Effect of recombinant human insulin-like growth factor-I on progression of ALS. A placebo-controlled study. The North America ALS/IGF-I Study Group.
The objective of this study was to investigate the safety and efficacy of recombinant human insulinlike growth factor-I (rhIGF-I) in the treatment 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 administered for 9 months. The primary outcome measure was disease symptom progression, assessed by the rate of change (per patient slope) in the Appel ALS rating scale total score. The Sickness Impact Profile (SIP), a patient-perceived, health-related quality of life assessment, was a secondary outcome variable. Progression of functional impairment in patients receiving high-dose (0.10 mg/kg/day) rhIGF-I was 26% slower than in patients receiving placebo (p = 0.01). The high-dose treatment group was less likely to terminate the study due to protocol-defined markers 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 response. The incidence of clinically significant adverse experiences was comparable among the three treatment groups. Recombinant human insulin-like growth factor-I slowed the progression of functional impairment and the decline in health-related quality of life in patients with ALS with no medically important adverse effects.
Lai
E C
EC
Department of Neurology, Baylor College of Medicine, Houston, TX 77030, USA.
Felice
K J
KJ
Festoff
B W
BW
Gawel
M J
MJ
Gelinas
D F
DF
Kratz
R
R
Murphy
M F
MF
Natter
H M
HM
Norris
F H
FH
Rudnicki
S A
SA
D000690:Amyotrophic Lateral Sclerosis / Q000503:physiopathology* / Q000628:therapy*; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010919:Placebos; D011994:Recombinant Proteins; D012720:Severity of Illness Index; D018434:Sickness Impact Profile; D016019:Survival Analysis; D016896:Treatment Outcome
D010919:Placebos; D011994:Recombinant Proteins; D007334:Insulin-Like Growth Factor I