Tadalafil and Sildenafil for Duchenne Muscular Dystrophy
Condition: Duchenne Muscular Dystrophy
MeSH terms: Muscular Dystrophies; Muscular Dystrophy, Duchenne
Study type: Interventional
Phase: Early Phase 1

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.
    

Detailed 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.
    

Intervention name(s): Tadalafil; Sildenafil
Intervention type(s): Drug; Drug
Intervention description(s): Escalating dose (0.25 mg/kg, 0.5 mg/kg, 1.0 mg/kg; once daily) over 2 weeks; Escalating dose (0.25 mg/kg, 0.5 mg/kg, 1.0 mg/kg; four times daily) over 2 weeks
Other intervention name(s): Cialis; Adcirca; Viagra; Revatio
Intervention MeSH terms: Sildenafil Citrate; Tadalafil
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Duchenne; muscular dystrophy; tadalafil; sildenafil; muscle ischemia; exercise