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| ID | Type | Description | Link |
|---|---|---|---|
| 2011-003014-16 | EudraCT Number |
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| Name | Class |
|---|---|
| University Hospital, Bonn | OTHER |
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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.
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:
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Sepsis/septic Shock | Other | 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 | Other | Men and women seen at the intensive care units of the Anesthesiology Department of the University Hospital Bonn aged 25-80:
Interventions: Neurocognitive Assessment, Clinical Scales, Questionnaires, Blood Sample, voluntary Lumbar Puncture, Resting State EEG, MRI |
|
| Healthy Controls | Other | 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 |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Blood Sample | Procedure | Blood Sample |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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) | 6 months post ICU |
| Measure | Description | Time Frame |
|---|---|---|
| Verbal Learning Memory Test, German Version | Verbal Learning and Memory: Verbal Learning Memory Test, German Version | For patient groups: 6 months; for Healthy Controls: Baseline |
| Verbal Learning Memory Test, German Version |
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INCLUSION CRITERIA:
sepsis/septic shock subjects will only be included in the study if they meet all of the following criteria:
Postoperative ICU Patients will only be included in the study if they meet all of the following criteria:
Healthy Controls will only be included in the study if they meet all of the following criteria:
EXCLUSION CRITERIA:
Subjects presenting with any of the following exclusion criteria may not be included in the study:
Additional Exclusion Criteria For Non-Septic Postoperative ICU Patients:
Additional Exclusion Criteria For Healthy:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Catherine N. Widmann, M.A. | Contact | +49 (0)228 287 13093 | catherine.widmann@dzne.de | |
| Michael T. Heneka, MD | Contact | +49 (0)228 287 13091 | michael.heneka@dzne.de |
| Name | Affiliation | Role |
|---|---|---|
| Michael T Heneka, M.D. | German Center for Neurodegenerative Diseases (DZNE) | Principal Investigator |
| Andreas Hoeft, M.D. | Department of Anesthesiology and Intensive Care Medicine, University Hospital Bonn | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| DZNE Center for Clinical Research | Not yet recruiting | Bonn | North Rhine-Westphalia | 53117 | Germany | |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 19906966 | Background | 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. | |
| 24088092 | Background | Pandharipande PP, Girard TD, Jackson JC, Morandi A, Thompson JL, Pun BT, Brummel NE, Hughes CG, Vasilevskis EE, Shintani AK, Moons KG, Geevarghese SK, Canonico A, Hopkins RO, Bernard GR, Dittus RS, Ely EW; BRAIN-ICU Study Investigators. Long-term cognitive impairment after critical illness. N Engl J Med. 2013 Oct 3;369(14):1306-16. doi: 10.1056/NEJMoa1301372. |
| Label | URL |
|---|---|
| German Center for Neurodegenerative Disease (DZNE) | View source |
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| Neurocognitive Assessment | Behavioral | Neurocognitive Assessment |
|
| Resting State EEG | Other | 10-20 Minutes of Resting State EEG |
|
|
| Lumbar Puncture | Procedure | Lumbar Puncture |
|
| MRI | Other | 60 Minutes MRI |
|
Verbal Learning and Memory: Verbal Learning Memory Test, German Version
| For patient groups: 12 months; for Healthy Controls: 6 months |
| Wechsler Memory Scale IV Visual Recall I and II | Visual Memory: Wechsler Memory Scale IV Visual Recall I and II | For patient groups: 6 months; for Healthy Controls: Baseline |
| Wechsler Memory Scale IV Visual Recall I and II | Visual Memory: Wechsler Memory Scale IV Visual Recall I and II | For patient groups: 12 months; for Healthy Controls: 6 months |
| Wechsler Memory Scale Digit-Span | Working Memory: Wechsler Memory Scale Digit-Span | For patient groups: 6 months; for Healthy Controls: Baseline |
| Wechsler Memory Scale Digit-Span | Working Memory: Wechsler Memory Scale Digit-Span | For patient groups: 12 months; for Healthy Controls: 6 months |
| German Vocabulary Test | Premorbid Verbal Ability: German Vocabulary Test Mehrfachwahl Wortschatztest B (MWT-B) | For patient groups: 6 months; for Healthy Controls: Baseline |
| German Vocabulary Test | Premorbid Verbal Ability: German Vocabulary Test | For patient groups: 12 months; for Healthy Controls: 6 months |
| Symbol Digit Modalities Test | Cognitive Speed | For patient groups: 6 months; for Healthy Controls: Baseline |
| Symbol Digit Modalities Test | Cognitive Speed | For patient groups: 12 months; for Healthy Controls: 6 months |
| Trail Making Test A & B | Simple and Divided Attention | For patient groups: 6 months; for Healthy Controls: Baseline |
| Trail Making Test A & B | Simple and Divided Attention | For patient groups: 12 months; for Healthy Controls: 6 months |
| Phonetic and Lexical Verbal Fluency | Phonetic and Lexical Verbal Fluency | For patient groups: 6 months; for Healthy Controls: Baseline |
| Phonetic and Lexical Verbal Fluency | Phonetic and Lexical Verbal Fluency | For patient groups: 12 months; for Healthy Controls: 6 months |
| Patient Health Questionnaire Subtests Depression, Anxiety and Somatic Symptoms | Depression and Anxiety Inventory | For patient groups: 6 months; for Healthy Controls: Baseline |
| Patient Health Questionnaire Subtests Depression, Anxiety and Somatic Symptoms | Depression and Anxiety Inventory | For patient groups: 12 months; for Healthy Controls: 6 months |
| Post-Traumatic Stress Syndrome 10 | Post-Traumatic Stress Screening | For patient groups: 6 months; for Healthy Controls: Baseline |
| Post-Traumatic Stress Syndrome 10 | Post-Traumatic Stress Screening | For patient groups: 12 months; for Healthy Controls: 6 months |
| European Quality of Life 5 Dimensions-5 Levels | Quality of Life | For patient groups: 6 months; for Healthy Controls: Baseline |
| European Quality of Life 5 Dimensions-5 Levels | Quality of Life | For patient groups: 12 months; for Healthy Controls: 6 months |
| Functional Activities Questionnaire | Activities of Daily Living | For patient groups: 6 months; for Healthy Controls: Baseline |
| Functional Activities Questionnaire | Activities of Daily Living | For patient groups: 12 months; for Healthy Controls: 6 months |
| modified version of Rankin Scale Structured Interview (modified for ICU patients) | Function Scale | For patient groups: 6 months; for Healthy Controls: Baseline |
| modified version of Rankin Scale Structured Interview (modified for ICU patients) | Function Scale | For patient groups: 12 months; for Healthy Controls: 6 months |
| Pittsburgh Sleep Quality Index | Sleep Quality | For patient groups: 6 months; for Healthy Controls: Baseline |
| Pittsburgh Sleep Quality Index | Sleep Quality | For patient groups: 12 months; for Healthy Controls: 6 months |
| Mini Mental Status Examination | Cognitive Screening | For patient groups: (OP Probands 1-28 d before OP, 6 months; for Healthy Controls: Baseline |
| Mini Mental Status Examination | Cognitive Screening | For patient groups: 12 months; for Healthy Controls: 6 months |
| 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 | For Patients during ICU Stay (Day 0, [Day 7 if still on ICU], Day of Release) |
| 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 | For patient groups: 6 months, 12 months; for Healthy Controls: Baseline and 6 months |
| 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. | 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 | 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 | For patient groups: 6 months, 12 months; for Healthy Controls: Baseline and 6 months |
| 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. | For Patient Groups 2-3 samples during ICU, 3-4 Months, 6 months, 12 Months |
| 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 | 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 |
| Christian Putensen, M.D. | Research Unit Pulmonary Dysfunction and Sepsis, Department of Anesthesiology and Intensive Care Medicine, University Hospital Bonn | Study Chair |
| Thomas Klockgether, M.D. | German Center for Neurodegenerative Diseases (DZNE) | Study Chair |
| Department of Anesthesiology, University Hospital Bonn |
| Recruiting |
| Bonn |
| North Rhine-Westphalia (nrw) |
| 53105 |
| Germany |
| 23134661 | Background | Semmler A, Widmann CN, Okulla T, Urbach H, Kaiser M, Widman G, Mormann F, Weide J, Fliessbach K, Hoeft A, Jessen F, Putensen C, Heneka MT. Persistent cognitive impairment, hippocampal atrophy and EEG changes in sepsis survivors. J Neurol Neurosurg Psychiatry. 2013 Jan;84(1):62-9. doi: 10.1136/jnnp-2012-302883. Epub 2012 Nov 7. |
| 23718252 | Background | Sonneville R, Verdonk F, Rauturier C, Klein IF, Wolff M, Annane D, Chretien F, Sharshar T. Understanding brain dysfunction in sepsis. Ann Intensive Care. 2013 May 29;3(1):15. doi: 10.1186/2110-5820-3-15. |
| 20978258 | Background | Iwashyna TJ, Ely EW, Smith DM, Langa KM. Long-term cognitive impairment and functional disability among survivors of severe sepsis. JAMA. 2010 Oct 27;304(16):1787-94. doi: 10.1001/jama.2010.1553. |
| 24849863 | Background | Widmann CN, Heneka MT. Long-term cerebral consequences of sepsis. Lancet Neurol. 2014 Jun;13(6):630-6. doi: 10.1016/S1474-4422(14)70017-1. |
| 25231518 | Background | Widmann CN, Schewe JC, Heneka MT. Sepsis-associated encephalopathy versus sepsis-induced encephalopathy--authors' reply. Lancet Neurol. 2014 Oct;13(10):968-9. doi: 10.1016/S1474-4422(14)70204-2. No abstract available. |
| 24724819 | Background | Lindlau A, Widmann CN, Putensen C, Jessen F, Semmler A, Heneka MT. Predictors of hippocampal atrophy in critically ill patients. Eur J Neurol. 2015 Feb;22(2):410-5. doi: 10.1111/ene.12443. Epub 2014 Apr 12. |
| Department of Anesthesiology, University Hospital Bonn | View source |
| ID | Term |
|---|---|
| D018805 | Sepsis |
| D012772 | Shock, Septic |
| ID | Term |
|---|---|
| D007239 | Infections |
| D018746 | Systemic Inflammatory Response Syndrome |
| D007249 | Inflammation |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D012769 | Shock |
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| ID | Term |
|---|---|
| D001800 | Blood Specimen Collection |
| D000073216 | Mental Status and Dementia Tests |
| D013129 | Spinal Puncture |
| ID | Term |
|---|---|
| D013048 | Specimen Handling |
| D019411 | Clinical Laboratory Techniques |
| D019937 | Diagnostic Techniques and Procedures |
| D003933 | Diagnosis |
| D011677 | Punctures |
| D013514 | Surgical Procedures, Operative |
| D008919 | Investigative Techniques |
| D009483 | Neuropsychological Tests |
| D011581 | Psychological Tests |
| D004191 | Behavioral Disciplines and Activities |
| D001706 | Biopsy |
| D003943 | Diagnostic Techniques, Neurological |
| D013812 | Therapeutics |
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