title: Recombinant insulin-like growth factor (IGF)-I treatment in short children with low IGF-I levels: first-year results from a randomized clinical trial.
abstract: BACKGROUND
  Short stature in children may be associated with low IGF-I despite normal stimulated GH levels and without other causes.
  
  
  OBJECTIVE
  Our objective was to assess the safety and efficacy of recombinant human IGF-I (rhIGF-I) in short children with low IGF-I levels.
  
  
  METHODS
  This was a 1-yr, randomized, open-label trial (MS301).
  
  
  METHODS
  The study was conducted at 30 U.S. pediatric endocrinology clinics.
  
  
  METHODS
  A total of 136 short, prepubertal subjects with low IGF-I (height and IGF-I sd scores <-2, stimulated GH > or =7 ng/ml); 124 completed the study, and six withdrew for adverse events and six for other reasons.
  
  
  METHODS
  rhIGF-I was administered sc, twice daily using weight-based dosing (40, 80, or 120 microg/kg; n = 111) or subjects were observed (n = 25).
  
  
  METHODS
  First-year height velocity (centimeters per year, cm/yr), height sd score, IGF-I, and adverse events were prespecified outcomes.
  
  
  RESULTS
  First-year height velocities for subjects completing the trial were increased for the 80- and 120-microg/kg twice-daily vs. the untreated group (7.0 +/- 1.0, 7.9 +/- 1.4, and 5.2 +/- 1.0 cm/yr, respectively; all P < 0.0001) and for the 120- vs. 80-microg/kg group (P = 0.0002) and were inversely related to age. They were not predicted by GH stimulation or IGF-I generation test results and were not correlated with IGF-I antibody status. The most commonly reported adverse events of special interest during treatment were headache (38% of subjects), vomiting (25%), and hypoglycemia (14%).
  
  
  CONCLUSIONS
  rhIGF-I treatment was associated with age- and dose-dependent increases in first-year height velocity. Adverse events during treatment were less common than in previous studies and were generally transient, easily managed, and without known sequelae.
authors.affiliation: Tercica, Inc., a subsidiary of the Ipsen Group, 2000 Sierra Point Parkway, Suite 400, Brisbane, California 94005, USA.
authors.forename: L Kurt
authors.initials: LK
authors.lastname: Midyett
authors.forename: Alan D
authors.initials: AD
authors.lastname: Rogol
authors.forename: Quentin L
authors.initials: QL
authors.lastname: Van Meter
authors.forename: James
authors.initials: J
authors.lastname: Frane
authors.forename: George M
authors.initials: GM
authors.lastname: Bright
mesh_terms: D000365:Age Determination by Skeleton; D001827:Body Height / Q000187:drug effects; D015992:Body Mass Index; D002648:Child; D002675:Child, Preschool; D005260:Female; D006130:Growth Disorders / Q000188:drug therapy*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000009:adverse effects / Q000032:analysis / Q000172:deficiency* / Q000627:therapeutic use*; D008297:Male; D011627:Puberty; D011994:Recombinant Proteins / Q000627:therapeutic use
chemical_list: D011994:Recombinant Proteins; D007334:Insulin-Like Growth Factor I