The Gut Microbiome - Source of Sepsis and Novel Target in Intensive Care Units? Research on Human Tissue, Body Fluids, Neuropsychological Assessment and Brain Imaging
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 100
- 试验地点
- 1
- 主要终点
- Number of patients with brain dysfunction
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥ 18 years
- •One of the following criteria
- •Critically ill patients treated with meropenem or piperacillin/tazobactam started within the last 72 h
- •Critically ill patients without systemic antimicrobial therapy within the last 72 hours and an expected ICU length of stay of more than 3 days
- •Long-term survivors of sepsis, e.g. from pre-existing sepsis cohorts
排除标准
- •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.
结局指标
主要结局
Number of patients with brain dysfunction
时间窗: From enrollment to day 180
Patients from all three groups will be assessed for microbiome dysbiosis (e.g. shotgun metagenomics), and for brain dysfunction (e.g. CAM-ICU, ICDSC, MoCa, MMST, neuropsychiatric examination, MRI).
次要结局
- Number of patients with survival(From enrollment to the end of study at 180 days)
- Days on the ICU(From enrollment to the end of study at 180 days)
- Days on the respirator(From enrollment to the end of study at 180 days)
- Days with vasopressor support(From enrollment to the end of study at 180 days)
研究者
Johannes Ehler
Principal Investigator
Jena University Hospital