RecruitingNot ApplicableNCT05779449

Targeting the Gut Dysbiosis to Treat Inflammation-driven Synaptopathy in MS

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

Sponsor

Neuromed IRCCS

Enrollment

100 participants

Start Date

Jul 26, 2023

Study Type

INTERVENTIONAL

Conditions

Patient Participation

Summary

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.

Eligibility

Min Age: 18 YearsMax Age: 65 Years

Inclusion Criteria7

RRMS diagnosis, as Polman et al 2011. 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.

Exclusion Criteria8

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.

Interventions

DIETARY_SUPPLEMENTPrebiotics and Probiotics supplementation

From the 1st day to the 15th day (included) patients with MS in the Pre-Pro group will receive daily: 1 capsule of Probactiol Duo, Metagenics (6 billions of Saccharomyces boulardii and 8,5 billions of probiotics including Bifidobacterium lactis Bi-07®, Bifidobacterium lactis Bl-04, Lacticaseibacillus paracasei Lpc-37, Lactobacillus acidophilus NCFM®) 1. packet of Probactiol Stips, Metagenics (4 g inulin enriched with oligofructose) From the16th day to the 365th day (included) patients with MS in the Pre-Pro group will receive daily: 2. capsules of Probactiol HMO Combi, Metagenics (7,5 billions of Lactobacillus acidophilus NCFM®, 7,5 billions of Bifidobacterium lactis Bi-07®, 2,5 ug Vitamine D3, 320 ug Vitamine A, 100 mg Threonine, 250 mg 2'-Fucosyllactose).

DIETARY_SUPPLEMENTPlacebo supplementation

1-year supplementation with two placebo capsules/day containing starch, the probiotic bacteria carrier.

PROCEDUREperipheral blood withdrawal

40 ml of blood for the isolation of Peripheral Blood Cells (PBMCs) and T cells.

PROCEDURETranscranial Magnetic Stimulation (TMS)

Intermittent theta burst stimulation (iTBS) protocol