학술논문
Trial of Sodium Phenylbutyrate–Taurursodiol for Amyotrophic Lateral Sclerosis
Document Type
article
Author
Paganoni, Sabrina; Macklin, Eric A; Hendrix, Suzanne; Berry, James D; Elliott, Michael A; Maiser, Samuel; Karam, Chafic; Caress, James B; Owegi, Margaret A; Quick, Adam; Wymer, James; Goutman, Stephen A; Heitzman, Daragh; Heiman-Patterson, Terry; Jackson, Carlayne E; Quinn, Colin; Rothstein, Jeffrey D; Kasarskis, Edward J; Katz, Jonathan; Jenkins, Liberty; Ladha, Shafeeq; Miller, Timothy M; Scelsa, Stephen N; Vu, Tuan H; Fournier, Christina N; Glass, Jonathan D; Johnson, Kristin M; Swenson, Andrea; Goyal, Namita A; Pattee, Gary L; Andres, Patricia L; Babu, Suma; Chase, Marianne; Dagostino, Derek; Dickson, Samuel P; Ellison, Noel; Hall, Meghan; Hendrix, Kent; Kittle, Gale; McGovern, Michelle; Ostrow, Joseph; Pothier, Lindsay; Randall, Rebecca; Shefner, Jeremy M; Sherman, Alexander V; Tustison, Eric; Vigneswaran, Prasha; Walker, Jason; Yu, Hong; Chan, James; Wittes, Janet; Cohen, Joshua; Klee, Justin; Leslie, Kent; Tanzi, Rudolph E; Gilbert, Walter; Yeramian, Patrick D; Schoenfeld, David; Cudkowicz, Merit E
Source
New England Journal of Medicine. 383(10)
Subject
Language
Abstract
BackgroundSodium phenylbutyrate and taurursodiol have been found to reduce neuronal death in experimental models. The efficacy and safety of a combination of the two compounds in persons with amyotrophic lateral sclerosis (ALS) are not known.MethodsIn this multicenter, randomized, double-blind trial, we enrolled participants with definite ALS who had had an onset of symptoms within the previous 18 months. Participants were randomly assigned in a 2:1 ratio to receive sodium phenylbutyrate-taurursodiol (3 g of sodium phenylbutyrate and 1 g of taurursodiol, administered once a day for 3 weeks and then twice a day) or placebo. The primary outcome was the rate of decline in the total score on the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R; range, 0 to 48, with higher scores indicating better function) through 24 weeks. Secondary outcomes were the rates of decline in isometric muscle strength, plasma phosphorylated axonal neurofilament H subunit levels, and the slow vital capacity; the time to death, tracheostomy, or permanent ventilation; and the time to death, tracheostomy, permanent ventilation, or hospitalization.ResultsA total of 177 persons with ALS were screened for eligibility, and 137 were randomly assigned to receive sodium phenylbutyrate-taurursodiol (89 participants) or placebo (48 participants). In a modified intention-to-treat analysis, the mean rate of change in the ALSFRS-R score was -1.24 points per month with the active drug and -1.66 points per month with placebo (difference, 0.42 points per month; 95% confidence interval, 0.03 to 0.81; P = 0.03). Secondary outcomes did not differ significantly between the two groups. Adverse events with the active drug were mainly gastrointestinal.ConclusionsSodium phenylbutyrate-taurursodiol resulted in slower functional decline than placebo as measured by the ALSFRS-R score over a period of 24 weeks. Secondary outcomes were not significantly different between the two groups. Longer and larger trials are necessary to evaluate the efficacy and safety of sodium phenylbutyrate-taurursodiol in persons with ALS. (Funded by Amylyx Pharmaceuticals and others; CENTAUR ClinicalTrials.gov number, NCT03127514.).