Can selection of rapidly progressing patients shorten clinical trials in amyotrophic lateral sclerosis?
BACKGROUND
The marked variability in progression of amyotrophic lateral sclerosis (ALS) requires large numbers of patients to detect a significant effect in current clinical trial designs.


OBJECTIVE
To test the utility of a lead-in period to assess rate of progression so that patients with rapidly progressive ALS can be selected for subsequent clinical trials.


METHODS
Prospective study.


METHODS
The ALS Center, University of Lisbon, Lisbon, Portugal.


METHODS
Fifty-seven consecutively recruited patients assessed at diagnosis and 3 months later (end of lead-in period).


METHODS
Change in ALS Functional Rating Scale (ALS-FRS) score was analyzed to establish a statistically significant cutoff point to define patients with rapid (group 1) or slow (group 2) progression. Patients from both groups were reexamined 1 and 3 months after the lead-in period.


METHODS
Changes in ALS-FRS score, motor unit number estimation, and neurophysiologic index, and resultant grouping of patients according to rate of progression at 1 and 3 months.


RESULTS
Both the 80th percentile and 2 SDs above the mean of the change in ALS-FRS score identified the same patients. Twelve patients showed rapid progression (group 1) and 45 showed slow progression (group 2). One month after the lead-in period there was a significant reduction in ALS-FRS score, motor unit number estimation, and neurophysiologic index in group 1, and after 3 months all these measurements changed significantly in both groups.


CONCLUSIONS
This strategy of selecting patients with rapidly progressing ALS for inclusion in exploratory, short phase II clinical trials offers substantial savings in costs and time, and could accelerate the process of testing potentially useful drugs for the treatment of ALS.
de Carvalho
Mamede
M
Department of Neurology, Hospital de Santa Maria, Lisbon, Portugal.
Swash
Michael
M
D000328:Adult; D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000175:diagnosis* / Q000188:drug therapy* / Q000503:physiopathology; D002986:Clinical Trials as Topic / Q000379:methods* / Q000592:standards; D004185:Disability Evaluation; D018450:Disease Progression; D004568:Electrodiagnosis; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009431:Neural Conduction / Q000502:physiology; D018579:Patient Selection; D010525:Peripheral Nerves / Q000503:physiopathology; D011237:Predictive Value of Tests; D011446:Prospective Studies; D013997:Time Factors