Multiomics Targeting Microbiome Associated Changes in Stroke Patients (StrokeMicroBiomics)

Study Overview
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Brief Summary
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Preclinical research has established a convincing connection between changes in the gut microbiota composition and stroke outcome. However clinical data on the gut-brain axis, and its chronic characteristics, is sparse. Additional investigations in the context of ischemic stroke regarding the relationship between dysbiosis and functional changes of the microbiome, as characterized by the metabolome, are still required. The StrokeMicroBiomics study will offer insight into these mechanisms and offer new potential targets for therapeutic interventions. The primary objective is the characterisation of gut dysbiosis in ischemic stroke patients in the acute phase after stroke and during a 3 month follow-up period. The secondary objectives include the identification of dysregulated gut microbiome metabolites and key immune cell populations in addition to the clinical progression of the study participants during the 3 month follow-up period after disease onset.

Detailed Description
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Results of experimental, preclinical studies suggest that microbiome-targeted may improve stroke outcome as well as stroke-related comorbidities. Yet, clinical trials describing the extent and time course of microbiome changes after stroke are currently not available. Moreover, the impact of post-stroke dysbiosis on metabolic changes and the systemic immunity are unexplored. Therefore, the primary objective of this trial is the characterization of gut dysbiosis progression in ischemic stroke patients during a 3 month follow-up period . The secondary objectives include the identification of dysregulated gut microbiome metabolites and key immune cell populations in addition to the clinical progression of the study participants during the 3 month follow-up period after disease onset. In order to elucidate the differential impact of lesion size on immune and microbiome homeostasis, separate patient cohorts with mild and severe stroke will be studied. Furthermore, to control for the effects of temporary focal neurological deficits and stress induced microbiome and immune changes, patients with stroke mimics and transient ischemic attacks (TIA) are being recruited to the control group.

Official Title
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Multiomics Targeting Microbiome Associated Changes in Stroke Patients (StrokeMicroBiomics)

Conditions
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Ischemic Stroke, Transient Ischemic Attack

Intervention / Treatment
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* Diagnostic Test: Microbiome and Plasma Characterisation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written consent as submitted and approved to the human subjects review board must be gathered from the participants Participants must be at least 50 years of age For the severe stroke cohort, eligibility is defined by: CT or MRI confirmed ischemic stroke affecting at least 1/3 of the anterior, medial or posterior cerebral arteries cortical coverage NIHSS of at least 10 at time of induction into emergency room Ischemic Stroke occured within the last 7 days For the mild stroke cohort, eligibility is defined by: CT or MRI confirmed ischemic stroke affecting no more than 1/3 of the anterior, medial or posterior cerebral arteries cortical coverage NIHSS between 1 and 10 at time of induction into emergency room Ischemic Stroke occured within the last 7 days For the TIA cohort, eligibility is defined by: CT or MRI confirmed absence of a lesion NIHSS of 0 no more than 24 hours after induction into emergency room TIA occured within the last 7 days Exclusion Criteria: Pregnancy Diagnosed and malignant Tumor ailment Active, non-stroke related immunosuppression (i.e. HIV) Infection, operative procedure or antibiotics treatment within 4 weeks prior to stroke/TIA Relevant autoimmune disease (i.e Morbus Crohn) Chronic infectious diseases (i.e Hepatitis C) Hemorrhagic Stroke or intracranial bleeding Cerebellar lesions Other neurodegenerative diseases (i.e. Parkinson´s Disease or Alzheimers Dementia)

Ages Eligible for Study
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Minimum 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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Severe Ischemic Stroke<br>Severe Stroke as defined by inclusion criteria | Diagnostic Test: Microbiome and Plasma Characterisation<br>* Flow Cytometry, Mass-Spectometry, Shotgun-Sequencing<br>|
| Mild Ischemic Stroke<br>Mild Stroke as defined by inclusion criteria | Diagnostic Test: Microbiome and Plasma Characterisation<br>* Flow Cytometry, Mass-Spectometry, Shotgun-Sequencing<br>|
| Transient Ischemic Attack<br>Transient Ischemic Attack as defined by inclusion criteria | Diagnostic Test: Microbiome and Plasma Characterisation<br>* Flow Cytometry, Mass-Spectometry, Shotgun-Sequencing<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes from Baseline in the Gut Microbiome Composition at 3 Months post Stroke/TIA | Gut Microbiome Composition is assessed using Shotgun Sequencing | 1-7 Days and 90 Days after Stroke | 
| Changes from Baseline of the Gut Metabolome as measured in Blood and Stool at 3 Months post Stroke/TIA | The Metabolome is measured using Mass-Spectometry | 1-7 Days and 90 Days after Stroke | 
| Changes from Baseline in key Immune Populations at 3 Months post Stroke/TIA | Immune Populations are measured using Flow Cytometry | 1-7 Days and 90 Days after Stroke | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| National Institute of Health Stroke Scale (NIHSS) |  | 1-7 days and 90 days after stroke | 
| Modified Rankin Score (mRS) |  | 1-7 days and 90 days after stroke | 
| CT and (if available) MRI documentation |  | 1-7 days and 90 days after stroke | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Microbiome, Immune System, Metabolome, Brain Lesion, Gut-Brain Axis