily) over 2 weeks
    Other Names:
    • Viagra
    • Revatio
  • Experimental: Tadalafil
    Intervention: Drug: Tadalafil
  • Experimental: Sildenafil
    Intervention: Drug: Sildenafil
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
30
May 2013
May 2013   (Final data collection date for primary outcome measure)

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)
Sexes Eligible for Study: Male
7 Years to 15 Years   (Child)
No
Contact information is only displayed when the study is recruiting subjects
United States
 
 
NCT01359670
PPMD
No
Not Provided
Not Provided
Ron Victor, Cedars-Sinai Medical Center
Cedars-Sinai Medical Center
Parent Project Muscular Dystrophy
Principal Investigator: Ronald Victor, MD Cedars-Sinai Medical Center
Cedars-Sinai Medical Center
August 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP