Journal article
Trial of Sodium Phenylbutyrate-Taurursodiol for Amyotrophic Lateral Sclerosis
The New England journal of medicine, Vol.383(10), pp.919-930
09/03/2020
DOI: 10.1056/NEJMoa1916945
PMCID: PMC9134321
PMID: 32877582
Abstract
Sodium 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.
In 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.
A 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.
Sodium 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.).
Details
- Title: Subtitle
- Trial of Sodium Phenylbutyrate-Taurursodiol for Amyotrophic Lateral Sclerosis
- Creators
- Sabrina Paganoni - Harvard UniversityEric A Macklin - Harvard UniversitySuzanne HendrixJames D Berry - Harvard UniversityMichael A ElliottSamuel MaiserChafic Karam - Oregon Health & Science UniversityJames B Caress - Wake Forest UniversityMargaret A Owegi - University of Massachusetts Medical SchoolAdam Quick - The Ohio State UniversityJames Wymer - University of FloridaStephen A Goutman - University of Michigan–Ann ArborDaragh HeitzmanTerry Heiman-Patterson - Temple UniversityCarlayne E Jackson - Spaulding Rehabilitation HospitalColin Quinn - University of PennsylvaniaJeffrey D Rothstein - Spaulding Rehabilitation HospitalEdward J Kasarskis - University of KentuckyJonathan Katz - California Pacific Medical CenterLiberty Jenkins - California Pacific Medical CenterShafeeq Ladha - St. Joseph's Hospital and Medical CenterTimothy M Miller - Washington University in St. LouisStephen N Scelsa - Icahn School of Medicine at Mount SinaiTuan H Vu - University of South FloridaChristina N Fournier - Emory UniversityJonathan D Glass - Emory UniversityKristin M Johnson - Ochsner Health SystemAndrea Swenson - University of IowaNamita A Goyal - University of California, IrvineGary L PatteePatricia L AndresSuma Babu - Harvard UniversityMarianne Chase - Harvard UniversityDerek Dagostino - Harvard UniversitySamuel P DicksonNoel EllisonMeghan Hall - St. Joseph's Hospital and Medical CenterKent HendrixGale Kittle - St. Joseph's Hospital and Medical CenterMichelle McGovern - Harvard UniversityJoseph Ostrow - Harvard UniversityLindsay Pothier - Harvard UniversityRebecca Randall - St. Joseph's Hospital and Medical CenterJeremy M Shefner - St. Joseph's Hospital and Medical CenterAlexander V Sherman - Harvard UniversityEric Tustison - Harvard UniversityPrasha Vigneswaran - Harvard UniversityJason Walker - Harvard UniversityHong Yu - Harvard UniversityJames Chan - Harvard UniversityJanet WittesJoshua CohenJustin KleeKent LeslieRudolph E Tanzi - Harvard UniversityWalter Gilbert - Harvard UniversityPatrick D YeramianDavid Schoenfeld - Harvard UniversityMerit E Cudkowicz - Harvard University
- Resource Type
- Journal article
- Publication Details
- The New England journal of medicine, Vol.383(10), pp.919-930
- DOI
- 10.1056/NEJMoa1916945
- PMID
- 32877582
- PMCID
- PMC9134321
- NLM abbreviation
- N Engl J Med
- ISSN
- 0028-4793
- eISSN
- 1533-4406
- Grant note
- S10 OD020007 / NIH HHS
- Language
- English
- Date published
- 09/03/2020
- Academic Unit
- Neurology
- Record Identifier
- 9984303019002771
Metrics
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