Trial document




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  DRKS00000735

Trial Description

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Title

Neurological sequelae and changes in nociception after severe sepsis or septic shock

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Trial Acronym

NeuroPain

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URL of the Trial

[---]*

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Brief Summary in Lay Language

There is only a small number of studies aiming at long-term consequences of severe sepsis and septic shock. However, recent results indicate cognitive and functional impairments, decrements in Health related Quality of life (HRQoL) and increased levels of pain even years in the aftermath of sepsis. Substantial efforts have been made to improve the diagnosis and therapy of sepsis, leading to a reduced mortality within the near future. As more and more patients will survive sepsis, it becomes increasingly important to investigate the long-term consequences of sepsis.
Experimental and clinical data suggest a close relationship between the activation of the immune system and increased pain perception. Sepsis is defined as massive inflammtion and could result in acute and chronic alterations of the pain processing. Within 2 years HRQoL and pain will be measured by questionnaires. To identify specific changes in pain processing, detection- and pain-thresholds for several thermal and tactile-mechanic stimuli will be collected by quantitative sensory testing (QST). Additionally the functioning of nociceptive fibers will be tested via laser-stimulation of small skin areas of the hand.
Moreover, the extent of cognitive consequences of sepsis-survivors is not yet known. These cognitive impairments could be caused by septic encephalopathy, which occurs in approximately 50% of all sepsis-patients and may be the result of changes in the nervous system. To describe these changes, patients will undergo several neuropsychological verbal, non-verbal and visual tests. The main variables are different memory functions and spatial or temporal information of brain waves evoked after visual stimulation. Brain waves will be measured with the modalities of electroencephalography (EEG) or magnetoencephalography (MEG). With this kind of data, a differentiation between basic sensory deficits and disturbances in higher mental processes should be possible.
To identify sepsis-specific consequences, results will be compared to non-septic intensive care patients, patients with hepatic encephalopathy and healthy controls.

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Brief Summary in Scientific Language

Different studies revealed long-term impairments in the health-related quality of life (HRQoL) of sepsis-survivors. This could be a result of constant cognitive and functional impairments in the aftermath of sepsis. Moreover, results of experimental and clinical studies suggest a close relationship between the activation of the immune system and increased pain perception.
To quantify physical and psychosocial impairments, HRQoL will be measured by the SF-12 (ICU-discharge, „visit 1“) and SF-36 (all other assessments/ „visits“). To assess the patient's subjective pain perception and functional interference with daily living the DSF (Deutscher Schmerzfragebogen) questionnaire will be administered. Furthermore, patients will undergo quantitative sensory testing (QST) to examine peripheral and/or central sensitization-processes. In addition, laser-evoked fields (MEG) and laser-evoked potentials (EEG) will be measured to study differentially central Aδ- and C-fiber activity.
Our second aim is to identify neurophysiological parameters of cerebral (dys-) function and selected cognitive functions after Sepsis with magnetoencephalography (MEG) and electroencephalography (EEG). These measures will take place after ICU-discharge, 6 and 12 months after acute illness, respectively. Main object of investigation are oscillatory processes as neurophysiological correlate of basic information-processing and markers of higher cogntive activity, i.e. visual attention or memory. Additionally, visual-perceptive functions and short-time memory (via critical-flicker-frequency and several memory tests) will be assessed. Thus, residual neurocognitive symptoms after recoovery from severe sepsis or septic shock with or without septic encephalopathy and their neurophysiological mechanisms after incomplete recovery is the primary concern.
Again, results will be compared with healthy controls and patients with hepatic encephalopathy. The findings of our study might have important implications for the diagnosis and treatment of septic patients in the future.

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Organizational Data

  •   DRKS00000735
  •   2011/03/21
  •   [---]*
  •   yes
  •   Approved
  •   2969-11/10, 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 septicaemia
  •   R57.2 -  [generalization R57: Shock, not elsewhere classified]
  •   K72.7 -  [generalization K72: Hepatic failure, not elsewhere classified]
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Interventions/Observational Groups

  •   No interventions, solely the observation of the following parameters in septic patients (Number = 120):

    Measurements will take place at the time of ICU discharge (with only a subgroup of 20 patients), as well as 6, 12 and 24 month after ICU discharge, respectively:
    - Edinburgh Handedness Inventory: one-time assessment of handedness
    - Detection of premorbid as well as actual cognitive abilities by means of the DemTect and the Informant Questionnaire on Cognitive Decline in Elderly (IQCODE)
    - Quantification of the health-related quality of life by means of the SF12 (ICU discharge) and SF36 (at the time of all consecutive measurements).
    - Comprehensive quantification of the patient's pain perception and functional interference with daily living by means of the DSF questionnaire (Deutscher Schmerzfragebogen)
    - Quantitative sensory testing (QST) to assess perception and pain thresholds as well as
    peripheral and/or central sensitization processes
    In a subgroup of 20 patients:
    - Assessment of the activity of central Aδ- and C-fibers by means of laser evoked (EEG) potentials and fields (MEG)
    Moreover, in a subgroup of 25 former sepsis patients (Measurements will take place at the time of ICU discharge, as well as 6 and 12 months after ICU discharge)
    - Measurement of cerebral oscillations during resting, during a memory task and during visual stimulation with flickering pictures in EEG and MEG
    - Behavioural data will be collected during a recognition test, the Verbal Learning Memory Test (VLMT) and the Corsi Block Tapping Test
    - Assessment of the critical flicker frequency by means of the Schuhfried FLIM test
  •   No interventions, solely the observation of the following parameters in former non-septic ICU patients (Number = 120):

    Measurements will take place at the time of ICU discharge (only a subgroup of 20 Patients), 6, 12 and 24 months after ICU discharge, respectively.

    - Edinburgh Handedness Inventory: one-time assessment of handedness
    - Detection of premorbid and actual cognitive abilities by means of the DemTect and the Informant Questionnaire on Cognitive Decline in Elderly (IQCODE)
    - Quantification of the health-related quality of life by means of the SF12 (ICU discharge) and SF36 (at the time of all consecutive measurements) .
    - Comprehensive quantification of the patient's pain perception and interference with daily living by means of the DSF questionnaire (Deutscher Schmerzfragebogen)
    - Quantitative sensory testing (QST) to assess perception and pain thresholds as well as
    peripheral and/or central sensitization processes
    In a subgroup of 20 patients:
    - Assessment of activity of central Aδ- and C-fibers by means of laser evoked potentials (EEG) and fields (MEG)
  •   No interventions, solely the observation of the following parameters in patients with hepatic encephalopathy

    Measurements will take place during hospitalization and 6 and 12 month after hospitalization, respectively.
    - Detection of premorbid and actual cognitive abilities by means the Informant Questionnaire on Cognitive Decline in Elderly (IQCODE)
    - Measurement of cerebral oscillations during resting, during a memory task and during visual stimulation with flickering pictures in EEG and MEG
    - Behavioural data will be collected during a recognition test, the Verbal Learning Memory Test (VLMT) and the Corsi Block Tapping Test
    - Assessment of the critical Flicker frequency by means of the Schuhfried FLIM test
  •   No interventions, solely the observation of the following parameters in healthy controls

    Measurements will take place 3 times with an interval of 6 months, respectively:

    - Measurement of cerebral oscillations during resting, during a memory task and during visual stimulation with flickering pictures in EEG and MEG
    - Behavioural data will be collected during a recognitions test, the Verbal learning memory test (VLMT) and the Corsi Block Tapping test
    - Assessment of the critical Flicker frequency by means of the Schuhfried FLIM test

    These measurements will take place only two times with an interval of 6 months:

    - Edinburgh Handedness Inventory: one-time assessment of handedness
    - Detection of premorbid and actual cognitive abilities by means of the DemTect and the Informant Questionnaire on Cognitive Decline in Elderly (IQCODE)
    - Quantification of the health-related quality of life by means of the SF12 (ICU discharge) and SF36 (consecutive measurements).
    - Comprehensive quantification of pain perception and interference with daily living by means of the DSF questionnaire (Deutscher Schmerzfragebogen)
    - Quantitative sensory testing (QST) to assess perception and pain thresholds as well as peripheric and / or central sensitization processes
    In a subgroup of 20 patients:
    - Assessment of activity of central Aδ- and C-fibers by means of laser evoked potentials (EEG) and fields (MEG)
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Characteristics

  •   Non-interventional
  •   Other
  •   Non-randomized controlled trial
  •   Open (masking not used)
  •   [---]*
  •   Other
  •   Diagnostic
  •   Other
  •   [---]*
  •   [---]*
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Primary Outcome

Primary goals (12 month after ICU discharge):
a) evaluation of chronic pain, functional impairment and the quality of life in former septic patients in comparison to non-septic ICU patients and healty controls
b) Identifications of neurophysiological mechanisms and behavioural correlates after severe sepsis/ septic shock

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Secondary Outcome

Secondary goals (range from discharge up to 24 months after discharge)
a) assessment of neurophysiological characteristics of pain processing by means of quantitative sensory testing (QST) and the laser - stimulation of Aδ- and C-Fibers at the time of ICU discharge, as well as 6, 12 ad 24 months after ICU discharge
b) identification of neurophysiological differences/ similarities of sepsis survivors and patients with hepatic encephalopathy

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Countries of Recruitment

  •   Germany
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Locations of Recruitment

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Recruitment

  •   Actual
  •   2011/04/27
  •   120
  •   Monocenter trial
  •   National
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Inclusion Criteria

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

Common inclusion criteria (all participants):
Minimum age: 18; informed consent, sufficient skills in German language;
Sepsis specific: Maximum age: 85, survivors of severe sepsis/ septic shock; duration of mechanical ventilation ≥ 3 days in ICU;
non septic ICU patients: Maximum age: 85;duration of mechanical ventilation ≥ 3 days in ICU;
HE sepcific: Maximum age: 65; confirmed diagnosis of liver failure (sonographic, CT, histological); HE-grade 0-2,
Control specific: Maximum Age for neurological examinations: 65 and 85 years for pain examinations

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Exclusion Criteria

common exclusion criteria (for all participants):
Participation in a different study; confirmed diagnosis of dementia or other severe neurological disorder (epilepsy included); seizure, confirmed septic shock or severe sepsis in anamnesis; recent drug abuse and/ or alcohol intoxication
sepsis specific: medication with analgetics; Amputation of upper limbs; confirmed chronic or other neuropathic pain disorder;
additionally for neurological examinations (25 patients): Medication with neuroleptics, sedatives, antidepressants, Amaurosis
non-septic ICU patients: ICU stay due to sepsis or septic shock; medication with analgetics; Amputation of upper limbs; confirmed chronic or other neuropathic pain disorder;
HE-specific: Medication with neuroleptics, sedatives, antidepressants, Amaurosis; life expectancy < 1 year; spontaneous bacterial peritonitis; actual delir and/ or deprivation; liver transplantation
control specific: medication with analgetics, amputation of the upper limbs; confirmed confirmed chronic or other neuropathic pain disorder; medication with neuroleptics, sedatives, antidepressants, Amaurosis;
MEG and MRI-sepcific: pace maker and other magnetic implants; claustrophobics; pregnancy

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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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    • Klinik für Anästhesiologie und Intensivtherapie; Universitätsklinikum der FSU Jena
    • Mr.  PD Dr. med.   Winfried   Meissner 
    • Erlanger Allee 101
    • 07747  Jena
    • Germany
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    • Hans-Berger-Klinik für Neurologie Universitätsklinikum der FSU Jena
    • Mr.  Dr. med.   Albrecht   Günther 
    • 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
    • Hannoversche Straße 28-30
    • 10115   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.