EFFECT OF RECOMBINANT HUMAN INSULIN-LIKE GROWTH-FACTOR-I ON PROGRESSION OF ALS - A PLACEBO-CONTROLLED STUDY

The objective of this study was to investigate the safety and efficacy of recombinant human insulinlike growth factor-I (rhIGF-I) in the tre atment of sporadic ALS. A double-blind, placebo-controlled, randomized study of 266 patients was conducted at eight centers in North America . Placebo or rhIGF-I (0.05 mg/kg/day or 0.10 mg/kg/day) was administer ed for 9 months. The primary outcome measure was disease symptom progr ession, assessed by the rate of change (per patient slope) in the Appe l ALS rating scale total score. The Sickness Impact Profile (STP), a p atient-perceived, health-related quality of life assessment, was a sec ondary outcome variable. Progression of functional impairment in patie nts receiving high-dose (0.10 mg/kg/day) rhIGF-I was 26% slower than i n patients receiving placebo (p = 0.01). The high-dose treatment group was less likely to terminate the study due to protocol-defined marker s of disease symptom progression, and members in this group exhibited a slower decline in quality of life, as assessed by the SIP. Patients receiving 0.05 mg/kg/day of rhIGF-I exhibited trends similar to those associated with high-dose treatment, suggesting a dose-dependent respo nse. The incidence of clinically significant adverse experiences was c omparable among the three treatment groups. Recombinant human insulin- like growth factor-I slowed the progression of functional impairment a nd the decline in health-related quality of life in patients with ALS with no medically important adverse effects.