■尽管在多发性硬化症(MS)的免疫调节治疗方面取得了进展,非活动性进行性多发性硬化(PMS)患者继续面临重大未满足的需求.脱髓鞘,阴燃的炎症和神经变性是残疾进展的重要驱动因素,目前的治疗方法没有足够的针对性。有希望的临床前数据支持二甲双胍用于治疗PMS的用途。这项临床试验的目的是评估二甲双胍,作为附加治疗,在延迟非活动性PMS患者的疾病进展方面优于安慰剂。
■MACSiMiSE-BRAIN是一种多中心双臂,1:1随机化,三盲,安慰剂对照临床试验,在比利时的五个地点进行。计划招募120例非活动性PMS患者。每位参与者将接受一次筛查访问,评估基线磁共振成像(MRI),临床试验,问卷,和安全实验室评估。随机化后,参与者将被分配到治疗组(二甲双胍)或安慰剂组.随后,他们将接受96周的随访。主要结果是步行速度的变化,通过定时25英尺步行测试测量,从基线到96周。次要结局指标包括神经系统残疾的变化(扩展残疾状态评分),信息处理速度(符号数字模式测试)和手功能(9孔钉测试)。将进行年度脑MRI以评估脑容积和扩散指标的演变。由于患者可能不会在所有领域进步,复合结果,将额外评估总体残疾反应评分作为探索性结果.其他探索性结果将包括顺磁性边缘病变,2分钟步行测试和健康经济分析,以及患者和护理人员报告的结果,如EQ-5D-5L,多发性硬化影响量表和照顾者应变指数。
■在提交给中央欧洲临床试验信息系统后,获得了监管机构[伦理委员会和联邦药品和健康产品局(FAMHP)]的临床试验授权。这项临床试验的结果将在科学会议上传播,在同行评审的出版物中,患者协会和公众。
■ClinicalTrials.gov标识符:NCT05893225,EUCT编号:2023-503190-38-00。
UNASSIGNED: Despite advances in immunomodulatory treatments of multiple sclerosis (MS), patients with non-active progressive multiple sclerosis (PMS) continue to face a significant unmet need. Demyelination, smoldering inflammation and neurodegeneration are important drivers of disability progression that are insufficiently targeted by current treatment approaches. Promising preclinical data support repurposing of metformin for treatment of PMS. The objective of this clinical
trial is to evaluate whether metformin, as add-on treatment, is superior to placebo in delaying disease progression in patients with non-active PMS.
UNASSIGNED: MACSiMiSE-BRAIN is a multi-center two-arm, 1:1 randomized, triple-blind, placebo-controlled clinical
trial, conducted at five sites in Belgium. Enrollment of 120 patients with non-active PMS is planned. Each participant will undergo a screening visit with assessment of baseline magnetic resonance imaging (MRI), clinical tests, questionnaires, and a safety laboratory assessment. Following randomization, participants will be assigned to either the treatment (metformin) or placebo group. Subsequently, they will undergo a 96-week follow-up period. The primary outcome is change in walking speed, as measured by the Timed 25-Foot Walk Test, from baseline to 96 weeks. Secondary outcome measures include change in neurological disability (Expanded Disability Status Score), information processing speed (Symbol Digit Modalities Test) and hand function (9-Hole Peg test). Annual brain MRI will be performed to assess evolution in brain volumetry and diffusion metrics. As patients may not progress in all domains, a composite outcome, the Overall Disability Response Score will be additionally evaluated as an exploratory outcome. Other exploratory outcomes will consist of paramagnetic rim lesions, the 2-minute walking test and health economic analyses as well as both patient- and caregiver-reported outcomes like the EQ-5D-5L, the Multiple Sclerosis Impact Scale and the Caregiver Strain Index.
UNASSIGNED: Clinical
trial authorization from regulatory agencies [Ethical Committee and Federal Agency for Medicines and Health Products (FAMHP)] was obtained after submission to the centralized European Clinical
Trial Information System. The results of this clinical
trial will be disseminated at scientific conferences, in peer-reviewed publications, to patient associations and the general public.
UNASSIGNED: ClinicalTrials.gov Identifier: NCT05893225, EUCT number: 2023-503190-38-00.