Evidence map›Paper›PMID 29029896›Full record

Trial reportLancet (London, England)2017

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 and 8 more

6 registry-linked trialsOpen access · bronzeAbstract readRandomized Controlled Trial
PubMed Publisher
In one paragraph

Trial report in Lancet (London, England), 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 6 registered trials, which are not on this map. Cited by 332 papers.

0numbers the graph read from it
0cells of the map it votes in
332citing papers in PubMed
32.0field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT02040298 phase2completednot on this map

A Phase II Randomized, Double-Blind, Parallel-Group, Placebo Controlled Crossover Trial to Assess the Efficacy, Safety, Tolerability, and Pharmacokinetics of Clemastine Fumarate as a Remyelinating Agent in Multiple Sclerosis

TypeinterventionalSponsorUniversity of California, San FranciscoRan2014 to 2016Enrolled50ConditionsMultiple Sclerosis, Relapsing-RemittingArmsClemastine, Placebo
NCT04002934 phase2completednot on this mapstarted 2019, after this paper: background citation

A Phase II Randomized, Double-Blind, Parallel-Group, Placebo Controlled Delayed-Start Trial to Assess the Efficacy, Safety, and Tolerability of Bazedoxifene Acetate (BZA) as a Remyelinating Agent in Patients With Multiple Sclerosis

TypeinterventionalSponsorRiley Bove, MDRan2019 to 2025Enrolled63ConditionsMultiple Sclerosis, Multiple Sclerosis, Relapsing-RemittingArmsBazedoxifene Acetate
NCT05359653 phase1 / phase2recruitingnot on this mapstarted 2023, after this paper: background citation

A Randomized, Double-Blind, Delayed Treatment, Placebo-Controlled Trial to Assess the Changes in Multi-parametric MRI in MS Patients Taking Clemastine Fumarate as a Myelin Repair Therapy

TypeinterventionalSponsorUniversity of California, San FranciscoRan2023 to 2027Enrolled74ConditionsMultiple Sclerosis (MS), Multiple Sclerosis, Relapsing-Remitting, Multiple Sclerosis, Primary Progressive, Multiple Sclerosis, Chronic ProgressiveArmsClemastine Fumarate, Placebo
NCT06065670 phase1 / phase2not yet recruitingnot on this mapstarted 2026, after this paper: background citation

A Randomized, Double-Blind, Delayed Treatment, Placebo-Controlled Trial to Assess the Changes in Multi-parametric MRI in Patients With Acute Demyelinating Lesions Taking Clemastine Fumarate as a Myelin Repair Therapy

TypeinterventionalSponsorUniversity of California, San FranciscoRan2026 to 2028Enrolled44ConditionsDemyelinating Diseases, Demyelination, Corpus Callosum, Multiple Sclerosis Brain LesionArmsClemastine Fumarate, Placebo
NCT06591091 phase2recruitingnot on this mapstarted 2025, after this paper: background citation

Clemastine for Improving White Matter and Boosting Antidepressant Response in Late-life Depression

TypeinterventionalSponsorUniversity of Illinois at ChicagoRan2025 to 2026Enrolled80ConditionsDepressionArmsClemastine Fumarate, Placebo
NCT07304024 phase1 / phase2recruitingnot on this mapstarted 2025, after this paper: background citation

A Double-Blinded, Placebo-Controlled, Randomized, Phase 1/2a Clinical Study to Test the Safety and Efficacy of a Treatment for a Form of Age-Related Central Auditory Processing Disorder Consisting of Clemastine Fumarate Plus Engineered Sound

TypeinterventionalSponsorUniversity of Colorado, DenverRan2025 to 2028Enrolled344ConditionsCentral Auditory Processing Disorder, Hearing Impaired (Partially), Hearing, Hearing AbnormalityArmsClemastine Fumarate Combined With Engineered Sound, Clemastine Fumarate Combined With Pink Noise, Placebo Drug With Engineered Sound, Placebo - Placebo
3 · Its place in the literature

Who cites it

332 citing papers in PubMed, 554 citations in OpenAlex.

  1. Trial
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  5. MWF of the corpus callosum is a robust measure of remyelination: Results from the ReBUILD trial.Proceedings of the National Academy of Sciences of the United States of America · 2023
    Trial
  6. Beyond Histamine Blockade: Clemastine Fumarate as a Promoter of Myelin Regeneration, Inflammatory Regulation, and Neuroimmune Modulation in CNS Disorders.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2026
    Review
  7. Article
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  11. Review
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  13. Stem Cell-Based Therapies for Central Nervous System Demyelinating Diseases: Clinical Evidence, Therapeutic Niches, and Translational Boundaries.Medical science monitor : international medical journal of experimental and clinical research · 2026
    Review
  14. Review
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272 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

18 authors at 2 institutions in 1 country.

Ari J GreenDepartment of Neurology, University of California, San Francisco, San Francisco, CA, USA; Department of Ophthalmology, University of California, San Francisco, San Francisco, CA, USA. Electronic address: agreen@ucsf.edu.
Jeffrey M GelfandDepartment of Neurology, University of California, San Francisco, San Francisco, CA, USA.
Bruce A CreeDepartment of Neurology, University of California, San Francisco, San Francisco, CA, USA.
Carolyn BevanDepartment of Neurology, University of California, San Francisco, San Francisco, CA, USA.
W John BoscardinDepartment of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA, USA.
Feng MeiDepartment of Neurology, University of California, San Francisco, San Francisco, CA, USA; Program in Neuroscience, University of California, San Francisco, San Francisco, CA, USA.
Justin InmanDepartment of Neurology, University of California, San Francisco, San Francisco, CA, USA.
Sam ArnowDepartment of Neurology, University of California, San Francisco, San Francisco, CA, USA.
Michael DevereuxDepartment of Neurology, University of California, San Francisco, San Francisco, CA, USA.
Aya AbounasrDepartment of Neurology, University of California, San Francisco, San Francisco, CA, USA.
Hiroko NobutaDepartment of Pediatrics and Neurosurgery and Eli and Edythe Broad Institute for Stem Cell Research and Regeneration Medicine, University of California, San Francisco, San Francisco, CA, USA.
Alyssa ZhuDepartment of Neurology, University of California, San Francisco, San Francisco, CA, USA.
Matt FriessenDepartment of Obstetrics and Gynecology, University of California, San Francisco, San Francisco, CA, USA.
Roy GeronaDepartment of Obstetrics and Gynecology, University of California, San Francisco, San Francisco, CA, USA.
Hans Christian von BüdingenDepartment of Neurology, University of California, San Francisco, San Francisco, CA, USA.
Roland G HenryDepartment of Neurology, University of California, San Francisco, San Francisco, CA, USA; Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, CA, USA; Bioengineering Graduate Group, University of California, Berkeley, and San Francisco, San Francisco, CA, USA.
Stephen L HauserDepartment of Neurology, University of California, San Francisco, San Francisco, CA, USA; Program in Neuroscience, University of California, San Francisco, San Francisco, CA, USA.
Jonah R ChanDepartment of Neurology, University of California, San Francisco, San Francisco, CA, USA; Program in Neuroscience, University of California, San Francisco, San Francisco, CA, USA.
University of California, San Francisco · USUniversity of California, Berkeley · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundMultiple 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.

methodsWe 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.

findingsBetween 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.

interpretationTo 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.

fundingUniversity of California, San Francisco and the Rachleff Family.

Indexed as

AdultClemastineCross-Over StudiesDouble-Blind MethodEvoked Potentials, VisualFemaleHumansMaleMultiple SclerosisRemyelinationTomography, Optical CoherenceTreatment OutcomeClemastine

Identifiers

PMID29029896
OpenAlexW2760972505

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.