Abstract：
BACKGROUND: Identification of therapies to promote repair in multiple sclerosis is challenged by the lack of an accepted trial model and associated outcome measures. The goal of this study was to determine the feasibility of a new trial model that enrolls disease modifying therapy (DMT)-treated relapsing-remitting multiple sclerosis (RRMS) participants who have enhancing lesions on clinically indicated brain MRI, and to explore estimates of lesion repair using MRI.
METHODS: This was a single site randomized controlled clinical trial. Recruitment took place between November 2015 and January 2019, with final follow-up in February 2019. DMT-treated RRMS participants aged 18-60 years with at least one gadolinium-enhancing lesion on clinically indicated brain MRI were included. Participants were randomized 2:1 to oral domperidone add-on 10-mg three times daily for 16 weeks or no add-on treatment (control). The primary outcomes were feasibility of the model pre-defined as recruitment of 24 participants within 36 months with a 79 % completion rate, and MRI outcomes of lesion repair measured at 16 and 32 weeks using texture analysis, magnetization transfer imaging (MTI), and diffusion tensor imaging (DTI). The impact of domperidone on serum prolactin at 6 and 16 weeks was also evaluated.
RESULTS: Of 237 RRMS participants screened, 17 (14 women) were randomized: 12 to domperidone add-on and 5 to control. All completed the study. Median (range) age was 38.9 (26.7-55.9) years; EDSS was 1.5 (1.0-3.5); and disease duration was 12.9 (2.9-23.3) years. Both groups showed improvement in MRI texture and diffusion fractional anisotropy (FA) at 32 weeks, and the domperidone group demonstrated additional recovery at 16 weeks in both texture and FA. There was no significant group difference in any MRI outcome. Of the 12 domperidone participants, 7 had ≥4x higher serum prolactin than normal. There were no serious adverse events.
CONCLUSIONS: The recruitment target was not met and therefore the trial model was not feasible despite a full completion rate. The imaging techniques performed well, especially MRI texture analysis, suggesting the sample size being sufficient for estimating lesion repair. The main challenge of this trial model may be recruiting gadolinium-enhancing lesions in DMT-treated RRMS participants. Prolactin is safe and may hold promise as a remyelination therapy.
BACKGROUND: ClinicalTrials.gov Identifier: NCT02493049.
METHODS: This was a single site randomized controlled clinical trial. Recruitment took place between November 2015 and January 2019, with final follow-up in February 2019. DMT-treated RRMS participants aged 18-60 years with at least one gadolinium-enhancing lesion on clinically indicated brain MRI were included. Participants were randomized 2:1 to oral domperidone add-on 10-mg three times daily for 16 weeks or no add-on treatment (control). The primary outcomes were feasibility of the model pre-defined as recruitment of 24 participants within 36 months with a 79 % completion rate, and MRI outcomes of lesion repair measured at 16 and 32 weeks using texture analysis, magnetization transfer imaging (MTI), and diffusion tensor imaging (DTI). The impact of domperidone on serum prolactin at 6 and 16 weeks was also evaluated.
RESULTS: Of 237 RRMS participants screened, 17 (14 women) were randomized: 12 to domperidone add-on and 5 to control. All completed the study. Median (range) age was 38.9 (26.7-55.9) years; EDSS was 1.5 (1.0-3.5); and disease duration was 12.9 (2.9-23.3) years. Both groups showed improvement in MRI texture and diffusion fractional anisotropy (FA) at 32 weeks, and the domperidone group demonstrated additional recovery at 16 weeks in both texture and FA. There was no significant group difference in any MRI outcome. Of the 12 domperidone participants, 7 had ≥4x higher serum prolactin than normal. There were no serious adverse events.
CONCLUSIONS: The recruitment target was not met and therefore the trial model was not feasible despite a full completion rate. The imaging techniques performed well, especially MRI texture analysis, suggesting the sample size being sufficient for estimating lesion repair. The main challenge of this trial model may be recruiting gadolinium-enhancing lesions in DMT-treated RRMS participants. Prolactin is safe and may hold promise as a remyelination therapy.
BACKGROUND: ClinicalTrials.gov Identifier: NCT02493049.
摘要：
背景：缺乏公认的试验模型和相关的结果指标，对促进多发性硬化修复的治疗方法的鉴定提出了挑战。这项研究的目的是确定一种新的试验模型的可行性，该模型可招募经过疾病修饰治疗（DMT）治疗的复发缓解型多发性硬化症（RRMS）参与者，这些参与者在临床指示的脑MRI上具有增强的病变，并使用MRI探讨病变修复的估计。
方法：这是一项单中心随机对照临床试验。招聘时间为2015年11月至2019年1月，最终随访时间为2019年2月。包括年龄在18-60岁的DMT治疗的RRMS参与者，在临床指示的脑MRI上至少有一个钆增强病变。参与者被随机分为2：1，每天3次口服多潘立酮10mg，持续16周或不进行额外治疗（对照）。主要结果是该模型的可行性，即在36个月内招募24名参与者，完成率为79%。使用纹理分析在16周和32周测量病变修复的MRI结果，磁化转移成像(MTI),和扩散张量成像（DTI）。还评估了多潘立酮在6周和16周时对血清催乳素的影响。
结果：在筛选的237名RRMS参与者中，17名（14名女性）被随机分配：12名服用多潘立酮，5名服用对照。所有人都完成了研究。中位（范围）年龄为38.9（26.7-55.9）岁；EDSS为1.5（1.0-3.5）；疾病持续时间为12.9（2.9-23.3）年。32周时，两组MRI纹理和弥散各向异性分数（FA）均有改善，多潘立酮组在16周时的质地和FA均显示出额外的恢复。任何MRI结果均无明显组间差异。在12名多潘立酮参与者中，7人血清催乳素比正常人高≥4倍。无严重不良事件发生。
结论：没有达到招募目标，因此尽管完全完成率，试验模型仍不可行。成像技术表现良好，尤其是MRI纹理分析,表明样本量足以估计病变修复。该试验模型的主要挑战可能是在DMT治疗的RRMS参与者中招募钆增强病变。催乳素是安全的，可以作为髓鞘再生疗法。
背景：ClinicalTrials.gov标识符：NCT02493049。
方法：这是一项单中心随机对照临床试验。招聘时间为2015年11月至2019年1月，最终随访时间为2019年2月。包括年龄在18-60岁的DMT治疗的RRMS参与者，在临床指示的脑MRI上至少有一个钆增强病变。参与者被随机分为2：1，每天3次口服多潘立酮10mg，持续16周或不进行额外治疗（对照）。主要结果是该模型的可行性，即在36个月内招募24名参与者，完成率为79%。使用纹理分析在16周和32周测量病变修复的MRI结果，磁化转移成像(MTI),和扩散张量成像（DTI）。还评估了多潘立酮在6周和16周时对血清催乳素的影响。
结果：在筛选的237名RRMS参与者中，17名（14名女性）被随机分配：12名服用多潘立酮，5名服用对照。所有人都完成了研究。中位（范围）年龄为38.9（26.7-55.9）岁；EDSS为1.5（1.0-3.5）；疾病持续时间为12.9（2.9-23.3）年。32周时，两组MRI纹理和弥散各向异性分数（FA）均有改善，多潘立酮组在16周时的质地和FA均显示出额外的恢复。任何MRI结果均无明显组间差异。在12名多潘立酮参与者中，7人血清催乳素比正常人高≥4倍。无严重不良事件发生。
结论：没有达到招募目标，因此尽管完全完成率，试验模型仍不可行。成像技术表现良好，尤其是MRI纹理分析,表明样本量足以估计病变修复。该试验模型的主要挑战可能是在DMT治疗的RRMS参与者中招募钆增强病变。催乳素是安全的，可以作为髓鞘再生疗法。
背景：ClinicalTrials.gov标识符：NCT02493049。
