INTRAVENOUS INSULIN-LIKE GROWTH-FACTOR-I (IGF-I) IN MODERATE-TO-SEVERE HEAD-INJURY - A PHASE-II SAFETY AND EFFICACY TRIAL

The purpose of this study was to determine the effect of insulin-like growth factor-I (IGF-I) on the catabolic state and clinical outcome of head-injured patients. Thirty-three patients between the ages of 18 a nd 59 years with isolated traumatic head injury and Glasgow Coma Scale (GCS) scores of 4 to 10 were randomized to one of two groups. All pat ients received standard neurosurgical intensive care plus aggressive n utritional support. the patients in the treatment group also received intravenous therapy with continuous IGF-I (0.01 mg/kg/hour). During th e 14-day dosing period, the control patients lost weight, whereas trea ted patients gained weight despite a significantly higher measured ene rgy expenditure and lower caloric intake (p = 0.02). Daily glucose con centrations and nitrogen outputs were greater in control patients (p = 0.03) throughout the study period. During Week 1, only treated patien ts achieved positive nitrogen balance. Fifteen of 17 treated and 13 of 16 control patients survived the Ist week. No deaths occurred in pati ents whose serum IGF-I concentrations were higher than 350 ng/ml. Dich otomized Glasgow Outcome Scale scores for patients with baseline GCS s cores of 5 to 7 improved from poor to good for eight of 12 treated pat ients but for only three of 11 control patients (p = 0.06). Eight of 1 1 treated patients with serum IGF-I concentrations that were at least 350 ng/ml achieved moderate-to-good outcome scores at 6 months, compar ed to only one of five patients with lower concentrations (p < 0.05). These findings indicate that pharmacological concentrations of IGF-I m ay improve clinical outcome and nitrogen utilization in patients with moderate-to-severe head injury.