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: Tamoxifen in Duchenne Muscular Dystrophy

Eligibility criteria:
Inclusion Criteria:

        Group A (ambulant patients)

          -  Documented diagnosis of DMD by mutation analysis in the dystrophin gene or by
             substantially reduced levels of dystrophin protein (i.e. absent or <5% of normal) on
             Western blot or immunostaining

          -  Stable treatment with glucocorticoids >6 months (no significant change in dosage
             (>0.2mg/kg)) at screening; dosing adaptations according to weight change are allowed

          -  Male gender

          -  6.5 to 12 years of age at time of screening

          -  weight >20kg

          -  ambulant patients

          -  able to walk at least 350 meters in 6 minute walking distance test without assistance
             at screening

          -  MFM D1 subdomain of the MFM scale >40% at screening

          -  Ability to provide informed consent and to comply with study requirements

          -  Patients harbouring a nonsense mutation treatable with the approved drug ataluren
             should be under stable ataluren treatment for at least 3 months or in case of
             nontolerance being off ataluren treatment for at least 3 months before screening

        Group B (non-ambulant patients)

          -  Documented diagnosis of DMD by mutation analysis in the dystrophin gene or by
             substantially reduced levels of dystrophin protein (i.e. absent or <5% of normal) on
             Western blot or immunostaining

          -  Not using glucocorticoids for >6 months

          -  Male gender

          -  Non-ambulant patients (walking distance less than 10 meters)

          -  10 to 16 years of age at time of screening

          -  Ability to provide informed consent and to comply with study requirements

        Open label extension

        - Recent participation and completion of TAMDMD study

        Exclusion Criteria:

          -  Known individual hypersensitivity or allergy to tamoxifen or other
             ingredients/excipients of IMP

          -  Female gender

          -  Use of tamoxifen or testosterone within the last 3 months

          -  Known or suspected malignancy

          -  Other chronic disease or clinically relevant limitation of renal, liver or heart
             function

          -  Known or suspected non-compliance

          -  Any injury which may impact functional testing, e.g. upper or lower limb fracture

          -  Planned or expected spinal fusion surgery during the study period (as judged by the
             Investigator; i.e. due to rapid progressing scoliosis), previous spinal fusion surgery
             is allowed if it took place more than 6 months prior to screening.

          -  Inability to follow the procedures of the study, e.g. due to language problems,
             psychological disorders of the participant/parents (as judged by the investigator)

          -  Concomitant participation in any other interventional trial (and up to 3 months prior
             to screening)

          -  Use of CYP2D6 inhibitors or of CYP3A4 inducers (apart from glucocorticoids), platelet
             aggregation inhibitors and coumarin-type anti-coagulants

          -  Use of drugs metabolized by CYP2C9, such as phenprocoumon, phenytoin, warfarin,
             celecoxib, fluvastatin, ginko biloba, St. John's wort and sulfamethoxazol

          -  Galactosemia (lack of galactose-1-phosphat-uridylyltransferase or
             UDP-galactose-4-epimerase or galactokinase; Fanconi-Bickel-syndrome); congenital lack
             of lactase; glucose-galactose malabsorption

          -  Presence of one or more of the following eye disorders: cataract, retinopathia, optic
             neuropathy, alteration of the cornea

          -  Presence of one or more of the following laboratory abnormalities: anaemia,
             thrombocytopenia, leukopenia, neutropenia or agranulocytosis

        Group A:

          -  Glucocorticoid naïve patients

          -  Start of glucocorticoid treatment or change in dosage <6 month prior to screening
             (dosing adaptations according to weight change are allowed)

        Group B:

          -  Glucocorticoid treated patients or patients that stopped glucocorticoid treatment <6
             month prior to screening

          -  Assisted ventilation of any kind necessary
Male
No healthy subjects accepted to join the trial.
Subject must be at least 78 Months old.
Subject must be at most 16 Years

Eligibility (NLI label): Entailment