Microbiome Benchmarking to Identify Perturbations in Multiple Sclerosis II

The goal of this longitudinal study is to (1) explore the association between the gut microbiota and inflammatory disease activity in early onset multiple sclerosis, (2) investigate whether/how gut microbial composition vary when patients experience a relapse, and (3) to assess whether the gut microbiota shows increased similarities between affected pairs of first-degree relatives within the same family when compared with discordant pairs of first-degree relatives.

Study Overview

• Status: Completed
• Conditions: Multiple Sclerosis
• Intervention / Treatment: Other: Magnetic resonance imaging (MRI)

Detailed Description

Using metagenomics, as well as clinical, immunological, and radiological observations, the investigators will investigate if active relapsing-remitting multiple sclerosis patients have a more pro-inflammatory gut microbiota signature than multiple sclerosis patients with less active disease and matched healthy controls.

More specifically, the investigators will investigate whether temporal variability of the gut microbiota is related to inflammatory disease activity in multiple sclerosis, whether changes in the gut microbiota are predictive of future inflammatory disease activity in multiple sclerosis, and whether gut microbiota characteristics are predictive of the disease course after 2 years.

• Study Type: Interventional
• Enrollment (Actual): 250
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Belgium
  • Brussel
    • Jette, Brussel, Belgium, 1090
      • Universitair Ziekenhuis Brussel
  • Vlaams-Brabant
    • Melsbroek, Vlaams-Brabant, Belgium, 1820
      • Nationaal Multiple Sclerose Centrum Melsbroek

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria patients:

• Diagnosis of MS (as defined by the 2010 McDonald criteria).
• Occurrence of symptoms no longer than 5 years before baseline.
• Aged 18-65.
• Willingness to participate in the study and to sign the informed consent.

Exclusion Criteria patients:

• Treatment with high doses of systemic steroids 2 months before baseline.
• Use of antibiotics 3 months before baseline.
• Chronic gastrointestinal disease (e.g. inflammatory bowel disease, colon cancer).
• Other immune-mediated or autoimmune diseases (e.g. rheumatoid arthritis, diabetes type 1 and 2, psoriasis).

Additional inclusion criteria for MS patients undergoing a relapse:

• Ability to provide a faecal sample within 4 weeks from onset of the first symptoms suggestive of a relapse, before cortisone treatment. A relapse is defined by a new clinical sign or clinical worsening of a previous sign/symptom persisting for >=24 hours in the absence of fever.

Additional exclusion criteria for MS patients undergoing a relapse:

• Treatment with cortisone before collection of baseline faecal sample.
• Evidence of a relapse less than 2 months before baseline.
• Switching disease modifying treatment less than 2 months before baseline.

Inclusion criteria healthy controls:

• Willingness to participate to the study and to sign the informed consent.
• Aged >=18.

Exclusion criteria healthy controls:

• Neurodegenerative disorders.
• Chronic gastrointestinal disease (e.g. inflammatory bowel disease, colon cancer) or autoimmune diseases (e.g. rheumatoid arthritis, diabetes type 1, psoriasis).
• Use of antibiotics 3 months before baseline.
• Treatment with high doses of systemic steroids 2 months before baseline.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Multiple sclerosis (MS) patients; Patients will undergo magnetic resonance imaging (MRI). Stool and blood samples will be collected.	Other: Magnetic resonance imaging (MRI); MRI scanner
No Intervention: Healthy controls; Healthy controls will not undergo magnetic resonance imaging (MRI). Stool and blood samples will be collected.
No Intervention: Multiple sclerosis (MS) patients undergoing a relapse; Multiple sclerosis (MS) patients undergoing a relapse will not undergo magnetic resonance imaging (MRI). Stool and blood samples will be collected.
No Intervention: Multiple sclerosis (MS) patients from multiplex MS families; Multiple sclerosis (MS) patients from multiplex MS families will not undergo magnetic resonance imaging (MRI). Stool and blood samples will be collected.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical evidence for active disease	Time to first relapse (after baseline) will be reported for all patients.	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Radiological evidence for active disease	Occurrence of new contrast-enhancing T1 hyper intense lesions, or changes in white matter lesion volume (i.e. new or enlarging T2 hyper intense lesions)	3 years

Collaborators and Investigators

• Sponsor: National MS Center Melsbroek
• Investigators: Principal Investigator: Marie D'hooghe, M.D., National MS Center Melsbroek

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2018
• Primary Completion (Actual): November 1, 2021
• Study Completion (Actual): May 1, 2022

Study Registration Dates

• First Submitted: March 5, 2018
• First Submitted That Met QC Criteria: January 8, 2019
• First Posted (Actual): January 9, 2019

Study Record Updates

• Last Update Posted (Actual): May 11, 2022
• Last Update Submitted That Met QC Criteria: May 10, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Multiple Sclerosis; Sclerosis
• Other Study ID Numbers: 2018BDM2

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No