多发性硬化
医学
安慰剂
临床终点
富马酸二甲酯
不利影响
内科学
交叉研究
随机对照试验
胃肠病学
免疫学
病理
替代医学
作者
Ari Green,Jeffrey M. Gelfand,Bruce Cree,Carolyn Bevan,W. John Boscardin,Feng Mei,Justin Inman,Sam Arnow,Michael Devereux,Aya Abounasr,Hiroko Nobuta,Alyssa H. Zhu,Matt Friessen,Roy Gerona,Hans‐Christian von Büdingen,Roland G. Henry,Stephen L. Hauser,Jonah R. Chan
出处
期刊:The Lancet
[Elsevier]
日期:2017-12-01
卷期号:390 (10111): 2481-2489
被引量:432
标识
DOI:10.1016/s0140-6736(17)32346-2
摘要
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.
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