Vancomycin Study in Multiple Sclerosis (MS)

Study Overview
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Brief Summary
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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.

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

Conditions
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Multiple Sclerosis

Intervention / Treatment
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* Drug: Vancomycin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Placebo-controlled blinded trial
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vancomycin<br>125mg antibiotic taken 4 times daily by mouth | Drug: Vancomycin<br>* 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.<br>|
| Placebo Comparator: Placebo<br>Matching placebo taken 4 times daily by mouth | Drug: Placebo<br>* Placebo created by the IDS and encapsulated in red coating to match the Study Drug.<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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gut microbiome, peripheral immune function, neuroinflammation, gut-brain axis