Clemastine fumarate as a remyelinating therapy for multiple sclerosis (ReBUILD): a randomised, controlled, double-blind, crossover trial

Ari J. Green*, Jeffrey M. Gelfand, Bruce A. Cree, Carolyn Bevan, W. John Boscardin, Feng Mei, Justin Inman, Sam Arnow, Michael Devereux, Aya Abounasr, Hiroko Nobuta, Alyssa Zhu, Matt Friessen, Roy Gerona, Hans Christian von Büdingen, Roland G. Henry, Stephen L. Hauser, Jonah R. Chan

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

134 Scopus citations

Abstract

Background Multiple sclerosis is a degenerative inflammatory disease of the CNS characterised by immune-mediated destruction of myelin and progressive neuroaxonal loss. Myelin in the CNS is a specialised extension of the oligodendrocyte plasma membrane and clemastine fumarate can stimulate differentiation of oligodendrocyte precursor cells in vitro, in animal models, and in human cells. We aimed to analyse the efficacy and safety of clemastine fumarate as a treatment for patients with multiple sclerosis. Methods We did this single-centre, 150-day, double-blind, randomised, placebo-controlled, crossover trial (ReBUILD) in patients with relapsing multiple sclerosis with chronic demyelinating optic neuropathy on stable immunomodulatory therapy. Patients who fulfilled international panel criteria for diagnosis with disease duration of less than 15 years were eligible. Patients were randomly assigned (1:1) via block randomisation using a random number generator to receive either clemastine fumarate (5·36 mg orally twice daily) for 90 days followed by placebo for 60 days (group 1), or placebo for 90 days followed by clemastine fumarate (5·36 mg orally twice daily) for 60 days (group 2). The primary outcome was shortening of P100 latency delay on full-field, pattern-reversal, visual-evoked potentials. We analysed by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT02040298. Findings Between Jan 1, 2014, and April 11, 2015, we randomly assigned 50 patients to group 1 (n=25) or group 2 (n=25). All patients completed the study. The primary efficacy endpoint was met with clemastine fumarate treatment, which reduced the latency delay by 1·7 ms/eye (95% CI 0·5–2·9; p=0·0048) when analysing the trial as a crossover. Clemastine fumarate treatment was associated with fatigue, but no serious adverse events were reported. Interpretation To our knowledge, this is the first randomised controlled trial to document efficacy of a remyelinating drug for the treatment of chronic demyelinating injury in multiple sclerosis. Our findings suggest that myelin repair can be achieved even following prolonged damage. Funding University of California, San Francisco and the Rachleff Family.

Original languageEnglish (US)
Pages (from-to)2481-2489
Number of pages9
JournalThe Lancet
Volume390
Issue number10111
DOIs
StatePublished - Dec 2 2017

ASJC Scopus subject areas

  • Medicine(all)

Fingerprint Dive into the research topics of 'Clemastine fumarate as a remyelinating therapy for multiple sclerosis (ReBUILD): a randomised, controlled, double-blind, crossover trial'. Together they form a unique fingerprint.

Cite this