Clinical trials in amyotrophic lateral sclerosis: Why so many negative trials and how can trials be improved?

Hiroshi Mitsumoto, Benjamin R. Brooks, Vincenzo Silani

Research output: Contribution to journalArticlepeer-review

Abstract

Amyotrophic lateral sclerosis (ALS) is one of the most rapidly progressive neurodegenerative diseases of unknown cause. Riluzole is the only drug that slows disease progression. More than 50 randomised controlled trials (RCTs) of proposed disease-modifying drugs have failed to show positive results in the past half-century. In the past decade, at least 18 drugs have been tested in large phase 2 or 3 RCTs, including lithium, which was tested in several RCTs. Potential reasons for the negative results can be classified into three categories: first, issues regarding trial rationale and preclinical study results; second, pharmacological issues; and third, clinical trial design and methodology issues. Clinical trials for stem cell therapy and RCTs targeting pharmacological or non-pharmacological symptomatic treatment in ALS are examples of areas that need novel design strategies. Only through critical analyses of the failed trials can new and important suggestions be identified for the future success of clinical trials in ALS.

Original languageEnglish
Pages (from-to)1127-1138
Number of pages12
JournalThe Lancet Neurology
Volume13
Issue number11
DOIs
Publication statusPublished - Nov 1 2014

ASJC Scopus subject areas

  • Clinical Neurology
  • Medicine(all)

Fingerprint Dive into the research topics of 'Clinical trials in amyotrophic lateral sclerosis: Why so many negative trials and how can trials be improved?'. Together they form a unique fingerprint.

Cite this