PDF(Pubmed)
Abstract：
BACKGROUND: Remyelination failure hampers symptomatic recovery in multiple sclerosis (MS), underlining the importance of developing remyelinating therapies. Optic neuritis is currently the most established method of measuring remyelination in MS trials. Complementary more generalisable methods of measuring remyelination are required to confirm treatment efficacy. Measuring internuclear ophthalmoplegia (INO) with infrared oculography provides such a method. Moreover, this method can be expanded with a test for selecting likely treatment responders by using fampridine. The aim of this trial is to investigate the (long-term) remyelinating effects of clemastine fumarate in patients with MS and INO and to evaluate if treatment response can be predicted using fampridine.
METHODS: RESTORE is a single-centre double-blind randomised placebo-controlled trial of clemastine fumarate versus placebo. Prior to clemastine treatment improvement in oculographic features of INO after a single 10 mg dose of fampridine is measured in all participants and used to predict the treatment response to clemastine. Eighty individuals with MS and INO will be 1:1 randomised to 4 mg of clemastine fumarate two times a day for 6 months or equivalent placebo. Our primary outcome is improvement in the Versional Dysconjugacy Index-area under the curve, measured by infrared oculography after 6 months of treatment. Participants are assessed for persistent treatment effects 6, 18 and 30 months after end of treatment. Secondary outcome measures include other oculography parameters including double-step saccades, retinal imaging, visual acuities, physical disability, cognition and patient-reported outcomes.
BACKGROUND: Clemastine is a registered and very well-established drug with well-known safety and side effects. The protocol was approved by the medical ethical committee of the Amsterdam UMC, location VUMC and the Dutch Central Committee on Research Involving Human Subject. Written informed consent is obtained from all participants. The results will be published in peer-reviewed medical scientific journals.
BACKGROUND: EudraCT: 2021-003677-66, ClinicalTrials.gov: NCT05338450.
METHODS: RESTORE is a single-centre double-blind randomised placebo-controlled trial of clemastine fumarate versus placebo. Prior to clemastine treatment improvement in oculographic features of INO after a single 10 mg dose of fampridine is measured in all participants and used to predict the treatment response to clemastine. Eighty individuals with MS and INO will be 1:1 randomised to 4 mg of clemastine fumarate two times a day for 6 months or equivalent placebo. Our primary outcome is improvement in the Versional Dysconjugacy Index-area under the curve, measured by infrared oculography after 6 months of treatment. Participants are assessed for persistent treatment effects 6, 18 and 30 months after end of treatment. Secondary outcome measures include other oculography parameters including double-step saccades, retinal imaging, visual acuities, physical disability, cognition and patient-reported outcomes.
BACKGROUND: Clemastine is a registered and very well-established drug with well-known safety and side effects. The protocol was approved by the medical ethical committee of the Amsterdam UMC, location VUMC and the Dutch Central Committee on Research Involving Human Subject. Written informed consent is obtained from all participants. The results will be published in peer-reviewed medical scientific journals.
BACKGROUND: EudraCT: 2021-003677-66, ClinicalTrials.gov: NCT05338450.
摘要：
背景：多发性硬化症（MS）的髓鞘再生失败阻碍症状恢复，强调开发髓鞘再生疗法的重要性。视神经炎是目前MS试验中最成熟的测量髓鞘再生的方法。需要补充更普遍的测量髓鞘再生的方法来确认治疗效果。用红外眼图测量核间眼肌麻痹(INO)提供了这样一种方法。此外，该方法可以通过使用fampridine选择可能的治疗应答者的测试来扩展。该试验的目的是研究富马酸氯马斯汀对MS和INO患者的（长期）髓鞘再生作用，并评估是否可以使用氨吡啶预测治疗反应。
方法：RESTORE是一项富马酸氯马斯汀与安慰剂的单中心双盲随机安慰剂对照试验。在氯马斯汀治疗之前，在所有参与者中测量单次10mg剂量的famprindine后，INO的眼图特征得到改善，并用于预测对氯马斯汀的治疗反应。患有MS和INO的80名个体将以1：1随机分配至4mg富马酸氯马斯汀，每天两次，持续6个月或等效安慰剂。我们的主要结果是改善了垂直接合不良指数-曲线下面积，治疗6个月后通过红外眼图测量。在治疗结束后6、18和30个月评估参与者的持续治疗效果。次要结果指标包括其他眼图参数，包括双步扫视，视网膜成像,视力,身体残疾,认知和患者报告的结果。
背景：氯马斯汀是一种注册且非常完善的药物，具有众所周知的安全性和副作用。该协议得到了阿姆斯特丹UMC医学伦理委员会的批准，位置VUMC和荷兰涉及人类受试者的研究中央委员会。从所有参与者获得书面知情同意书。研究结果将发表在同行评审的医学期刊上。
背景：EudraCT：2021-003677-66，ClinicalTrials.gov：NCT05338450。
方法：RESTORE是一项富马酸氯马斯汀与安慰剂的单中心双盲随机安慰剂对照试验。在氯马斯汀治疗之前，在所有参与者中测量单次10mg剂量的famprindine后，INO的眼图特征得到改善，并用于预测对氯马斯汀的治疗反应。患有MS和INO的80名个体将以1：1随机分配至4mg富马酸氯马斯汀，每天两次，持续6个月或等效安慰剂。我们的主要结果是改善了垂直接合不良指数-曲线下面积，治疗6个月后通过红外眼图测量。在治疗结束后6、18和30个月评估参与者的持续治疗效果。次要结果指标包括其他眼图参数，包括双步扫视，视网膜成像,视力,身体残疾,认知和患者报告的结果。
背景：氯马斯汀是一种注册且非常完善的药物，具有众所周知的安全性和副作用。该协议得到了阿姆斯特丹UMC医学伦理委员会的批准，位置VUMC和荷兰涉及人类受试者的研究中央委员会。从所有参与者获得书面知情同意书。研究结果将发表在同行评审的医学期刊上。
背景：EudraCT：2021-003677-66，ClinicalTrials.gov：NCT05338450。
