Vancomycin Study in Multiple Sclerosis (MS)

Impact of Vancomycin on the Gut Microbiome and Immune Function in Multiple Sclerosis

The overall goal of this study is to elucidate a mechanism by which vancomycin modulates the gut-brain axis in multiple sclerosis (MS). The gut microbiome plays an important role in autoimmunity, including MS. However, the identity of gut microbes modulating neuroinflammation in MS and their mechanisms of action remain obscure. Hence, here the research team proposes to investigate the effects of vancomycin on the gut microbiota composition, peripheral immune function, and brain MRI lesions in MS patients.

Study Overview

• Status: Recruiting
• Conditions: Multiple Sclerosis
• Intervention / Treatment: Drug: Vancomycin; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 12
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Susan E Filomena, BA; Phone Number: 212-2413841; Email: susan.filomena@mssm.edu
• Study Contact Backup: Name: Abigail Hintermeister, BA, MPH; Phone Number: 212-241-3391; Email: abigail.hintermeister@mssm.edu

Study Locations

• United States
  • New York
    • New York, New York, United States, 10029
      • Recruiting
      • Corinne Goldsmith Dickinson Center for Multiple Sclerosis at Mount Sinai
      • Contact: Susan E Filomena, BA; Phone Number: 212-241-3841; Email: susan.filomena@mssm.edu
      • Contact: Abigail Hintermeister, MPA; Phone Number: 212-241-3391; Email: abigail.hintermeister@mssm.edu
      • Principal Investigator: Stephanie K Tankou

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• aged 18 - 50
• newly diagnosed MS (2017 McDonald criteria), CIS or RIS patients, who have experienced symptoms no earlier than the past year
• treatment naive
• able to understand the risks, benefits, and alternatives of participation and give meaningful consent

Exclusion Criteria:

• antibiotic use within the past 90 days;
• pre- or probiotic use within past month or corticosteroids use within the past month;
• use of tobacco products within the past 1 month;
• history of treatment with immunosuppressants;
• history of gastroenteritis within the past month or diagnosis with a chronic infectious disease, i.e. hepatitis B, C or HIV;
• pregnancy or less than 6 months postpartum;
• irritable bowel syndrome and other bowel dysfunction such as constipation;
• history of bowel surgery;
• inflammatory bowel disease, rheumatoid arthritis, systemic lupus erythematosus, diabetes and any other auto-immune illness;
• diagnosis with another neurological disease, behavioral or psychiatric conditions that would be incompatible with a safe and successful participation in the study (such as severe major depression, schizophrenia and presence of psychotic symptoms);
• eating disorders such as anorexia nervosa, bulimia, or binge eating syndrome;
• travel outside of the country within the past month;
• contraindication to vancomycin including estimated glomerular filtration rate of <60ml/min, impaired hearing or known allergy.
• Contraindication to MRI such as implanted metallic objects

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Vancomycin; 125mg antibiotic taken 4 times daily by mouth	Drug: Vancomycin; A marketed antibiotic (Study Drug) supplied by Amerisource Bergen, by the Mount Sinai Investigational Drug Services (IDS), and encapsulated in red coating to match the placebo.
Placebo Comparator: Placebo; Matching placebo taken 4 times daily by mouth	Drug: Placebo; Placebo created by the IDS and encapsulated in red coating to match the Study Drug.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in abundance of butyrate producing bacteria	Changes in abundance of butyrate producing bacteria from baseline treatment up to 6 weeks	Baseline up to 6 weeks
Changes in Serum Butyrate levels	Changes in serum butyrate level from baseline treatment up to 6 weeks Butyrate is a substance that is produce when gut bacteria breaks down food. Butyrate can get into our blood circulation and regulate how our immune cells function.	Baseline up to 6 weeks
Changes in number of peripheral T cells	Change in frequency of peripheral regulatory T cells baseline treatment up to 6 weeks. T cells are a type of lymphocyte. Lymphocytes are a type of white blood cell. They make up part of the immune system. T cells help the body fight diseases or harmful substances, such as bacteria or viruses.	Baseline up to 6 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in abundance of short chain fatty acids (SCFAs)-producing bacteria	Changes in abundance of SCFA-producing bacteria	Baseline and 12 months
Change in stool SCFAs levels	Change in stool SCFAs levels SCFAs are substance that are produce when gut bacteria breaks down food.	Baseline and 12 months
Change in serum SCFAs levels	Change in serum SCFAs levels	Baseline and 12 months
Change in number of gadolium enhancing brain lesions	Change in number gadolium enhancing brain lesions A lesion is a brain injury caused by inflammation. Gadolinium is a dye that is used to visualize areas of active inflammation in the brain.	Baseline and 12 months
Change in volume of gadolium enhancing brain lesions		Baseline and 12 months
Change in number of new brain lesions		Baseline and 12 months
Change in volume of new brain lesions		Baseline and 12 months
Change in number of total brain lesions		Baseline and 12 months
Change in volume of total brain lesions		Baseline and 12 months
Changes in number of paramagnetic rim lesions	Changes in number of paramagnetic rim lesions Paramagnetic rim lesions are a type of brain injury found in MS patients.	Baseline and 12 months
Changes in volume of paramagnetic rim lesions	Changes in volume of paramagnetic rim lesions	Baseline and 12 months
Changes in thalamic brain volumes	Changes in thalamic brain volumes	Baseline and 12 months
Changes in cortical brain volumes	Changes in cortical brain volumes	Baseline and 12 months
Changes in total brain volumes	Changes in total brain volumes	Baseline and 12 months

Collaborators and Investigators

• Sponsor: Icahn School of Medicine at Mount Sinai
• Collaborators: Doris Duke Charitable Foundation
• Investigators: Principal Investigator: Stephanie K Tankou, MD, Icahn School of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): February 8, 2023
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: September 12, 2022
• First Submitted That Met QC Criteria: September 12, 2022
• First Posted (Actual): September 14, 2022

Study Record Updates

• Last Update Posted (Actual): March 22, 2024
• Last Update Submitted That Met QC Criteria: March 21, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: gut microbiome; gut-brain axis; neuroinflammation; peripheral immune function
• 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; Anti-Infective Agents; Anti-Bacterial Agents; Vancomycin
• Other Study ID Numbers: GCO-22-0462

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: The investigator is not developing the product. The study has been exempted from an IND by the FDA, since it entails the off-label use of a marketed drug.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No