A randomized controlled clinical trial of growth hormone in amyotrophic lateral sclerosis: clinical, neuroimaging, and hormonal results

J Neurol. 2012 Jan;259(1):132-8. doi: 10.1007/s00415-011-6146-2. Epub 2011 Jun 25.


Amyotrophic lateral sclerosis (ALS) is a fatal neurological disease with motor neuron degeneration. Riluzole is the only available treatment. Two-thirds of ALS patients present with growth hormone (GH) deficiency. The aim of this study is to determine if add-on of GH to riluzole, with an individually regulated dose based on Insulin-like growth factor 1 (IGF-I) production, was able to reduce neuronal loss in the motor cortex, reduce mortality, and improve motor function of ALS patients. Patients with definite/probable ALS, in treatment with riluzole, aged 40-85 years, and with disease duration ≤3 years were enrolled. The study was randomized, placebo controlled, and double blind. Before treatment, patients were tested with a GH releasing hormone (GHRH) + arginine test. The initial dose of GH was 2 IU s.c. every other day, and was progressively increased to a maximum of 8 IU. Primary endpoint was N-acetylaspartate/(creatine + choline) (NAA/Cre + Cho) ratio in motor cortex assessed by magnetic resonance spectroscopy performed at months 0, 6, and 12. Secondary endpoints were mortality and ALS functional rating scale revised (ALSFRS-R). The NAA/(Cre + Cho) ratio decreased in all patients who completed the trial. No significant difference was noted between treated and placebo group. At baseline, although IGF-I levels were within the normal range, 73% of patients had GH deficiency, being severe in half of them. Compared with bulbar onset, spinal-onset patients showed more depressed GH response to the GHRH + arginine stimulation test (10.4 ± 7.0 versus 15.5 ± 8.1 ng/mL; p < 0.05). Insulin resistance [homeostasis model assessment of insulin resistance (HOMA-IR)] increased from 2.1 ± 1.0 at baseline to 4.6 ± 1.9 at 12 months (p < 0.001). Insulin-like growth factor (IGF) binding protein 3 (IGFBP-3) decreased from 8,435 ± 4,477 ng/mL at baseline to 3,250 ± 1,780 ng/mL at 12 months (p < 0.001). The results show that GH exerted no effect on cerebral NAA or clinical progression assessed by ALSFRS-R. Two-thirds of ALS patients had GH deficit, with higher levels in the bulbar-onset group. During follow-up, patients showed progressive increase in HOMA-IR and decrease in IGFBP-3 levels.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Amyotrophic Lateral Sclerosis / drug therapy*
  • Amyotrophic Lateral Sclerosis / metabolism
  • Amyotrophic Lateral Sclerosis / pathology
  • Arginine
  • Choline / blood
  • Creatine / blood
  • Double-Blind Method
  • Endpoint Determination
  • Female
  • Hormones / blood*
  • Human Growth Hormone / blood
  • Human Growth Hormone / therapeutic use*
  • Humans
  • Image Processing, Computer-Assisted
  • Insulin Resistance
  • Insulin-Like Growth Factor Binding Protein 3 / blood
  • Insulin-Like Growth Factor I / analysis
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Motor Cortex / pathology
  • Neuroimaging
  • Neuroprotective Agents / therapeutic use
  • Recombinant Proteins / therapeutic use
  • Riluzole / therapeutic use


  • Hormones
  • Insulin-Like Growth Factor Binding Protein 3
  • Neuroprotective Agents
  • Recombinant Proteins
  • Human Growth Hormone
  • Insulin-Like Growth Factor I
  • Riluzole
  • Arginine
  • Creatine
  • Choline