Gut Microbiota and Serum Markers for Cognitive Impairment and Poor Prognosis After Ischemic Stroke

Predictive Value of Gut Microbiota and Serum Markers for Cognitive Impairment and Poor Prognosis After Ischemic Stroke: A Multiple Center Cohort Study

Post-stroke cognitive impairment(PSCI) is one of the most important factors causing disabilities after stroke. Recent study found that gut microbiota plays a key role in neurological diseases. Two recent small sample studies reported gut dysbiosis in PSCI patients. In order to further verify the relationship between PSCI and gut microbiota and the predictive value of gut microbiota and serum markers for cognitive impairment and poor prognosis after ischemic stroke. The study intended to collect stool specimens of patients with acute ischemic stroke and assess their cognitive psychological state, and to establish a prospective multi-center follow-up cohort to explore the correlation between the dynamic changes of intestinal flora in patients with stroke and PSCI and poor prognosis of stroke.

Study Overview

• Status: Recruiting
• Conditions: Ischemic Stroke

• Study Type: Observational
• Enrollment (Anticipated): 600

Contacts and Locations

• Study Contact: Name: Yin Jia, Master; Phone Number: +86 13802964883; Email: jiajiayin@139.com
• Study Contact Backup: Name: Zhang Mingsi, Master; Phone Number: +86 13827003570; Email: meens19@qq.com

Study Locations

• China
  • Guangdong
    • Guanzhou, Guangdong, China, 510515
      • Recruiting
      • Department of Neurology, Nanfang Hospital, Southern Medical University
      • Contact: Yin Jia, master's degree; Phone Number: +8613802964883; Email: jiajiayin@139.com
      • Contact: Zhang Mingsi; Phone Number: +8613827003570; Email: meens@qq.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients with ischemic stroke within 7 days of onset

Description

Inclusion Criteria:

• Meet the diagnostic criteria for acute ischemic stroke;
• Aged between 18-75;
• Onset within 7 days;
• Sign informed consent and agree to provide relevant medical history data and biological specimens.

Exclusion Criteria:

• Patients diagnosed with TIA
• Severe disturbance of consciousness (NIHSS consciousness score > 1)
• Previous severe mental disorders and dementia (AD8 score ≥ 2)
• History of cerebral hemorrhage or any stroke within 12 months;
• Serious systemic diseases including malignant tumors
• Patients with aphasia and unable to cooperate to complete the Montreal Cognitive Assessment (MoCA)
• ALT or AST greater than 2 times the upper limit of normal value or severe liver disease;
• GFR less than 30mL/min/1.72m2 or severe kidney disease
• Alcohol abused, drug use and chemical poisoning history (such as pesticide poisoning)
• Patients with previous history of gastrointestinal tract or confirmed during hospitalization
• Patients who could not collect stool samples within 4 days after admission.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
ischemic stroke; Patients with ischemic stroke within 7 days of onset

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mini-Mental State Examination	A cognitive function screening test ranged 0-30, higher scores mean better cognitive function	7 days after admission
Mini-Mental State Examination	A cognitive function screening test ranged 0-30, higher scores mean better cognitive function	3 months after discharge
Mini-Mental State Examination	A cognitive function screening test ranged 0-30, higher scores mean better cognitive function	6 months after discharge
Montreal Cognitive Assessment	A cognitive function screening test ranged 0-30, higher scores mean better cognitive function	7 days after admission
Montreal Cognitive Assessment	A cognitive function screening test ranged 0-30, higher scores mean better cognitive function	3 months after discharge
Montreal Cognitive Assessment	A cognitive function screening test ranged 0-30, higher scores mean better cognitive function	6 months after discharge
Gut microbiota	Results of fecal bacteria by 16s RNA sequencing	2 days after admission
Gut microbiota	Results of fecal bacteria by 16s RNA sequencing	3 months after discharge

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Modified Rankin Scale(mRS)	A neurological function score scale ranged 0-6, higher scores mean worse neurological outcome	7 days after admission
Modified Rankin Scale(mRS)	A neurological function score scale ranged 0-6, higher scores mean worse neurological outcome	3 months after discharge
Modified Rankin Scale(mRS)	A neurological function score scale ranged 0-6, higher scores mean worse neurological outcome	6 months after discharge
Modified Rankin Scale(mRS)	A neurological function score scale ranged 0-6, higher scores mean worse neurological outcome	12 months after discharge
National Institute of Health stroke scale(NIHSS)	Neurological function score scale, ranged 0-42, higher scores mean more severe neurological deficit	Day 1 of admission
National Institute of Health stroke scale(NIHSS)	Neurological function score scale, ranged 0-42, higher scores mean more severe neurological deficit	Day 7 of admission
National Institute of Health stroke scale(NIHSS)	Neurological function score scale, ranged 0-42, higher scores mean more severe neurological deficit	3 months after discharge
National Institute of Health stroke scale(NIHSS)	Neurological function score scale, ranged 0-42, higher scores mean more severe neurological deficit	6 months after discharge
Short chain fatty acids	A metabolites of gut microbiota from stool, detected by gas chromatography-mass spectrometry (GC-MS) combined technique	2 days after admission
Short chain fatty acids	A metabolites of gut microbiota from stool, detected by gas chromatography-mass spectrometry (GC-MS) combined technique	3 months after discharge
Trimethylamine-N-Oxide	A metabolites of gut microbiota in plasm, quantified by stable isotope dilution liquid chromatography tandem mass spectrometry	2 days after admission
Trimethylamine-N-Oxide	A metabolites of gut microbiota in plasm, quantified by stable isotope dilution liquid chromatography tandem mass spectrometry	3 months after discharge
Untargeted Metabolomics	Untargeted metabolomics refers to using gas chromatography-mass spectrometry (GC-MS) combined technique, without bias detection of all small molecule metabolites in plasma (mainly the relative molecular weight of 1000 Da endogenous small molecule compounds) levels.	2 days after admission
Untargeted Metabolomics	Untargeted metabolomics refers to using gas chromatography-mass spectrometry (GC-MS) combined technique, without bias detection of all small molecule metabolites in plasma (mainly the relative molecular weight of 1000 Da endogenous small molecule compounds) levels.	3 months after discharge

Collaborators and Investigators

• Sponsor: Nanfang Hospital of Southern Medical University
• Collaborators: Zhujiang Hospital; First Affiliated Hospital of Jinan University; Guangdong 999 Brain Hospital

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2020
• Primary Completion (Anticipated): June 30, 2023
• Study Completion (Anticipated): June 30, 2023

Study Registration Dates

• First Submitted: December 11, 2020
• First Submitted That Met QC Criteria: December 24, 2020
• First Posted (Actual): December 29, 2020

Study Record Updates

• Last Update Posted (Actual): August 2, 2021
• Last Update Submitted That Met QC Criteria: July 29, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Keywords: Ischemic Stroke; cognitive impairment; gut microbiota
• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Necrosis; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Brain Ischemia; Cognition Disorders; Infarction; Brain Infarction; Stroke; Ischemic Stroke; Ischemia; Cognitive Dysfunction; Cerebral Infarction
• Other Study ID Numbers: NFEC-2020-169

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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