Patient case (clinical description): An 8-year-old boy is brought to the clinic by his parents because of weakness and difficulty of standing up from a sitting position. The mother is healthy but had a brother who died in his 20th after being disabled and using wheelchairs in the last few years of his life. Physical examination shows 3/5 lower extremity muscle strength and enlarged calf muscles. The other physical examination and vital signs are unremarkable. Muscle biopsy showed absence of dystrophin protein. The patient is diagnosed with DMD.

Patient's own account: I brought my  8-year-old son to the doctor's clinic. He was struggling to stand up from a chair for the past few days. My wife is healthy but she was pretty worried since his brother died in his 20s after being disabled and using a wheelchair for the last years of his life. The doctor did an exam which highlighted weakness in the leg muscles and unusually large calf muscles. The rest of the exam was fine, and his vitals were normal. My son did a muscle biopsy, and it showed that the protein important for muscle strength and function is missing. The doctor diagnosed him with Duchenne muscular dystrophy.

Clinical trial: A Study of Tadalafil for Duchenne Muscular Dystrophy

Eligibility criteria:
Inclusion Criteria:

          -  Ambulant males with Duchenne muscular dystrophy (DMD) confirmed by typical clinical
             presentation (onset of clinical signs or symptoms before 6 years of age supported by
             an elevated serum creatinine kinase level, and ongoing difficulty with walking)
             together with either a record of a genetic confirmation of the DMD diagnosis, or a
             record of muscle biopsy showing near-complete dystrophin deficiency (excluding
             revertant fibers)

          -  Receiving systemic corticosteroids for a minimum of 6 months immediately prior to
             screening, with no significant change in total daily dosage or dosing regimen (except
             those adjusting for weight changes) for a minimum of 3 months immediately prior to
             screening and a reasonable expectation that total daily dosage and dosing regimen will
             not change significantly (except for adjustments for weight) for the duration of the
             study

          -  Able to complete the six minute walk distance (6MWD) test with results within 20% of
             each other at a minimum of 2 pre-randomization assessments

          -  Left ventricular ejection fraction (LVEF) ≥50% as determined by echocardiogram

          -  Written informed consent from parents/legal guardian will be obtained prior to any
             study procedure being performed. In addition, the child may be required to give
             documented assent, if capable.

        Exclusion Criteria:

          -  Symptomatic cardiomyopathy or heart failure

          -  Change in prophylactic treatment for heart failure within 3 months prior to start of
             study treatment

          -  Cardiac rhythm disorder

          -  History of participation in gene or cell-based therapy , or antisense oligonucleotide
             or stop codon read-through therapy

          -  Unable to take orally administered tablets

          -  Use of any pharmacologic treatment, other than corticosteroids, that might have an
             effect on muscle strength within 3 months prior to the start of study treatment (for
             example, growth hormone, anabolic steroids including testosterone)

          -  New or changed treatment with herbal or dietary supplements being taken with an
             expectation of an effect on muscle strength or function during 1 month prior to first
             dose of study drug

          -  Surgery that might have an effect on muscle strength or function within 3 months
             before study entry or planned surgery at any time during the study

          -  Evidence of a lower limb injury that may affect performance on the 6MWD

          -  Severe behavioral problems, including severe autism or attention deficit disorders,
             that may interfere with completion of the 6MWD

          -  Any contraindication to tadalafil (use of any form of organic nitrate, either
             regularly and/or intermittently, or known serious hypersensitivity to tadalafil)

          -  History of significant renal insufficiency or clinical evidence of cirrhosis

          -  Have known allergy to any of the excipients in tadalafil tablets, notably lactose

          -  Current Phosphodiesterase Type 5 (PDE5) inhibitor therapy or treatment within the past
             6 months
Male
No healthy subjects accepted to join the trial.
Subject must be at least 7 Years old.
Subject must be at most 14 Years

Eligibility (NLI label): Entailment