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 > or =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 microg/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-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.
RCT Entities:
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 humanIGF-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 > or =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 microg/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-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: Helen L Storr; Sumana Chatterjee; Louise A Metherell; Corinne Foley; Ron G Rosenfeld; Philippe F Backeljauw; Andrew Dauber; Martin O Savage; Vivian Hwa Journal: Endocr Rev Date: 2019-04-01 Impact factor: 19.871
Authors: Wayne V Moore; Huong Jil Nguyen; Gad B Kletter; Bradley S Miller; Douglas Rogers; David Ng; Jerome A Moore; Eric Humphriss; Jeffrey L Cleland; George M Bright Journal: J Clin Endocrinol Metab Date: 2015-12-16 Impact factor: 5.958