Long-term Cognitive and Cerebral Changes in Sepsis Survivors and Their Predictors
- Conditions
- Severe Sepsis With Septic ShockSevere Sepsis Without Septic Shock
- Interventions
- Procedure: Blood SampleBehavioral: Neurocognitive AssessmentOther: Resting State EEGProcedure: Lumbar PunctureOther: MRI
- Registration Number
- NCT02339649
- Lead Sponsor
- German Center for Neurodegenerative Diseases (DZNE)
- Brief Summary
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.
- Detailed Description
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)
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 308
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Postoperative ICU Patients Resting State EEG 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 Healthy Controls Neurocognitive Assessment 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 Healthy Controls Resting State EEG 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 Sepsis/septic Shock Blood Sample 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 Postoperative ICU Patients MRI 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 Healthy Controls MRI 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 Sepsis/septic Shock Resting State EEG 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 Sepsis/septic Shock MRI 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 Postoperative ICU Patients Lumbar Puncture 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 Healthy Controls Blood Sample 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 Sepsis/septic Shock Neurocognitive Assessment 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 Sepsis/septic Shock Lumbar Puncture 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 Postoperative ICU Patients Blood Sample 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 Postoperative ICU Patients Neurocognitive Assessment 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 Healthy Controls Lumbar Puncture 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
- Primary Outcome Measures
Name Time Method Verbal Learning Memory Test Long Delayed Recall (Trial 7) 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)
- Secondary Outcome Measures
Name Time Method German Vocabulary Test For patient groups: 12 months; for Healthy Controls: 6 months Premorbid Verbal Ability: German Vocabulary Test
Wechsler Memory Scale IV Visual Recall I and II For patient groups: 12 months; for Healthy Controls: 6 months Visual Memory: Wechsler Memory Scale IV Visual Recall I and II
Verbal Learning Memory Test, German Version For patient groups: 12 months; for Healthy Controls: 6 months Verbal Learning and Memory: Verbal Learning Memory Test, German Version
Wechsler Memory Scale Digit-Span For patient groups: 12 months; for Healthy Controls: 6 months Working Memory: Wechsler Memory Scale Digit-Span
Symbol Digit Modalities Test For patient groups: 12 months; for Healthy Controls: 6 months Cognitive Speed
Trail Making Test A & B For patient groups: 12 months; for Healthy Controls: 6 months Simple and Divided Attention
Patient Health Questionnaire Subtests Depression, Anxiety and Somatic Symptoms For patient groups: 12 months; for Healthy Controls: 6 months Depression and Anxiety Inventory
Post-Traumatic Stress Syndrome 10 For patient groups: 12 months; for Healthy Controls: 6 months Post-Traumatic Stress Screening
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 MRI (3 Tesla) of brain with hippocampus as Region of Interest. Protocol includes: three-dimensional, T1-weighted rapid gradient echo sequence, Resting State, Gradient Echo-Field-Map for Resting State, Inversion Recovery Echo Planar Imaging for Resting State, Spoiled Gradient Echo, Fluid Attenuated inversion Recovery, Susceptibility weighted imaging, Diffusion Tensor Imaging, Gradient Echo-Field-Map for Diffusion Tensor Imaging
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 Cerebrospinal fluid (CSF) routine parameters will be analyzed by the Central Laboratory. Results will then be provided to the investigator. For determination of τ, phospho-τ, β-amyloid 1 40 and β-amyloid 1 42, 5 ml of cerebral-spinal-fluid will be analyzed at the laboratories of the German Center for Neurodegenerative Diseases (DZNE), Biomarker Dementia Working Group, Sigmund-Freud-Str. 25, 53105 Bonn
Functional Activities Questionnaire For patient groups: 12 months; for Healthy Controls: 6 months Activities of Daily Living
Clinical Scales at ICU For Patients during ICU Stay (Day 0, [Day 7 if still on ICU], Day of Release) Therapeutic Intervention Scoring System-10, Total Score Simplified Acute Physiology Score, Sequential Organ Failure Assessment Confusion Assessment Method for the ICU
Phonetic and Lexical Verbal Fluency For patient groups: 12 months; for Healthy Controls: 6 months Phonetic and Lexical Verbal Fluency
European Quality of Life 5 Dimensions-5 Levels For patient groups: 12 months; for Healthy Controls: 6 months Quality of Life
modified version of Rankin Scale Structured Interview (modified for ICU patients) For patient groups: 12 months; for Healthy Controls: 6 months Function Scale
Pittsburgh Sleep Quality Index For patient groups: 12 months; for Healthy Controls: 6 months Sleep Quality
Neurological Examination For patient groups: 6 months, 12 months; for Healthy Controls: Baseline and 6 months Subscales Motor ability, Walking and Standing, Behavior, Praxis/Visual or Visuospatial, Speaking and Language, Autonomic Nervous System, Tone and Muscle Exam, Coordination and Movement
resting state electroencephalogram For patient groups: 6 months, 12 months; for Healthy Controls: Baseline and 6 months 10-20 system electroencephalogram (64 channels with additional electro-oculogram, electromyogram, electrocardiogram). The protocol includes 5 phases, each one minute long: 1) eyes open, relaxed state, fixation of a black dot at 2 m distance, 2) word generation using letter "P" with eyes closed, 3) mental arithmetic: continuous subtraction of 7 starting from 1,000 with eyes closed, 4) eyes closed, relaxed state, no task, 5) visualization of a previously memorized geometric figure with eyes closed. Data sampled at a rate of 256 Herz using an anti-aliasing low pass filter. Power spectra will be calculated for consecutive 4-second windows and calculated for each electrode contact. Absolute spectral power will be determined for the delta (0.5-4 Herz), theta (4-8 Herz), alpha (8-13 Herz), beta (13-20 Herz) and gamma (20-40 Herz) bands, which will be averaged across all windows.
Mini Mental Status Examination For patient groups: 12 months; for Healthy Controls: 6 months Cognitive Screening
Blood Sample For Patient Groups 2-3 samples during ICU, 3-4 Months, 6 months, 12 Months All blood samples shall be drawn, stored and analyzed according to the participant information in the laboratories of the Biomarker Dementia Working Group and the Central Laboratory. Blood sampling analysis will include leukocyte count, hemoglobin, hematocrit, erythrocytes, Mean Corpuscular Hemoglobin, Meam Corpuscular Volume, mean Corpuscular Hemoglobin Concentration, Thrombocytes, Glucose, Lactate, electrolytes Sodium, Potassium, Calcium, Cholesterine, Tumor necrosis Factor-alpha, Interleukin-1 alpha, Interleukin-1 beta, Interleukin-6, C-reactive protein, Neuron Specific Enolase, Procalcitonin, S-100 Protein, as well as DNA and serum biorepository for further scientific analysis.
Trial Locations
- Locations (2)
Department of Anesthesiology, University Hospital Bonn
🇩🇪Bonn, North Rhine-Westphalia (NRW), Germany
DZNE Center for Clinical Research
🇩🇪Bonn, Northrhine-Westphalia, Germany