Recombinant Insulin-Like Growth Factor (IGF)-I Treatment in Short Children with Low IGF-I Levels: First-Year Results from a Randomized Clinical Trial

Context: 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. Design: This was a 1-yr, randomized, open-label trial (MS301). Setting: The study was conducted at 30 U. S. pediatric endocrinology clinics. Subjects: A total of 136 short, prepubertal subjects with low IGF-I ( height and IGF-I SD scores <-2, stimulated GH >= 7 ng/ml); 124 completed the study, and six withdrew for adverse events and six for other reasons. Intervention: rhIGF-I was administered sc, twice daily using weight-based dosing (40, 80, or 120 mu g/kg; n = 111) or subjects were observed (n = 25). Main Outcome Measures: 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-mu g/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-mu g/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. (J Clin Endocrinol Metab 95: 611-619, 2010)