Somatropin treatment of spinal muscular atrophy: A placebo-controlled, double-blind crossover pilot study

• Published in: Neuromuscular disorders : NMD Vol. 24; no. 2; pp. 134 - 142
• Main Authors: Kirschner, J, Schorling, D, Hauschke, D, Rensing-Zimmermann, C, Wein, U, Grieben, U, Schottmann, G, Schara, U, Konrad, K, Müller-Felber, W, Thiele, S, Wilichowski, E, Hobbiebrunken, E, Stettner, G.M, Korinthenberg, R
• Format: Journal Article
• Language: English
• Published: England Elsevier B.V 01-02-2014
• Subjects: Adolescent; Adult; Child; Cross-Over Studies; Disability Evaluation; Double-Blind Method; Female; Growth hormone; Hand-held myometry; Hormone Replacement Therapy - adverse effects; Human Growth Hormone - adverse effects; Human Growth Hormone - therapeutic use; Humans; Lower Extremity - physiopathology; Male; Motor Activity - drug effects; Muscle Strength - drug effects; Neurology; Pilot Projects; Randomized placebo-controlled trial; Respiratory Function Tests; Spinal Muscular Atrophies of Childhood - drug therapy; Spinal Muscular Atrophies of Childhood - physiopathology; Spinal muscular atrophy; Treatment Outcome; Upper Extremity - physiopathology; Young Adult; Randomized placebo-controlled trial; Growth hormone; Hand-held myometry; Spinal muscular atrophy
• ISSN: 0960-8966; 1873-2364
• DOI: 10.1016/j.nmd.2013.10.011

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.