Long-term Cognitive and Cerebral Changes in Sepsis Survivors and Their Predictors
试验速览
- 阶段
- 不适用
- 发起方
- 入组人数
- 308
- 试验地点
- 4
- 主要终点
- Verbal Learning Memory Test Long Delayed Recall (Trial 7)
研究概览
简要总结
The main goals of this study are to provide a cognitive, neurological, brain morphological, and serological profile of sepsis survivors in order to make long-term prognosis of recovery and estimate the need for rehabilitation measures in order to help patients reintegrate into normal daily life.
详细描述
Comparison of cognitive function in severe septic/septic shock ICU patients with non-septic postoperative ICU patients and actively recruited healthy controls at several time points up to 12 months after leaving the ICU.
Secondary aims:
- Profiling specific cognitive deficits in sepsis survivors over time.
- Identifying possible subclasses of long-term cognitive impairment according to facets of disease, therapy and ICU experience.
- Investigating long-term brain morphological changes, with hippocampus as region of interest (ROI).
- Determining values of Serum- and CSF-Biomarkers
- Evaluation of diagnostic and prognostic value of non-routine biomarkers for systemic- and neuroinflammation in the acute phase and in the long-term
- Investigate associations between brain morphological changes, cognitive changes, neurological status, psychiatric burden, disability level, employment status and health-related quality of life (HRQOL).
- Investigating brain-activity changes in resting state electro-encephalogram (EEG)
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 25 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •sepsis/septic shock subjects will only be included in the study if they meet all of the following criteria:
- •Written informed consent of the subject. or legal representative patient at the Anesthesiological-Operative Intensive Care Unit of the University Hospital Bonn, the Department of Anesthesiology, Intensive Care and Pain Therapy of the Malteser Hospital, or the Department of Anesthesiology, Intensive Care Medicine and Pain Medicine of the Gemeinschaftskrankenhaus Bonn St. Petrus Hospital. At the Anesthesiological-Operative Intensive Care Unit of the University Hospital Bonn, only, or 1) documentation of presumed will via a relative or legal representative . together with 2) Documentation of verification by a doctor independent of the study that the patient's study participation is unobjectionable. Written informed consent of patient will be obtained at the earliest time possible.
- •Aged 25-80 years
- •Male or female
- •Admitted to the intensive care units of the Anesthesiological-Operative Intensive Care Unit of the University Hospital Bonn, from the Department of Anesthesiology, Intensive Care and Pain Therapy of the Malteser Hospital or from the Department of Anesthesiology, Intensive Care Medicine and Pain Medicine of the Gemeinschaftskrankenhaus Bonn St. Petrus Hospital.
- •Duration of ICU stay must be a minimum of 24 hours. In case of transfer to intermediate care or the observation ward before the 24 hour ICU period is complete, study parameters must be allowed to be assessed.
- •Fulfill the criteria of sepsis and/or septic shock patients according to theThird International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3, Singer et al, 2016).
- •Postoperative ICU Patients will only be included in the study if they meet all of the following criteria:
- •Written informed consent of the subject.
- •Aged 25-80 years
- •Male or female
- •Admitted to the intensive care units of the Anesthesiological-Operative Intensive Care Unit of the University Hospital Bonn, which includes a surgical ICU, an anesthesiological ICU, and a cardio-surgical ICU
- •Duration of ICU stay must be a minimum of 24 hours. In case of transfer to intermediate care or the observation ward before the 24 hour ICU period is complete, study parameters must be allowed to be assessed.
- •Mini-Mental Status Examination (MMSE) Score of 25 or above
- •Healthy Controls will only be included in the study if they meet all of the following criteria:
- •Written informed consent of the subject
- •Aged 25-80 years
- •Male or female
排除标准
- •Subjects presenting with any of the following exclusion criteria may not be included in the study:
- •Simultaneous participation in any clinical treatment study involving administration of an investigational medicinal product within 30 days prior to study beginning
- •Physical or psychiatric condition which at the investigator's discretion may put the subject at risk, may confound the study results, or may interfere with the subject's participation in this study
- •Prior to the start of this study existence of preexisting severe diseases and/or conduction of surgery necessarily imply life expectancy less than 12 months
- •Known or suspected persistent abuse of medication, drugs or alcohol now or in the past
- •Known cerebral lesions, cerebral infarction or malignomas
- •Dementia or history of other central nervous system diseases
- •Cranial-cerebral injury
- •Known HIV-Infection
- •Known liver cirrhosis with a documented Child-Pugh Score of C prior to this study
- •Liver transplants
- •Prior to start of this study nursing care level of 2 or 3
- •Prior to start of this study residing in a nursing home
- •Additional Exclusion Criteria For Non-Septic Postoperative ICU Patients:
- •Fulfill the criteria of sepsis and/or septic shock patients according to theThird International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3, Singer et al, 2016).
- •In the case that a postoperative ICU patient fulfills the criteria for sepsis during ICU stay, he/she will be moved to the sepsis group.
- •Additional Exclusion Criteria For Healthy:
- •Executing third-party cognitive and functional assessments of another patient-subject also included in this investigation
- •History of ICU stay in the last 12 months
研究组 & 干预措施
Sepsis/septic Shock
Men and women seen at the intensive care units of the Anesthesiology Department of the University Hospital Bonn aged 25-80; fulfill the criteria of sepsis and/or septic shock patients according to theThird International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3, Singer et al, 2016).
Interventions: Neurocognitive Assessment, Clinical Scales, Questionnaires, Blood Sample, voluntary Lumbar Puncture, Resting State EEG, MRI
干预措施: Blood Sample (Procedure)
Sepsis/septic Shock
Men and women seen at the intensive care units of the Anesthesiology Department of the University Hospital Bonn aged 25-80; fulfill the criteria of sepsis and/or septic shock patients according to theThird International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3, Singer et al, 2016).
Interventions: Neurocognitive Assessment, Clinical Scales, Questionnaires, Blood Sample, voluntary Lumbar Puncture, Resting State EEG, MRI
干预措施: Neurocognitive Assessment (Behavioral)
Sepsis/septic Shock
Men and women seen at the intensive care units of the Anesthesiology Department of the University Hospital Bonn aged 25-80; fulfill the criteria of sepsis and/or septic shock patients according to theThird International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3, Singer et al, 2016).
Interventions: Neurocognitive Assessment, Clinical Scales, Questionnaires, Blood Sample, voluntary Lumbar Puncture, Resting State EEG, MRI
干预措施: Resting State EEG (Other)
Sepsis/septic Shock
Men and women seen at the intensive care units of the Anesthesiology Department of the University Hospital Bonn aged 25-80; fulfill the criteria of sepsis and/or septic shock patients according to theThird International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3, Singer et al, 2016).
Interventions: Neurocognitive Assessment, Clinical Scales, Questionnaires, Blood Sample, voluntary Lumbar Puncture, Resting State EEG, MRI
干预措施: Lumbar Puncture (Procedure)
Sepsis/septic Shock
Men and women seen at the intensive care units of the Anesthesiology Department of the University Hospital Bonn aged 25-80; fulfill the criteria of sepsis and/or septic shock patients according to theThird International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3, Singer et al, 2016).
Interventions: Neurocognitive Assessment, Clinical Scales, Questionnaires, Blood Sample, voluntary Lumbar Puncture, Resting State EEG, MRI
干预措施: MRI (Other)
Postoperative ICU Patients
Men and women seen at the intensive care units of the Anesthesiology Department of the University Hospital Bonn aged 25-80:
- Admitted to the intensive care units of the Anesthesiological-Operative Intensive Care Unit of the University Hospital Bonn, which includes a surgical ICU, an anesthesiological ICU, and a cardio-surgical ICU
- Duration of ICU stay must be a minimum of 24 hours.
- Mini-Mental State Examination (MMSE) Score of 25 or above
Interventions: Neurocognitive Assessment, Clinical Scales, Questionnaires, Blood Sample, voluntary Lumbar Puncture, Resting State EEG, MRI
干预措施: Blood Sample (Procedure)
Postoperative ICU Patients
Men and women seen at the intensive care units of the Anesthesiology Department of the University Hospital Bonn aged 25-80:
- Admitted to the intensive care units of the Anesthesiological-Operative Intensive Care Unit of the University Hospital Bonn, which includes a surgical ICU, an anesthesiological ICU, and a cardio-surgical ICU
- Duration of ICU stay must be a minimum of 24 hours.
- Mini-Mental State Examination (MMSE) Score of 25 or above
Interventions: Neurocognitive Assessment, Clinical Scales, Questionnaires, Blood Sample, voluntary Lumbar Puncture, Resting State EEG, MRI
干预措施: Neurocognitive Assessment (Behavioral)
Postoperative ICU Patients
Men and women seen at the intensive care units of the Anesthesiology Department of the University Hospital Bonn aged 25-80:
- Admitted to the intensive care units of the Anesthesiological-Operative Intensive Care Unit of the University Hospital Bonn, which includes a surgical ICU, an anesthesiological ICU, and a cardio-surgical ICU
- Duration of ICU stay must be a minimum of 24 hours.
- Mini-Mental State Examination (MMSE) Score of 25 or above
Interventions: Neurocognitive Assessment, Clinical Scales, Questionnaires, Blood Sample, voluntary Lumbar Puncture, Resting State EEG, MRI
干预措施: Resting State EEG (Other)
Postoperative ICU Patients
Men and women seen at the intensive care units of the Anesthesiology Department of the University Hospital Bonn aged 25-80:
- Admitted to the intensive care units of the Anesthesiological-Operative Intensive Care Unit of the University Hospital Bonn, which includes a surgical ICU, an anesthesiological ICU, and a cardio-surgical ICU
- Duration of ICU stay must be a minimum of 24 hours.
- Mini-Mental State Examination (MMSE) Score of 25 or above
Interventions: Neurocognitive Assessment, Clinical Scales, Questionnaires, Blood Sample, voluntary Lumbar Puncture, Resting State EEG, MRI
干预措施: Lumbar Puncture (Procedure)
Postoperative ICU Patients
Men and women seen at the intensive care units of the Anesthesiology Department of the University Hospital Bonn aged 25-80:
- Admitted to the intensive care units of the Anesthesiological-Operative Intensive Care Unit of the University Hospital Bonn, which includes a surgical ICU, an anesthesiological ICU, and a cardio-surgical ICU
- Duration of ICU stay must be a minimum of 24 hours.
- Mini-Mental State Examination (MMSE) Score of 25 or above
Interventions: Neurocognitive Assessment, Clinical Scales, Questionnaires, Blood Sample, voluntary Lumbar Puncture, Resting State EEG, MRI
干预措施: MRI (Other)
Healthy Controls
Healthy Controls will only be included in the study if they meet all of the following criteria: Written informed consent of the subject, Aged 25-80 years, Male or female.
Interventions: Neurocognitive Assessment, Clinical Scales, Questionnaires, Blood Sample, voluntary Lumbar Puncture, Resting State EEG, MRI
干预措施: Blood Sample (Procedure)
Healthy Controls
Healthy Controls will only be included in the study if they meet all of the following criteria: Written informed consent of the subject, Aged 25-80 years, Male or female.
Interventions: Neurocognitive Assessment, Clinical Scales, Questionnaires, Blood Sample, voluntary Lumbar Puncture, Resting State EEG, MRI
干预措施: Neurocognitive Assessment (Behavioral)
Healthy Controls
Healthy Controls will only be included in the study if they meet all of the following criteria: Written informed consent of the subject, Aged 25-80 years, Male or female.
Interventions: Neurocognitive Assessment, Clinical Scales, Questionnaires, Blood Sample, voluntary Lumbar Puncture, Resting State EEG, MRI
干预措施: Resting State EEG (Other)
Healthy Controls
Healthy Controls will only be included in the study if they meet all of the following criteria: Written informed consent of the subject, Aged 25-80 years, Male or female.
Interventions: Neurocognitive Assessment, Clinical Scales, Questionnaires, Blood Sample, voluntary Lumbar Puncture, Resting State EEG, MRI
干预措施: Lumbar Puncture (Procedure)
Healthy Controls
Healthy Controls will only be included in the study if they meet all of the following criteria: Written informed consent of the subject, Aged 25-80 years, Male or female.
Interventions: Neurocognitive Assessment, Clinical Scales, Questionnaires, Blood Sample, voluntary Lumbar Puncture, Resting State EEG, MRI
干预措施: MRI (Other)
结局指标
主要结局
Verbal Learning Memory Test Long Delayed Recall (Trial 7)
时间窗: 6 months post ICU
Verbal Learning Memory Test Long Delayed Recall (Trial 7) at 6 months post ICU admission in sepsis/septic shock patients versus non-septic postoperative patients, and comparison to actively recruited healthy controls)
次要结局
- German Vocabulary Test(For patient groups: 12 months; for Healthy Controls: 6 months)
- Wechsler Memory Scale IV Visual Recall I and II(For patient groups: 12 months; for Healthy Controls: 6 months)
- Verbal Learning Memory Test, German Version(For patient groups: 12 months; for Healthy Controls: 6 months)
- Wechsler Memory Scale Digit-Span(For patient groups: 12 months; for Healthy Controls: 6 months)
- Trail Making Test A & B(For patient groups: 12 months; for Healthy Controls: 6 months)
- Symbol Digit Modalities Test(For patient groups: 12 months; for Healthy Controls: 6 months)
- Patient Health Questionnaire Subtests Depression, Anxiety and Somatic Symptoms(For patient groups: 12 months; for Healthy Controls: 6 months)
- Post-Traumatic Stress Syndrome 10(For patient groups: 12 months; for Healthy Controls: 6 months)
- MRI (3 Tesla) of brain with hippocampus as Region of Interest(For patient groups: 6 months, 12 months; for Healthy Controls: Baseline and 6 months)
- Lumbar Puncture (voluntary)(For Patients: (while at ICU, if clinically indicated as part of clinical routine and only if patient directly gives informed consent), 12 months; For Healthy Controls: Baseline and 6 months)
- Functional Activities Questionnaire(For patient groups: 12 months; for Healthy Controls: 6 months)
- Clinical Scales at ICU(For Patients during ICU Stay (Day 0, [Day 7 if still on ICU], Day of Release))
- Phonetic and Lexical Verbal Fluency(For patient groups: 12 months; for Healthy Controls: 6 months)
- European Quality of Life 5 Dimensions-5 Levels(For patient groups: 12 months; for Healthy Controls: 6 months)
- modified version of Rankin Scale Structured Interview (modified for ICU patients)(For patient groups: 12 months; for Healthy Controls: 6 months)
- Pittsburgh Sleep Quality Index(For patient groups: 12 months; for Healthy Controls: 6 months)
- Neurological Examination(For patient groups: 6 months, 12 months; for Healthy Controls: Baseline and 6 months)
- resting state electroencephalogram(For patient groups: 6 months, 12 months; for Healthy Controls: Baseline and 6 months)
- Mini Mental Status Examination(For patient groups: 12 months; for Healthy Controls: 6 months)
- Blood Sample(For Patient Groups 2-3 samples during ICU, 3-4 Months, 6 months, 12 Months)