The Gut Microbiome - Source of Sepsis and Novel Target in Intensive Care Units?

NCT ID: NCT06749483

Last Updated: 2024-12-30

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 100 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2024-12-27
• Study Completion Date: 2026-12-31

Brief Summary

Here, the investigators propose to study host responses to reduced microbiome complexity driven by treatment with broad spectrum antibiotics in patients with severe infections or sepsis. The proposal aims to combine holistic approaches with emerging experimental technologies to investigate the complex interactions between the gut microbiota and its host and assess the impact of specific bacterial communities on longevity and stress responses. A strong focus of this study will also be placed on microbiome dysbiosis and secondary impacts on short- and long-term brain dysfunction using clinical, laboratory and imaging procedures.

Detailed Description

Prospective observational study to obtain faeces, rectal swabs, and plasma samples from critically ill patients with and without broad spectrum antimicrobial therapy as well as from long-term survivors after sepsis. Furthermore, clinical, neuropsychological and neuroimaging data will be collected to assess short- and long-term brain dysfunction.

Furthermore it will be to correlate metagenomic and metabolomic data analysis from stool and blood samples of ICU patients with clinical outcomes (including the trajectory of neuro-cognitive deficits) and stress-related parameters.

Additionally, the study aims to identify if microbiome dysbiosis is connected to short- and long-term brain dysfunction and to assess which microbiome metabolic products influence brain dysfunction.

Moreover, the investigators aim to explore immune cell diversity through single cell whole transcriptome analysis in order to establish new hypotheses on specific bacteria species and metabolites to affect the immune cell type composition of patients (single cell immuno-profiling) and integrate single cell RNA sequencing with clinical symptoms in critically ill patients.

Finally, the question is addressed whether there are differences between blood cell composition and activation between younger and older patients with and without sepsis.

In this regard, blood- and stool samples will be taken from participants at five time points as follows: three time points during ICU treatment respectively (at study inclusion day 1, day 7 and day 14) and as well as two follow-up surveys (3 and 6 months after inclusion). Brain dysfunction will be assed by daily delirium screening tests (CAM-ICU and ICDSC) and at the time of discharge from hospital by MoCa and Mini Mental Status Examination. At the follow-up survey functional MRI as well as neuropsychological measures will be performed.

Conditions

Critical Illness; Intensive Care Unit Delirium; Neurocognitive Deficit; Microbiome,immune Function, Critically Ill; Infection in ICU; Sepsis

Keywords

sepsis; broad-spectrum antibiotics; stool; neuropsychological assessment; delirium; neurocognitive impairment; microbiome

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

ICU patients with antibiotic treatment

ICU patients treated with piperacillin/tazobactam or meropenem

No interventions assigned to this group

ICU patients without antibiotic treatment

ICU patients without antibiotic treatment during their ICU stay

No interventions assigned to this group

Long-term survivors of critical illness

Long-term survivors at least six months or more after the beginning of critical illness.

No interventions assigned to this group

Eligibility Criteria

Inclusion Criteria

• Age ≥ 18 years
• One of the following criteria

1. Critically ill patients treated with meropenem or piperacillin/tazobactam started within the last 72 h

2. Critically ill patients without systemic antimicrobial therapy within the last 72 hours and an expected ICU length of stay of more than 3 days

3. Long-term survivors of sepsis, e.g. from pre-existing sepsis cohorts

Exclusion Criteria

• Inflammatory bowel disease
• Major bowel resection
• Selective decontamination of the oral and digestive tract
• Oral vancomycin therapy
• Immunocompromised patients
• History of chemotherapy during the last 6 months.
• Known travel history to countries to areas of high antimicrobial resistance (>5% according to the report of the European Centre for Disease Prevention and Control and all countries except USA and Canada) within the last 4 weeks
• Acute neurological diseases (e.g., brain ischemia, hemorrhage, meningoencephalitis, tumor)
• Manifest dementia, pre-existing psychiatric diseases (schizophrenia, psychosis)
• Acute brain surgery
• MRI contraindications: pacemakers, hearing aids, neurostimulation, insulin pumps, other potentially ferromagnetic implants, screws, clips, prostheses, metal splinters, etc., pregnancy, claustrophobia, extensive tattoos.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Friedrich Schiller University of Jena

UNKNOWN

Sponsor Role: collaborator

Jena University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Johannes Ehler

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Johannes Ehler, Priv.-Doz. Dr. med.

Role: PRINCIPAL_INVESTIGATOR

Department of Anesthesiology and Intensive Care Medicine, Jena University Hospital

Locations

Klinik für Anästhesiologie und Intensivmedizin, Universitätsklinikum Jena

Jena, Thuringia, Germany

Site Status: RECRUITING

Countries

Germany

Central Contacts

Johannes Ehler, Priv.-Doz. Dr. med.

Role: CONTACT

Phone: +49 36419323397

Email: johannes.ehler@med.uni-jena.de

Katrin Ludewig, Dr. med.

Role: CONTACT

Phone: +49 36419323378

Email: katrin.ludewig@med.uni-jena.de

Facility Contacts

Johannes Ehler, Priv.-Doz. Dr. med.

Role: primary

Katrin Ludewig, Dr. med.

Role: backup

Johannes Ehler, Priv.-Doz. Dr. med.

Role: backup

Katrin Ludewig, Dr.med.

Role: backup

Other Identifiers

2024-3429-BO

Identifier Type: -

Identifier Source: org_study_id