Phase III randomized trial of gabapentin in patients with amyotrophic lateral sclerosis.
BACKGROUND
Preclinical and clinical studies of gabapentin in patients with ALS led the authors to undertake a phase III randomized clinical trial.


METHODS
Patients were randomly assigned, in a double-blinded fashion, to receive oral gabapentin 3,600 mg or placebo daily for 9 months. The primary outcome measure was the average rate of decline in isometric arm muscle strength for those with two or more evaluations.


RESULTS
Two hundred four patients enrolled, 196 had two or more evaluations, and 128 patients completed the study. The mean rate of decline of the arm muscle strength was not significantly different between the groups. Moreover, there was no beneficial effect upon the rate of decline of other secondary measures (vital capacity, survival, ALS functional rating scale, timed walking) nor was there any symptomatic benefit. In fact, analysis of the combined data from the phase II and III trials revealed a significantly more rapid decline of forced vital capacity in patients treated with gabapentin.


CONCLUSIONS
These data provide no evidence of a beneficial effect of gabapentin on disease progression or symptoms in patients with ALS.
Miller
R G
RG
Department of Neurology, California Pacific Medical Center, San Francisco, USA. rmiller@cooper.cpmc.org
Moore
D H
DH
Gelinas
D F
DF
Dronsky
V
V
Mendoza
M
M
Barohn
R J
RJ
Bryan
W
W
Ravits
J
J
Yuen
E
E
Neville
H
H
Ringel
S
S
Bromberg
M
M
Petajan
J
J
Amato
A A
AA
Jackson
C
C
Johnson
W
W
Mandler
R
R
Bosch
P
P
Smith
B
B
Graves
M
M
Ross
M
M
Sorenson
E J
EJ
Kelkar
P
P
Parry
G
G
Olney
R
R
D000085:Acetates / Q000008:administration & dosage* / Q000009:adverse effects*; D000588:Amines; D000690:Amyotrophic Lateral Sclerosis / Q000188:drug therapy* / Q000401:mortality; D003509:Cyclohexanecarboxylic Acids; D004311:Double-Blind Method; D005260:Female; D000077206:Gabapentin; D006801:Humans; D008297:Male; D008875:Middle Aged; D018401:Sample Size; D016019:Survival Analysis; D005680:gamma-Aminobutyric Acid
D000085:Acetates; D000588:Amines; D003509:Cyclohexanecarboxylic Acids; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin