Randomized trial of inosine for urate elevation in amyotrophic lateral sclerosis

David Walk, Katharine Nicholson, Eduardo Locatelli, James Chan, Eric A. Macklin, Valerie Ferment, Georgios Manousakis, Marianne Chase, Mariah Connolly, Derek Dagostino, Meghan Hall, Joseph Ostrow, Lindsay Pothier, Cassandra Lieberman, Dario Gelevski, Rebecca Randall, Alexander V. Sherman, Erin Steinhart, Daniela Grasso Walker, Jason WalkerHong Yu, Anne Marie Wills, Michael A. Schwarzschild, Anna L. Beukenhorst, Jukka Pekka Onnela, James D. Berry, Merit E. Cudkowicz, Sabrina Paganoni

Research output: Contribution to journalArticlepeer-review

8 Scopus citations


Introduction/Aims: Higher urate levels are associated with improved ALS survival in retrospective studies, however whether raising urate levels confers a survival advantage is unknown. In the Safety of Urate Elevation in Amyotrophic Lateral Sclerosis (SURE-ALS) trial, inosine raised serum urate and was safe and well-tolerated. The SURE-ALS2 trial was designed to assess longer term safety. Functional outcomes and a smartphone application were also explored. Methods: Participants were randomized 2:1 to inosine (n = 14) or placebo (n = 9) for 20 weeks, titrated to serum urate of 7–8 mg/dL. Primary outcomes were safety and tolerability. Functional outcomes were measured with the Amyotrophic Lateral Sclerosis Functional Rating Scale Revised (ALSFRS-R). Mobility and ALSFRS-R were also assessed by a smartphone application. Results: During inosine treatment, mean urate ranged 5.68–6.82 mg/dL. Treatment-emergent adverse event (TEAE) incidence was similar between groups (p >.10). Renal TEAEs occurred in three (21%) and hypertension in one (7%) of participants randomized to inosine. Inosine was tolerated in 71% of participants versus placebo 67%. Two participants (14%) in the inosine group experienced TEAEs deemed related to treatment (nephrolithiasis); one was a severe adverse event. Mean ALSFRS-R decline did not differ between groups (p =.69). Change in measured home time was similar between groups. Digital and in-clinic ALSFRS-R correlated well. Discussion: Inosine met pre-specified criteria for safety and tolerability. A functional benefit was not demonstrated in this trial designed for safety and tolerability. Findings suggested potential utility for a smartphone application in ALS clinical and research settings.

Original languageEnglish (US)
Pages (from-to)378-386
Number of pages9
JournalMuscle and Nerve
Issue number5
StatePublished - May 2023

Bibliographical note

Funding Information:
The authors thank the individuals who participated in the SURE-ALS2 trial and their caregivers and families; The Salah Foundation; and Data and Safety Monitoring Board members Hyon Choi, MD, David Goldfarb, MD, and Colin Quinn, MD. Lara Primak, MD, of PRECISIONScientia provided medical writing assistance with the development of the manuscript under the direction of the authors, in compliance with international Good Publication Practice guidelines.

Publisher Copyright:
© 2023 The Authors. Muscle & Nerve published by Wiley Periodicals LLC.


  • amyotrophic lateral sclerosis
  • clinical trial
  • inosine
  • oxidative stress
  • smartphone application

PubMed: MeSH publication types

  • Randomized Controlled Trial
  • Journal Article
  • Research Support, Non-U.S. Gov't


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