A placebo-controlled trial of recombinant human ciliary neurotrophic (rhCNTF) factor in amyotrophic lateral sclerosis. rhCNTF ALS Study Group.
Preclinical investigations indicated that recombinant human ciliary neurotrophic factor (rhCNTF) may have potential as therapy for amyotrophic lateral sclerosis (ALS). We evaluated the safety and efficacy of rhCNTF in a prospective, double-blind, placebo-controlled trial in 570 patients with ALS. Patients were randomized to receive 0.5, 2, or 5 micrograms/kg/day rhCNTF, or placebo, for 6 months. The primary efficacy end point was the change from baseline to the last on-treatment value of a combination megascore for limb strength (maximum voluntary isometric contraction) and pulmonary function. Secondary end points included individual arm and leg megascores, pulmonary function tests, an activities-of-daily-living outcome measure, and survival. The four treatment groups were similar at baseline with respect to age, sex, disease duration, and muscle strength values. At all doses tested, rhCNTF had no beneficial effect on the primary or secondary end points. Certain adverse events, as follows, appeared to be dose related: injection site reactions, cough, asthenia, nausea, anorexia, weight loss, and increased salivation. There was an increased number of deaths at the highest dose level. rhCNTF had no beneficial effect on any measure of ALS progression. There were increased adverse events in the 5 micrograms/kg group and increased deaths.
Miller
R G
RG
Department of Neurology, California Pacific Medical Center, San Francisco, CA 94115, USA.
Petajan
J H
JH
Bryan
W W
WW
Armon
C
C
Barohn
R J
RJ
Goodpasture
J C
JC
Hoagland
R J
RJ
Parry
G J
GJ
Ross
M A
MA
Stromatt
S C
SC
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000690:Amyotrophic Lateral Sclerosis / Q000188:drug therapy*; D020934:Ciliary Neurotrophic Factor; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D006801:Humans; D008875:Middle Aged; D009414:Nerve Growth Factors / Q000627:therapeutic use; D009419:Nerve Tissue Proteins / Q000009:adverse effects / Q000627:therapeutic use*; D011446:Prospective Studies; D011994:Recombinant Proteins; D016019:Survival Analysis
D020934:Ciliary Neurotrophic Factor; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D011994:Recombinant Proteins