Multiomics Targeting Microbiome Associated Changes in Stroke Patients (StrokeMicroBiomics) (SMB)

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.

Study Overview

• Status: Completed
• Conditions: Ischemic Stroke; Transient Ischemic Attack
• Intervention / Treatment: Diagnostic test: Microbiome and Plasma Characterisation

Detailed Description

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.

• Study Type: Observational
• Enrollment (Actual): 10

Contacts and Locations

Study Locations

• Germany
  • Bavaria
    • Munich, Bavaria, Germany, 81377
      • LMU University hospital, Munich

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Participants are recruited and samples taken within 7 days of either stroke or TIA onset.

Description

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)

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Severe Ischemic Stroke; Severe Stroke as defined by inclusion criteria	Diagnostic test: Microbiome and Plasma Characterisation; Flow Cytometry, Mass-Spectometry, Shotgun-Sequencing
Mild Ischemic Stroke; Mild Stroke as defined by inclusion criteria	Diagnostic test: Microbiome and Plasma Characterisation; Flow Cytometry, Mass-Spectometry, Shotgun-Sequencing
Transient Ischemic Attack; Transient Ischemic Attack as defined by inclusion criteria	Diagnostic test: Microbiome and Plasma Characterisation; Flow Cytometry, Mass-Spectometry, Shotgun-Sequencing

What is the study measuring?

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	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

Collaborators and Investigators

• Sponsor: Ludwig-Maximilians - University of Munich
• Collaborators: University of Luxembourg

Study record dates

Study Major Dates

• Study Start (Actual): June 16, 2019
• Primary Completion (Actual): December 1, 2022
• Study Completion (Actual): June 1, 2023

Study Registration Dates

• First Submitted: March 12, 2020
• First Submitted That Met QC Criteria: March 18, 2020
• First Posted (Actual): March 20, 2020

Study Record Updates

• Last Update Posted (Actual): October 15, 2024
• Last Update Submitted That Met QC Criteria: October 9, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: Microbiome; Immune System; Metabolome; Brain Lesion; Gut-Brain Axis
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Brain Ischemia; Stroke; Ischemic Stroke; Ischemia; Ischemic Attack, Transient
• Other Study ID Numbers: Synergy ID 390857198 SMB

Drug and device information, study documents

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