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

NCT02339649 | Unknown DMC

• 2 other identifiers: BN0052011-003014-16
• Study Type: interventional
• Target: 308
• Locations: 1 country
• Sites: 2

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (34)

• Verbal Learning Memory Test, German Version

  For patient groups: 6 months; for Healthy Controls: Baseline

• 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

  For patient groups: 6 months; for Healthy Controls: Baseline

• Wechsler Memory Scale IV Visual Recall I and II

  For patient groups: 12 months; for Healthy Controls: 6 months

• Wechsler Memory Scale Digit-Span

  For patient groups: 6 months; for Healthy Controls: Baseline

Study Arms (3)

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

Procedure: Blood Sample; Behavioral: Neurocognitive Assessment; Other: Resting State EEG; Procedure: Lumbar Puncture; Other: 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: * 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

Procedure: Blood Sample; Behavioral: Neurocognitive Assessment; Other: Resting State EEG; Procedure: Lumbar Puncture; Other: 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

Procedure: Blood Sample; Behavioral: Neurocognitive Assessment; Other: Resting State EEG; Procedure: Lumbar Puncture; Other: MRI

Interventions

Blood Sample PROCEDURE

Blood Sample

Healthy Controls; Postoperative ICU Patients; Sepsis/septic Shock

Neurocognitive Assessment BEHAVIORAL

Neurocognitive Assessment

Healthy Controls; Postoperative ICU Patients; Sepsis/septic Shock

Resting State EEG OTHER

10-20 Minutes of Resting State EEG

Also known as: Resting-State EEG

Healthy Controls; Postoperative ICU Patients; Sepsis/septic Shock

Lumbar Puncture PROCEDURE

Lumbar Puncture

Healthy Controls; Postoperative ICU Patients; Sepsis/septic Shock

MRI OTHER

60 Minutes MRI

Healthy Controls; Postoperative ICU Patients; Sepsis/septic Shock

Eligibility Criteria

• Age: 25 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:

You may not qualify if:

• 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
• 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.
• Executing third-party cognitive and functional assessments of another patient-subject also included in this investigation

Sponsors & Collaborators

• German Center for Neurodegenerative Diseases (DZNE): lead
• University Hospital, Bonn: collaborator

Study Sites (2)

DZNE Center for Clinical Research

Bonn, North Rhine-Westphalia, 53117, Germany

NOT YET RECRUITING

Department of Anesthesiology, University Hospital Bonn

Bonn, North Rhine-Westphalia (nrw), 53105, Germany

RECRUITING

Related Publications (8)

• 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.

  PMID: 19906966 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.

  PMID: 24088092 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.

  PMID: 23134661 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.

  PMID: 23718252 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.

  PMID: 20978258 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.

  PMID: 24849863 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.

  PMID: 25231518 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.

  PMID: 24724819 BACKGROUND

Related Links

• German Center for Neurodegenerative Disease (DZNE)
• Department of Anesthesiology, University Hospital Bonn

MeSH Terms

Conditions

Sepsis; Shock, Septic

Interventions

Blood Specimen Collection; Mental Status and Dementia Tests; Spinal Puncture

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques; Neuropsychological Tests; Psychological Tests; Behavioral Disciplines and Activities; Biopsy; Diagnostic Techniques, Neurological; Therapeutics

Study Officials

• 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

• 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

Central Study Contacts

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

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 3, 2011
• First Posted: January 15, 2015
• Study Start: September 1, 2013
• Primary Completion: October 1, 2017
• Study Completion: October 1, 2019
• Last Updated: August 1, 2017

Record last verified: 2017-07

Data Sharing

• IPD Sharing: Will not share

Locations

DE (2)