Targeting the Gut Dysbiosis to Treat Inflammation-driven Synaptopathy in Multiple Sclerosis

Neuromed IRCCS2 个研究点分布在 1 个国家目标入组 100 人开始时间: 2023年7月26日最近更新: 2023年8月14日

适应症

试验速览

阶段: 不适用
状态: 招募中
发起方
入组人数: 100
试验地点: 2
主要终点: Changes in gut microbiota diversity or composition

研究概览研究设计入排标准结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

Inflammatory synaptopathy is a prominent pathogenic process in multiple sclerosis (MS) induced by imbalanced immune system homeostasis. Its persistence causes excitotoxic neuronal damage, leading to motor and cognitive deficits. Although many advances have been made in MS treatment, the development of effective strategies for managing disease progression driven by excitotoxic synaptic dysfunctions is of great significance. Gut dysbiosis is commonly associated with both MS and obesity and high-fat diet (HFD) can exacerbate disease by acting on gut microbiota.

Since gut microbiota can shape the immune response and brain functions, we propose to target gut dysbiosis by dietary supplementation of prebiotics and probiotics (Pre-Pro) to treat synaptopathy in both human and experimental model of MS, even when exacerbated by HFD. Overall, this project aims at unveiling the anti-inflammatory and neuroprotective pathways activated by Pre-Pro supplementation to modulate the immune-synaptic axis.

详细描述

MS is a chronic autoimmune neurodegenerative disease characterized by different forms. The most common is the relapsing-remitting (RR)MS showing a significant dysregulation of immune homeostasis.

Disease progression occurring during MS, is not only driven by infiltrating T cells destroying myelin during relapses, indeed proinflammatory molecules can also trigger a glutamate-induced excitotoxic synaptopathy promoting neurodegenerative processes and negatively influencing disease course.

Inflammation, synaptopathy and neurodegeneration are intermingled with reparative processes in different proportions, making the MS course unpredictable and the treatment approach challenging. Lifestyle habits can contribute to the heterogeneity of MS pathophysiology. In this context, the gut microbiota is emerging as a key sensor of lifestyle indeed it is continuously modulated by many factors, particularly dietary habits, and by controlling the immune system homeostasis can influence the onset and progression of MS.

HFD exacerbates MS by promoting neuroinflammation and affects gut microbiota inducing dysbiosis.

Gut dysbiosis in MS is associated with increased microglia activation and imbalance between pathogenic Th1/Th17 and tolerogenic regulatory T (Treg cells), however its effects on immune-mediated synaptopathy and their underlying mechanisms in MS have not yet been investigated.

研究设计

研究类型: Interventional
分配方式: Randomized
干预模型: Parallel
主要目的: Treatment
盲法: Double (Participant, Care Provider)

入排标准

年龄范围: 18 Years 至 65 Years（Adult, Older Adult）
性别: All
接受健康志愿者: 否

入选标准

•RRMS diagnosis, as Polman et al
•Ann Neurol. PMID: 21387374
•Age <= 18 and => 65 years
•EDSS score <= 7
•Disease duration < 10 years
•On DMF or Ocrelizumab treatment from at least 3 months
•No corticosteroid administration in the previous month
•Ability to provide written informed consent.

排除标准

•Adverse effects to gadolinium
•Blood count basal alteration
•Pregnant or lactating women
•Vegetarians or vegans
•Taking antibiotics, any product or supplement containing probiotics, Omega 3 or other antioxidant supplements within 30 days prior to inclusion
•History of food allergies or food intolerance
•Clinically significant medical condition other than MS, (latent infections, other autoimmune disease)
•Diagnosis of past eating disorders (anorexia, bulimia, or binge eating) or relevant psychiatric disorders.