umu.sePublications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Randomized, double-blind, placebo-controlled trial of arimoclomol in rapidly progressive SOD1 ALS
Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience.
Show others and affiliations
2018 (English)In: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 90, no 7, p. E565-E574Article in journal (Refereed) Published
Abstract [en]

ObjectiveTo examine the safety and tolerability as well as the preliminary efficacy of arimoclomol, a heat shock protein co-inducer that promotes nascent protein folding, in patients with rapidly progressive SOD1 amyotrophic lateral sclerosis (ALS).

MethodsThis was a double-blind, placebo-controlled trial in which patients with rapidly progressive SOD1-mutant ALS were randomized 1:1 to receive arimoclomol 200 mg tid or matching placebo for up to 12 months. Study procedures were performed using a mix of in-person and remote assessments. Primary outcome was safety and tolerability. Secondary outcome was efficacy, with survival as the principal measure. Additional efficacy measures were the rates of decline of the Revised ALS Functional Rating Scale (ALSFRS-R) and percent predicted forced expiratory volume in 6 seconds (FEV6), and the Combined Assessment of Function and Survival (CAFS).

ResultsThirty-eight participants were randomized. Thirty-six (19 placebo, 17 arimoclomol) were included in the prespecified intent-to-treat analysis. Apart from respiratory function, groups were generally well-balanced at baseline. Adverse events occurred infrequently, and were usually mild and deemed unlikely or not related to study drug. Adjusting for riluzole and baseline ALSFRS-R, survival favored arimoclomol with a hazard ratio of 0.77 (95% confidence interval [CI] 0.32-1.80). ALSFRS-R and FEV6 declined more slowly in the arimoclomol group, with treatment differences of 0.5 point/month (95% CI -0.63 to 1.63) and 1.24 percent predicted/month (95% CI -2.77 to 5.25), respectively, and the CAFS similarly favored arimoclomol.

ConclusionsThis study provides Class II evidence that arimoclomol is safe and well-tolerated at a dosage of 200 mg tid for up to 12 months. Although not powered for therapeutic effect, the consistency of results across the range of prespecified efficacy outcome measures suggests a possible therapeutic benefit of arimoclomol.

Clinicaltrials.gov identifierNCT00706147.

Classification of evidenceThis study provides Class II evidence that arimoclomol is safe and well-tolerated at a dosage of 200 mg tid for up to 12 months. The study lacked the precision to conclude, or to exclude, an important therapeutic benefit of arimoclomol.

Place, publisher, year, edition, pages
Lippincott Williams & Wilkins, 2018. Vol. 90, no 7, p. E565-E574
National Category
Neurology
Identifiers
URN: urn:nbn:se:umu:diva-146584DOI: 10.1212/WNL.0000000000004960ISI: 000427813200004PubMedID: 29367439OAI: oai:DiVA.org:umu-146584DiVA, id: diva2:1198477
Available from: 2018-04-17 Created: 2018-04-17 Last updated: 2018-06-09Bibliographically approved

Open Access in DiVA

fulltext(505 kB)14 downloads
File information
File name FULLTEXT01.pdfFile size 505 kBChecksum SHA-512
a380a3355f76c07782b77412c6c7cfcfa6f283b478111b53bd0d3a608ef7f60b4c84084ad2f4c959f16d1f81af12b755eb3fcbafa09e2ec8705fed7a4fc0fffb
Type fulltextMimetype application/pdf

Other links

Publisher's full textPubMed

Authority records BETA

Andersen, Peter M.

Search in DiVA

By author/editor
Andersen, Peter M.
By organisation
Department of Pharmacology and Clinical Neuroscience
In the same journal
Neurology
Neurology

Search outside of DiVA

GoogleGoogle Scholar
Total: 14 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 141 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf