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Long-term Cognitive and Cerebral Changes in Sepsis Survivors and Their Predictors (BonSEP)

Primary Purpose

Severe Sepsis With Septic Shock, Severe Sepsis Without Septic Shock

Status
Unknown status
Phase
Not Applicable
Locations
Germany
Study Type
Interventional
Intervention
Blood Sample
Neurocognitive Assessment
Resting State EEG
Lumbar Puncture
MRI
Sponsored by
German Center for Neurodegenerative Diseases (DZNE)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for Severe Sepsis With Septic Shock focused on measuring sepsis, septic shock, ICU, long-term outcome, neurocognitive, inflammatory, MRI, EEG, brain imaging, serum biomarkers, CSF

Eligibility Criteria

25 Years - 80 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

INCLUSION CRITERIA:

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

EXCLUSION CRITERIA:

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

Sites / Locations

  • Department of Anesthesiology, University Hospital BonnRecruiting
  • DZNE Center for Clinical Research

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Other

Other

Other

Arm Label

Sepsis/septic Shock

Postoperative ICU Patients

Healthy Controls

Arm Description

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

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 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

Outcomes

Primary Outcome Measures

Verbal Learning Memory Test Long Delayed Recall (Trial 7)
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

Verbal Learning Memory Test, German Version
Verbal Learning and Memory: Verbal Learning Memory Test, German Version
Verbal Learning Memory Test, German Version
Verbal Learning and Memory: Verbal Learning Memory Test, German Version
Wechsler Memory Scale IV Visual Recall I and II
Visual Memory: Wechsler Memory Scale IV Visual Recall I and II
Wechsler Memory Scale IV Visual Recall I and II
Visual Memory: Wechsler Memory Scale IV Visual Recall I and II
Wechsler Memory Scale Digit-Span
Working Memory: Wechsler Memory Scale Digit-Span
Wechsler Memory Scale Digit-Span
Working Memory: Wechsler Memory Scale Digit-Span
German Vocabulary Test
Premorbid Verbal Ability: German Vocabulary Test Mehrfachwahl Wortschatztest B (MWT-B)
German Vocabulary Test
Premorbid Verbal Ability: German Vocabulary Test
Symbol Digit Modalities Test
Cognitive Speed
Symbol Digit Modalities Test
Cognitive Speed
Trail Making Test A & B
Simple and Divided Attention
Trail Making Test A & B
Simple and Divided Attention
Phonetic and Lexical Verbal Fluency
Phonetic and Lexical Verbal Fluency
Phonetic and Lexical Verbal Fluency
Phonetic and Lexical Verbal Fluency
Patient Health Questionnaire Subtests Depression, Anxiety and Somatic Symptoms
Depression and Anxiety Inventory
Patient Health Questionnaire Subtests Depression, Anxiety and Somatic Symptoms
Depression and Anxiety Inventory
Post-Traumatic Stress Syndrome 10
Post-Traumatic Stress Screening
Post-Traumatic Stress Syndrome 10
Post-Traumatic Stress Screening
European Quality of Life 5 Dimensions-5 Levels
Quality of Life
European Quality of Life 5 Dimensions-5 Levels
Quality of Life
Functional Activities Questionnaire
Activities of Daily Living
Functional Activities Questionnaire
Activities of Daily Living
modified version of Rankin Scale Structured Interview (modified for ICU patients)
Function Scale
modified version of Rankin Scale Structured Interview (modified for ICU patients)
Function Scale
Pittsburgh Sleep Quality Index
Sleep Quality
Pittsburgh Sleep Quality Index
Sleep Quality
Mini Mental Status Examination
Cognitive Screening
Mini Mental Status Examination
Cognitive Screening
Clinical Scales at ICU
Therapeutic Intervention Scoring System-10, Total Score Simplified Acute Physiology Score, Sequential Organ Failure Assessment Confusion Assessment Method for the ICU
Neurological Examination
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
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.
MRI (3 Tesla) of brain with hippocampus as Region of Interest
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
Blood Sample
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.
Lumbar Puncture (voluntary)
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

Full Information

First Posted
August 3, 2011
Last Updated
July 28, 2017
Sponsor
German Center for Neurodegenerative Diseases (DZNE)
Collaborators
University Hospital, Bonn
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1. Study Identification

Unique Protocol Identification Number
NCT02339649
Brief Title
Long-term Cognitive and Cerebral Changes in Sepsis Survivors and Their Predictors
Acronym
BonSEP
Official Title
Long-term Cognitive and Cerebral Changes in Sepsis Survivors and Their Predictors
Study Type
Interventional

2. Study Status

Record Verification Date
July 2017
Overall Recruitment Status
Unknown status
Study Start Date
September 2013 (undefined)
Primary Completion Date
October 2017 (Anticipated)
Study Completion Date
October 2019 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
German Center for Neurodegenerative Diseases (DZNE)
Collaborators
University Hospital, Bonn

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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)

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Severe Sepsis With Septic Shock, Severe Sepsis Without Septic Shock
Keywords
sepsis, septic shock, ICU, long-term outcome, neurocognitive, inflammatory, MRI, EEG, brain imaging, serum biomarkers, CSF

7. Study Design

Primary Purpose
Other
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
Outcomes Assessor
Allocation
Non-Randomized
Enrollment
308 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Sepsis/septic Shock
Arm Type
Other
Arm Description
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
Arm Title
Postoperative ICU Patients
Arm Type
Other
Arm Description
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
Arm Title
Healthy Controls
Arm Type
Other
Arm Description
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
Intervention Type
Procedure
Intervention Name(s)
Blood Sample
Intervention Description
Blood Sample
Intervention Type
Behavioral
Intervention Name(s)
Neurocognitive Assessment
Intervention Description
Neurocognitive Assessment
Intervention Type
Other
Intervention Name(s)
Resting State EEG
Other Intervention Name(s)
Resting-State EEG
Intervention Description
10-20 Minutes of Resting State EEG
Intervention Type
Procedure
Intervention Name(s)
Lumbar Puncture
Intervention Description
Lumbar Puncture
Intervention Type
Other
Intervention Name(s)
MRI
Intervention Description
60 Minutes MRI
Primary Outcome Measure Information:
Title
Verbal Learning Memory Test Long Delayed Recall (Trial 7)
Description
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)
Time Frame
6 months post ICU
Secondary Outcome Measure Information:
Title
Verbal Learning Memory Test, German Version
Description
Verbal Learning and Memory: Verbal Learning Memory Test, German Version
Time Frame
For patient groups: 6 months; for Healthy Controls: Baseline
Title
Verbal Learning Memory Test, German Version
Description
Verbal Learning and Memory: Verbal Learning Memory Test, German Version
Time Frame
For patient groups: 12 months; for Healthy Controls: 6 months
Title
Wechsler Memory Scale IV Visual Recall I and II
Description
Visual Memory: Wechsler Memory Scale IV Visual Recall I and II
Time Frame
For patient groups: 6 months; for Healthy Controls: Baseline
Title
Wechsler Memory Scale IV Visual Recall I and II
Description
Visual Memory: Wechsler Memory Scale IV Visual Recall I and II
Time Frame
For patient groups: 12 months; for Healthy Controls: 6 months
Title
Wechsler Memory Scale Digit-Span
Description
Working Memory: Wechsler Memory Scale Digit-Span
Time Frame
For patient groups: 6 months; for Healthy Controls: Baseline
Title
Wechsler Memory Scale Digit-Span
Description
Working Memory: Wechsler Memory Scale Digit-Span
Time Frame
For patient groups: 12 months; for Healthy Controls: 6 months
Title
German Vocabulary Test
Description
Premorbid Verbal Ability: German Vocabulary Test Mehrfachwahl Wortschatztest B (MWT-B)
Time Frame
For patient groups: 6 months; for Healthy Controls: Baseline
Title
German Vocabulary Test
Description
Premorbid Verbal Ability: German Vocabulary Test
Time Frame
For patient groups: 12 months; for Healthy Controls: 6 months
Title
Symbol Digit Modalities Test
Description
Cognitive Speed
Time Frame
For patient groups: 6 months; for Healthy Controls: Baseline
Title
Symbol Digit Modalities Test
Description
Cognitive Speed
Time Frame
For patient groups: 12 months; for Healthy Controls: 6 months
Title
Trail Making Test A & B
Description
Simple and Divided Attention
Time Frame
For patient groups: 6 months; for Healthy Controls: Baseline
Title
Trail Making Test A & B
Description
Simple and Divided Attention
Time Frame
For patient groups: 12 months; for Healthy Controls: 6 months
Title
Phonetic and Lexical Verbal Fluency
Description
Phonetic and Lexical Verbal Fluency
Time Frame
For patient groups: 6 months; for Healthy Controls: Baseline
Title
Phonetic and Lexical Verbal Fluency
Description
Phonetic and Lexical Verbal Fluency
Time Frame
For patient groups: 12 months; for Healthy Controls: 6 months
Title
Patient Health Questionnaire Subtests Depression, Anxiety and Somatic Symptoms
Description
Depression and Anxiety Inventory
Time Frame
For patient groups: 6 months; for Healthy Controls: Baseline
Title
Patient Health Questionnaire Subtests Depression, Anxiety and Somatic Symptoms
Description
Depression and Anxiety Inventory
Time Frame
For patient groups: 12 months; for Healthy Controls: 6 months
Title
Post-Traumatic Stress Syndrome 10
Description
Post-Traumatic Stress Screening
Time Frame
For patient groups: 6 months; for Healthy Controls: Baseline
Title
Post-Traumatic Stress Syndrome 10
Description
Post-Traumatic Stress Screening
Time Frame
For patient groups: 12 months; for Healthy Controls: 6 months
Title
European Quality of Life 5 Dimensions-5 Levels
Description
Quality of Life
Time Frame
For patient groups: 6 months; for Healthy Controls: Baseline
Title
European Quality of Life 5 Dimensions-5 Levels
Description
Quality of Life
Time Frame
For patient groups: 12 months; for Healthy Controls: 6 months
Title
Functional Activities Questionnaire
Description
Activities of Daily Living
Time Frame
For patient groups: 6 months; for Healthy Controls: Baseline
Title
Functional Activities Questionnaire
Description
Activities of Daily Living
Time Frame
For patient groups: 12 months; for Healthy Controls: 6 months
Title
modified version of Rankin Scale Structured Interview (modified for ICU patients)
Description
Function Scale
Time Frame
For patient groups: 6 months; for Healthy Controls: Baseline
Title
modified version of Rankin Scale Structured Interview (modified for ICU patients)
Description
Function Scale
Time Frame
For patient groups: 12 months; for Healthy Controls: 6 months
Title
Pittsburgh Sleep Quality Index
Description
Sleep Quality
Time Frame
For patient groups: 6 months; for Healthy Controls: Baseline
Title
Pittsburgh Sleep Quality Index
Description
Sleep Quality
Time Frame
For patient groups: 12 months; for Healthy Controls: 6 months
Title
Mini Mental Status Examination
Description
Cognitive Screening
Time Frame
For patient groups: (OP Probands 1-28 d before OP, 6 months; for Healthy Controls: Baseline
Title
Mini Mental Status Examination
Description
Cognitive Screening
Time Frame
For patient groups: 12 months; for Healthy Controls: 6 months
Title
Clinical Scales at ICU
Description
Therapeutic Intervention Scoring System-10, Total Score Simplified Acute Physiology Score, Sequential Organ Failure Assessment Confusion Assessment Method for the ICU
Time Frame
For Patients during ICU Stay (Day 0, [Day 7 if still on ICU], Day of Release)
Title
Neurological Examination
Description
Subscales Motor ability, Walking and Standing, Behavior, Praxis/Visual or Visuospatial, Speaking and Language, Autonomic Nervous System, Tone and Muscle Exam, Coordination and Movement
Time Frame
For patient groups: 6 months, 12 months; for Healthy Controls: Baseline and 6 months
Title
resting state electroencephalogram
Description
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.
Time Frame
For patient groups: 6 months, 12 months; for Healthy Controls: Baseline and 6 months
Title
MRI (3 Tesla) of brain with hippocampus as Region of Interest
Description
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
Time Frame
For patient groups: 6 months, 12 months; for Healthy Controls: Baseline and 6 months
Title
Blood Sample
Description
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.
Time Frame
For Patient Groups 2-3 samples during ICU, 3-4 Months, 6 months, 12 Months
Title
Lumbar Puncture (voluntary)
Description
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
Time Frame
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
25 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
INCLUSION CRITERIA: 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 EXCLUSION CRITERIA: 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Catherine N. Widmann, M.A.
Phone
+49 (0)228 287 13093
Email
catherine.widmann@dzne.de
First Name & Middle Initial & Last Name or Official Title & Degree
Michael T. Heneka, MD
Phone
+49 (0)228 287 13091
Email
michael.heneka@dzne.de
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Michael T Heneka, M.D.
Organizational Affiliation
German Center for Neurodegenerative Diseases (DZNE)
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Andreas Hoeft, M.D.
Organizational Affiliation
Department of Anesthesiology and Intensive Care Medicine, University Hospital Bonn
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Christian Putensen, M.D.
Organizational Affiliation
Research Unit Pulmonary Dysfunction and Sepsis, Department of Anesthesiology and Intensive Care Medicine, University Hospital Bonn
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Thomas Klockgether, M.D.
Organizational Affiliation
German Center for Neurodegenerative Diseases (DZNE)
Official's Role
Study Chair
Facility Information:
Facility Name
Department of Anesthesiology, University Hospital Bonn
City
Bonn
State/Province
North Rhine-Westphalia (NRW)
ZIP/Postal Code
53105
Country
Germany
Individual Site Status
Recruiting
Facility Name
DZNE Center for Clinical Research
City
Bonn
State/Province
Northrhine-Westphalia
ZIP/Postal Code
53117
Country
Germany
Individual Site Status
Not yet recruiting

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
19906966
Citation
Weberpals M, Hermes M, Hermann S, Kummer MP, Terwel D, Semmler A, Berger M, Schafers M, Heneka MT. NOS2 gene deficiency protects from sepsis-induced long-term cognitive deficits. J Neurosci. 2009 Nov 11;29(45):14177-84. doi: 10.1523/JNEUROSCI.3238-09.2009.
Results Reference
background
PubMed Identifier
24088092
Citation
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Links:
URL
http://www.dzne.de
Description
German Center for Neurodegenerative Disease (DZNE)
URL
http://www.henekalab.com
Description
Clinical Neuroscience Unit, Department of Neurology, University Hospital Bonn
URL
http://www.kai.uni-bonn.de/
Description
Department of Anesthesiology, University Hospital Bonn

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Long-term Cognitive and Cerebral Changes in Sepsis Survivors and Their Predictors

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