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

NCT ID: NCT02339649

Last Updated: 2017-08-01

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

NA

Total Enrollment

308 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-09-30

Study Completion Date

2019-10-31

Brief Summary

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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.

Detailed Description

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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)

Conditions

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Severe Sepsis With Septic Shock Severe Sepsis Without Septic Shock

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

OTHER

Blinding Strategy

SINGLE

Outcome Assessors

Study Groups

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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

Group Type OTHER

Blood Sample

Intervention Type PROCEDURE

Blood Sample

Neurocognitive Assessment

Intervention Type BEHAVIORAL

Neurocognitive Assessment

Resting State EEG

Intervention Type OTHER

10-20 Minutes of Resting State EEG

Lumbar Puncture

Intervention Type PROCEDURE

Lumbar Puncture

MRI

Intervention Type OTHER

60 Minutes MRI

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

Group Type OTHER

Blood Sample

Intervention Type PROCEDURE

Blood Sample

Neurocognitive Assessment

Intervention Type BEHAVIORAL

Neurocognitive Assessment

Resting State EEG

Intervention Type OTHER

10-20 Minutes of Resting State EEG

Lumbar Puncture

Intervention Type PROCEDURE

Lumbar Puncture

MRI

Intervention Type OTHER

60 Minutes MRI

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

Group Type OTHER

Blood Sample

Intervention Type PROCEDURE

Blood Sample

Neurocognitive Assessment

Intervention Type BEHAVIORAL

Neurocognitive Assessment

Resting State EEG

Intervention Type OTHER

10-20 Minutes of Resting State EEG

Lumbar Puncture

Intervention Type PROCEDURE

Lumbar Puncture

MRI

Intervention Type OTHER

60 Minutes MRI

Interventions

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Blood Sample

Blood Sample

Intervention Type PROCEDURE

Neurocognitive Assessment

Neurocognitive Assessment

Intervention Type BEHAVIORAL

Resting State EEG

10-20 Minutes of Resting State EEG

Intervention Type OTHER

Lumbar Puncture

Lumbar Puncture

Intervention Type PROCEDURE

MRI

60 Minutes MRI

Intervention Type OTHER

Other Intervention Names

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Resting-State EEG

Eligibility Criteria

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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:

* 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

* 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
* History of ICU stay in the last 12 months
Minimum Eligible Age

25 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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University Hospital, Bonn

OTHER

Sponsor Role collaborator

German Center for Neurodegenerative Diseases (DZNE)

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Michael T Heneka, M.D.

Role: PRINCIPAL_INVESTIGATOR

German Center for Neurodegenerative Diseases (DZNE)

Andreas Hoeft, M.D.

Role: STUDY_CHAIR

Department of Anesthesiology and Intensive Care Medicine, University Hospital Bonn

Christian Putensen, M.D.

Role: STUDY_CHAIR

Research Unit Pulmonary Dysfunction and Sepsis, Department of Anesthesiology and Intensive Care Medicine, University Hospital Bonn

Thomas Klockgether, M.D.

Role: STUDY_CHAIR

German Center for Neurodegenerative Diseases (DZNE)

Locations

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DZNE Center for Clinical Research

Bonn, North Rhine-Westphalia, Germany

Site Status NOT_YET_RECRUITING

Department of Anesthesiology, University Hospital Bonn

Bonn, North Rhine-Westphalia (nrw), Germany

Site Status RECRUITING

Countries

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Germany

Central Contacts

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Catherine N. Widmann, M.A.

Role: CONTACT

+49 (0)228 287 13093

Michael T. Heneka, MD

Role: CONTACT

+49 (0)228 287 13091

References

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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.

Reference Type BACKGROUND
PMID: 19906966 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 24088092 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 23134661 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 23718252 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 20978258 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 24849863 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25231518 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 24724819 (View on PubMed)

Related Links

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http://www.dzne.de

German Center for Neurodegenerative Disease (DZNE)

http://www.kai.uni-bonn.de/

Department of Anesthesiology, University Hospital Bonn

Other Identifiers

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2011-003014-16

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

BN005

Identifier Type: -

Identifier Source: org_study_id

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