The Gut Microbiome in Adult Multiple Sclerosis (MICROMS5Y)

Microbiome Benchmarking to Identify Perturbations in Multiple Sclerosis I

This study aims to assess the following research questions:

1. Map and benchmark the gut microbiome of patients with RRMS, and PPMS versus matched healthy controls
2. Determine whether RRMS or PPMS have a unique bias for a gut microbiome classification recently characterized.
3. Search for relationship with inflammation, amino acid plasma levels, heart rate variability (vagus nerve tone) and hair cortisol as a biological marker of chronic stress
4. Determine whether the gut microbiome is different in MS patients during a relapse.
5. Determine whether the gut microbiome remains stable after 3 months

Study Overview

• Status: Completed
• Conditions: Multiple Sclerosis

Detailed Description

This study is a prospective multi-center cohort study (University Hospital Brussels, National Multiple Sclerosis Center Melsbroek). This is an exploratory study and there is no specific outcome on which a power calculation can be made. We will include different subgroups of patients with MS: stable non-benign RRMS, PPMS, benign MS [Benign MS is defined as RRMS with an EDSS ≤ 3, 15 years after disease onset], RRMS during a relapse (before the administration of corticosteroids) [Relapses are defined as the development of new or recurrent neurologic symptoms not associated with fever or infection or change in medication, lasting at least 24 hours, and accompanied by new, objective neurologic findings]. Age and sex matched healthy controls will be included as well. All participants will provide a faecal, hair, and blood sample twice (baseline and after 3 months). Patients will be assessed clinically at baseline, 3 months after baseline, and approximately 1, 2, 4.5 years after baseline.

The results of this study have the potential to identify novel simple strategies to strengthen or alter the microbiome ecosystem and strengthen the overall treatment process. In case of a positive result, this would form the basis for a follow-up study on medical modulation of the microbiome with the aim of finding new treatment options for MS.

• Study Type: Observational
• Enrollment (Actual): 152

Contacts and Locations

Study Locations

• Belgium
  • Brussel-Hoofdstedelijk-Gewest
    • Jette, Brussel-Hoofdstedelijk-Gewest, 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 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

This is an exploratory study and there is no specific outcome on which a power calculation can be made. We included 122 patients with MS and 30 age and sex matched healthy controls as well.

Description

Inclusion Criteria:

1. Signed written informed consent.
2. RRMS or PPMS, as defined by the McDonald criteria.
3. Ages 18-65 years.
4. EDSS < 7
5. Treatment with IFN-beta

Exclusion Criteria:

1. SPMS without relapses during the past year at screening.
2. Use of high dose systemic steroids within the last 2 months.
3. Gastrointestinal disease, such as inflammatory bowel disease
4. Use of antibiotics within the last 4 weeks.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
MICROMS; No intervention will be administered. Stool, hair, and blood samples will be collected at baseline and three months post baseline. Clinical follow-up will occur at year 1, 2, and 4.5 (neurological consultation) and in-between visits (regular follow-up).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sustained disability worsening	Sustained disability worsening will be assessed using the Expanded Disability Status Scale (EDSS)-Plus outcome. This is a composite measure that assesses disability worsening based on changes of the EDSS score (difference of at least 1.5;1.0;0.5 depending on baseline score), the timed 25-foot walk (T25FW) score (>=20%), and the 9-hole peg test (9-HPT) score (>=20%). If worsening of any of these measures occurred, the patient has clinically deteriorated according to the EDSS-Plus outcome.	5 years

Secondary 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. Annualized relapse frequency	5 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): October 2, 2013
• Primary Completion (Actual): September 16, 2019
• Study Completion (Actual): April 1, 2020

Study Registration Dates

• First Submitted: June 10, 2021
• First Submitted That Met QC Criteria: June 10, 2021
• First Posted (Actual): June 18, 2021

Study Record Updates

• Last Update Posted (Actual): July 23, 2021
• Last Update Submitted That Met QC Criteria: July 16, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Keywords: gut microbiome
• 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: MICROMS5Y

Drug and device information, study documents

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