Revatio for Heart Disease in Duchenne Muscular Dystrophy and Becker Muscular Dystrophy
Condition: Duchenne Muscular Dystrophy; Becker Muscular Dystrophy
MeSH terms: Muscular Dystrophies; Muscular Dystrophy, Duchenne
Intervention: Sildenafil
Intervention description: 20mg tablet three times daily
Intervention MeSH terms: Sildenafil Citrate
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 20.0
Sex: Male
Minimum age: 18 Years
Maximum age: 50 Years
Healthy volunteers: No
Keywords: Clinical trial; Revatio; Sildenafil; Muscular Dystrophy; Duchenne; Becker; Adult; Adolescent

Summary:

      This study, supported by Charley's Fund, Inc., is being done to determine if the drug
      Revatio®(also known as Sildenafil), as compared to placebo (an inactive substance that looks
      like the study drug, but contains no medication), improves heart function in people with
      Duchenne Muscular Dystrophy and Becker Muscular Dystrophy (DBMD).

      In people with DBMD, dystrophin is not present or lacking in heart and muscle. This is
      associated with abnormalities in an enzyme called "neuronal nitric oxide synthase" or nNOS,
      and leads to decreases in "cyclic GMP," which is necessary for proper function of those
      muscles. Revatio blocks an enzyme called phosphodiesterase 5 (PDE5), and helps to restore the
      normal amounts of cyclic GMP. The purpose of this research is to determine if Revatio is safe
      for people with DBMD and if it can improve heart function.

      Hypothesis : PDE5 inhibition, with the use of Revatio, will improve cardiac function in
      patients with DBMD.
    

Eligibility criteria:

        Inclusion Criteria:

          1. DBMD as determined by either a skeletal muscle biopsy demonstrating absence or lack of
             dystrophin, and/or genetic testing showing a mutation in the dystrophin gene
             predictive of DBMD, as well as a consistent physical examination

          2. Male gender

          3. Age greater than or equal to 18 years

          4. Cardiac dysfunction with ejection fraction less than or equal to 50% as determined by
             echocardiogram, cardiac MRI, or multi-gated acquisition (MUGA) scan

          5. On a stable dose of ACE-inhibitor or angiotensin receptor blocker (ARB) for at least 3
             months; beta-adrenergic receptor blockers and glucocorticosteroids are not required
             but if used, a stable dose for at least 3 months is required.

          6. Ability of the subject or legal guardian to provide informed consent

          7. Ability to adhere with study follow-up

          8. Willingness to abstain from food and alcohol for 8 hours prior to FMD

        Exclusion Criteria:

          1. Use of nitrates or alpha-adrenergic receptor blockers

          2. Known intolerance or allergy to sildenafil, or a history of any severe allergic or
             anaphylactic reactions

          3. Any medical or psychosocial condition, which, in the view of the study investigator,
             makes study participation inadvisable

          4. Known hereditary retinal disorder such as retinitis pigmentosa

          5. History of priapism or conditions that may predispose to priapism such as sickle cell
             anemia, multiple myeloma, or leukemia

          6. Bleeding disorders

          7. Active tobacco use

          8. Chronic atrial fibrillation or frequent arrhythmia that would result in an irregular
             pulse

          9. Factors that would preclude obtaining an MRI study - (e.g. implantable pacemaker or
             cardioverter-defibrillator; body habitus cannot fit into scanner)

         10. Systolic blood pressure (SBP) less than 85 mmHg at baseline evaluation

         11. Chronic kidney disease stages 4 and 5: GFR< 30 mL/min/1.73 m2 as determined by serum
             cystatin C level and the equation eGFRcys = 76.7 x (serum cystatin C-1.18)

         12. Current use of sildenafil.