Trial document





This trial has been registered retrospectively.
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  DRKS00005484

Trial Description

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Title

Long-term sequelae after severe sepsis: cognitive impairments and structural changes in the brain, an MRI study

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Trial Acronym

LossCog-MRI

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URL of the Trial

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Brief Summary in Lay Language

Currently, research on blood poisoning (sepsis) is focused on improving survival rates. However, information on both death rate and symptoms is required to evaluate a reliable effect of therapy. International self-help groups such as the North American ARDS Foundation (http://www.ardsusa.org/) or the German Sepsis Aid (GSA; http://www.deutsche-sepsis-hilfe.or/) focus more on long-term sequelae and health-related quality of life (HRQoL) of an intervention. A sufficiently long observation period for studies in sepsis patients and HRQoL assessment is recommended. The number of patients with mental decline after sepsis is high and the impairment they experience is often severe. However, the extent of patients' post sepsis mental and physical limitations is still incompletely understood. In LOSS-Cog MRI, we aim to investigate the underlying neurophysiological mechanisms of sepsis-induced mental impairment.
In this regard, progress has been achieved by results from two projects from the Center for Sepsis Control and Care (CSCC). Firstly, a slowdown and decoupling of brain function after sepsis in combination with impaired mental abilities was found. Secondly, septic rats exhibited a reduction of certain brain structures. To test our hypotheses about the mechanisms underlying the described alterations, the project will specifically analyze whether the decent modifications are related to a real damage of brain regions, or rather to a disturbance of the functional interaction between different brain regions.
Different tests (MRI, magnetoencephalograpy = MEG and cognitive behavioral tests) are going to be conducted with sepsis survivors and normal, healthy controls.

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Brief Summary in Scientific Language

The focus of sepsis research is currently on improving survival rates. However, information on both mortality and morbidity is required to evaluate the net effect of therapy. International self-help groups such as the North American ARDS Foundation (http://www.ardsusa.org/) or the German Sepsis Aid (GSA; http://www.deutsche-sepsis-hilfe.or/) focus more on long-term sequelae and health-related quality of life (HRQoL) of an intervention. In line with this, the European Medicines Agency (EMA) guidelines CHMP/EWP/4713/03 recommend a sufficiently long observation period for studies in sepsis patients and HRQoL assessment. The number of patients with cognitive decline after sepsis is high and the impairment they experience is often severe (Iwashyna et al., 2010). However, the extent of patients' post sepsis cognitive and functional limitations is still incompletely understood. In LOSS-Cog MRI, we aim to investigate the underlying neurophysiological mechanisms of sepsis-induced cognitive impairment.
In this regard, progress has been achieved by results from two projects in the Center for Sepsis Control and Care (Jena). Firstly, a desynchronization of brain function after sepsis in combination with impaired cognitive function and secondly, a reduction in size of the amygdala in septic rats was reported. To test our hypotheses about the mechanisms underlying the described alterations, the project will specifically analyze whether the decent modifications are related to the damage of fibers connecting different brain regions, or rather to a disturbance of the functional interaction between different brain regions.

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Organizational Data

  •   DRKS00005484
  •   2013/12/12
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  •   yes
  •   Approved
  •   3853-08/13, Ethikkommission der Friedrich-Schiller-Universität Jena an der Medizinischen Fakultät
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Secondary IDs

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Health Condition or Problem studied

  •   A41 -  Other sepsis
  •   R57.2 -  Septic shock
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Interventions/Observational Groups

  •   Sepsis-survivors:
    Cognitive Testing: a) DemTect and Clock drawing test; b) Verbal Learning and Memory Test (VLMT, Helmstaedter, Lendt und Lux, Beltz Test GmbH, Göttingen 2001) declarative verbal memory (learning and long-term encoding and retrieval); c) Testbatterie für Aufmerksamkeitsprüfung (TAP), Alertness: tonic alertness, maintenance of a high level of reaction and capacity over a long time, Go/No-Go: suppression of unwanted reactions, split attention: simultaneous execution of a visual and auditory task
    MRI: anatomical T1-scan of the brain; atrophies/ changes in brain volumes, resting state, fMRI
    MEG: resting activity with eyes open/ closed (hallmark for global brain function); frequency entrainment characterized by the global similarity index (GSI); measure for the synchronization of brain regions
  •   Healthy controls:
    Cognitive Testing: a) DemTect and Clock drawing test; b) Verbal Learning and Memory Test (VLMT, Helmstaedter, Lendt und Lux, Beltz Test GmbH, Göttingen 2001) declarative verbal memory (learning and long-term encoding and retrieval); c) Testbatterie für Aufmerksamkeitsprüfung (TAP), Alertness: tonic alertness, maintenance of a high level of reaction and capacity over a long time, Go/No-Go: suppression of unwanted reactions, split attention: simultaneous execution of a visual and auditory task
    MRI: anatomical T1-scan of the brain; atrophies/ changes in brain volumes, resting state, fMRI
    MEG: resting activity with eyes open/ closed (hallmark for global brain function); frequency entrainment characterized by the global similarity index (GSI); measure for the synchronization of brain regions
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Characteristics

  •   Non-interventional
  •   Other
  •   Non-randomized controlled trial
  •   Open (masking not used)
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  •   Other
  •   Basic research/physiological study
  •   Parallel
  •   N/A
  •   N/A
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Primary Outcome

characterization of structural changes in the brain via fractional anisotropy; voxel based morphometry of the amygdala/ hippocampus

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Secondary Outcome

Correlation between cognitive outcomes (TAP/ DemTect) and MEG parameters; Structural changes in the brain in terms of fiber damages; change of functional connectivity in former sepsis patients

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Countries of Recruitment

  •   Germany
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Locations of Recruitment

  • University Medical Center 
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Recruitment

  •   Actual
  •   2013/09/01
  •   50
  •   Monocenter trial
  •   National
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Inclusion Criteria

  •   Both, male and female
  •   18   Years
  •   65   Years
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Additional Inclusion Criteria

Sepsis patients:
Survivors of severe sepsis/ septic shock; male and female adults aged between 18-65 years; Written informed consent; former sepsis patients with an IQCODE > 2,29; Former sepsis patients who requested help of the German Sepsis Aid between 2011 and 2013
Normal healthy controls:
male and female adults aged between 18-65 years; Written informed consent

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Exclusion Criteria

stroke or other severe CNS disorders; epilepsy; cardiac pacemaker, defibrillator and other electromagnetic devices; Liver cirrhosis; amaurosis; current intake of neuroleptics/ antidepressants; acute claustrophobia; pregnancy; participation in another study

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Addresses

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    • Integriertes Forschungs- und Behandlungszentrum (IFB) Sepsis und Sepsisfolgen: Center for Sepsis Control and Care (CSCC); Universitätsklinikum Jena
    • Erlanger Allee 101
    • 07747  Jena
    • Germany
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    •   +49 3641 9323376
    •   49 3641 9323382
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    • Deutsche Sepsis-Hilfe e.V.
    • Ms.  Ariane  Viller 
    • Erlanger Allee 101
    • 07749  Jena
    • Germany
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    • Hans-Berger-Klinik für Neurologie Universitätsklinikum Jena
    • Ms.  Dr.  Theresa  Götz 
    • Erlanger Allee 101
    • 07747  Jena
    • Germany
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    • Hans-Berger-Klinik für Neurologie Universitätsklinikum Jena
    • Ms.  Dr.  Theresa  Götz 
    • Erlanger Allee 101
    • 07747  Jena
    • Germany
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Sources of Monetary or Material Support

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    • Bundesministerium für Bildung und Forschung Dienstsitz Berlin
    • Friedrichstraße 130 B
    • 10117  Berlin
    • Germany
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Status

  •   Recruiting ongoing
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Trial Publications, Results and other Documents

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* This entry means the parameter is not applicable or has not been set.