title: Somatropin treatment of spinal muscular atrophy: a placebo-controlled, double-blind crossover pilot study.
abstract: In preclinical studies growth hormone and its primary mediator IGF-1 have shown potential to increase muscle mass and strength. A single patient with spinal muscular atrophy reported benefit after compassionate use of growth hormone. Therefore we evaluated the efficacy and safety of growth hormone treatment for spinal muscular atrophy in a multicenter, randomised, double-blind, placebo-controlled, crossover pilot trial. Patients (n = 19) with type II/III spinal muscular atrophy were randomised to receive either somatropin (0.03 mg/kg/day) or placebo subcutaneously for 3 months, followed by a 2-month wash-out phase before 3 months of treatment with the contrary remedy. Changes in upper limb muscle strength (megascore for elbow flexion and hand-grip in Newton) were assessed by hand-held myometry as the primary measure of outcome. Secondary outcome measures included lower limb muscle strength, motor function using the Hammersmith Functional Motor Scale and other functional tests for motor function and pulmonary function. Somatropin treatment did not significantly affect upper limb muscle strength (point estimate mean: 0.08 N, 95% confidence interval (CI:-3.79;3.95, p = 0.965), lower limb muscle strength (point estimate mean: 2.23 N, CI:-2.19;6.63, p = 0.302) or muscle and pulmonary function. Side effects occurring during somatropin treatment corresponded with well-known side effects of growth hormone substitution in patients with growth hormone deficiency. In this pilot study, growth hormone treatment did not improve muscle strength or function in patients with spinal muscular atrophy type II/III.
authors.affiliation: Department of Neuropaediatrics and Muscle Disorders, University Medical Center, Freiburg, Germany. Electronic address: janbernd.kirschner@uniklinik-freiburg.de.
authors.forename: J
authors.initials: J
authors.lastname: Kirschner
authors.affiliation: Department of Neuropaediatrics and Muscle Disorders, University Medical Center, Freiburg, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Schorling
authors.affiliation: Institute of Medical Biometry and Medical Informatics, University of Freiburg, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Hauschke
authors.affiliation: Department of Neuropaediatrics and Muscle Disorders, University Medical Center, Freiburg, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Rensing-Zimmermann
authors.affiliation: Department of Neuropaediatrics and Muscle Disorders, University Medical Center, Freiburg, Germany.
authors.forename: U
authors.initials: U
authors.lastname: Wein
authors.affiliation: Department of Neuropaediatrics, Charité University Medical School, Berlin, Germany.
authors.forename: U
authors.initials: U
authors.lastname: Grieben
authors.affiliation: Department of Neuropaediatrics, Charité University Medical School, Berlin, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Schottmann
authors.affiliation: Department of Paediatric Neurology, University Hospital Essen, Germany.
authors.forename: U
authors.initials: U
authors.lastname: Schara
authors.affiliation: Department of Paediatric Endocinology, University Hospital Essen, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Konrad
authors.affiliation: Department of Paediatric Neurology and Developmental Medicine, Dr. Von Hauner Children's Hospital, München, Germany.
authors.forename: W
authors.initials: W
authors.lastname: Müller-Felber
authors.affiliation: Department of Paediatric Neurology and Developmental Medicine, Dr. Von Hauner Children's Hospital, München, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Thiele
authors.affiliation: Department of Paediatrics and Paediatric Neurology, Georg August University, Göttingen, Germany.
authors.forename: E
authors.initials: E
authors.lastname: Wilichowski
authors.affiliation: Department of Paediatrics and Paediatric Neurology, Georg August University, Göttingen, Germany.
authors.forename: E
authors.initials: E
authors.lastname: Hobbiebrunken
authors.affiliation: Department of Paediatrics and Paediatric Neurology, Georg August University, Göttingen, Germany.
authors.forename: G M
authors.initials: GM
authors.lastname: Stettner
authors.affiliation: Department of Neuropaediatrics and Muscle Disorders, University Medical Center, Freiburg, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Korinthenberg
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D018592:Cross-Over Studies; D004185:Disability Evaluation; D004311:Double-Blind Method; D005260:Female; D020249:Hormone Replacement Therapy / Q000009:adverse effects; D019382:Human Growth Hormone / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D035002:Lower Extremity / Q000503:physiopathology; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D053580:Muscle Strength / Q000187:drug effects; D010865:Pilot Projects; D012129:Respiratory Function Tests; D014897:Spinal Muscular Atrophies of Childhood / Q000188:drug therapy* / Q000503:physiopathology; D016896:Treatment Outcome; D034941:Upper Extremity / Q000503:physiopathology; D055815:Young Adult
chemical_list: D019382:Human Growth Hormone
keywords: Growth hormone; Hand-held myometry; Randomized placebo-controlled trial; Spinal muscular atrophy