<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT02265263</url>
  </required_header>
  <id_info>
    <org_study_id>BioCog</org_study_id>
    <nct_id>NCT02265263</nct_id>
  </id_info>
  <brief_title>Biomarker Development for Postoperative Cognitive Impairment in the Elderly (BioCog)</brief_title>
  <acronym>BioCog</acronym>
  <official_title>Biomarker Development for Postoperative Cognitive Impairment in the Elderly (BioCog)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Charite University, Berlin, Germany</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>European Union</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Charite University, Berlin, Germany</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The research leading consortium to these results has received funding from the European Union&#xD;
      Seventh Framework Programme [FP7/2007-2013] under grant agreement no 602461 (www.biocog.eu).&#xD;
&#xD;
      The investigators will establish valid biomarkers panels (neuroimaging and molecular) for&#xD;
      risk and clinical outcome prediction of postoperative delirium (POD)/postoperative cognitive&#xD;
      deficit (POCD) in elective surgical patients (Age ≥ 65 years) in study centers in&#xD;
      Berlin,Germany (data collection within 2 years after initial hospital stay) and Utrecht, The&#xD;
      Netherlands (data collection within 1 year after initial hospital stay), thereof&#xD;
      cerebrospinal fluid (only once on day of surgery in patients with planned spinal&#xD;
      anesthesia/combined spinal epidural analgesia in patients, only in Berlin).&#xD;
&#xD;
      A control group of ASA II/III- patients is collected for measuring the learning experience&#xD;
      during the cognitive testings. The participants are matched on age, education, and gender to&#xD;
      the study patients. The ASA II/III- control patients receive additionally MRI-scan (3 Tesla)&#xD;
      at baseline, after 3 months and after 1 (Utrecht) and 2 years (Berlin).&#xD;
&#xD;
      To analyze scanner variability we additionally measure at maximum 20 subjects (Age ≥ 65&#xD;
      years, ASA I and II) from Utrecht in the MRI scanner (3-Tesla) in Berlin and vice versa.&#xD;
&#xD;
      A study group at maximum (n= 80) and is collected for measuring 7 Tesla MRI at two timepoints&#xD;
      (Baseline and 90 days).The primary endponit of this substudy is gamma amino-butyric acid&#xD;
      concentration in CNS after 3-months (measured by MRI). A retrospective comparison group&#xD;
      (extracting 8000 intensive care unit patient data from the patient data management system&#xD;
      during the BioCog study period in 2016) to analyse economic effects that are caused by the&#xD;
      implementation of quality indicators in health care.&#xD;
&#xD;
      An interim-analysis is performed on the primary endpoint after 400 included patients.&#xD;
&#xD;
      The resulting (multivariate) expert system is expected: 1) to support clinical&#xD;
      decision-making in patient care, e.g. to balance the individual POD/POCD risk against the&#xD;
      expected overall clinical outcome of an (elective) surgical intervention, 2) to allow the&#xD;
      design of more sophisticated and hypothesis-driven clinical studies and drug trials&#xD;
      (translational research) in the future. The latter will be possible on the basis of&#xD;
      biomarker-based sub-grouping of patients and a better understanding of relevant&#xD;
      pathophysiological processes.&#xD;
&#xD;
      Furthermore, a state-of-the art clinical database and biobank will be created that does not&#xD;
      yet exist worldwide. Both the expert system and the reference database/biobank will expand&#xD;
      the leadership of the contributing academic institutions in this particular research area. In&#xD;
      addition, the newly created biobank will become an integral part of the European Biobanking&#xD;
      and Biomolecular Resources Research Infrastructure (BBMRI) which allows top address specific&#xD;
      and hypothesis-driven research questions.&#xD;
&#xD;
      Most notably, the developed (multivariate) expert system also has the potential for&#xD;
      commercialization. Possible customers are: 1) physicians and hospital departments being&#xD;
      involved in pre-surgical decision making, 2) pharmaceutical industry intending to conduct&#xD;
      biomarker-based drug trials in POD/POCD.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Terminated</overall_status>
  <start_date type="Actual">October 2014</start_date>
  <completion_date type="Actual">June 2019</completion_date>
  <primary_completion_date type="Actual">December 2017</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Incidence of Delirium</measure>
    <time_frame>Participants will be followed for the duration of hospital stay, an expected average of 7 days</time_frame>
    <description>Postoperative delirium rate, defined according to Diagnostic and Statistical Manual of Mental Disorders (DSM-V) and/or as ≥ 2 cumulative points in the nursing Delirium Screening Scale (Nu-DESC) and/or a positive Confusion Assessment Method (CAM) and/or Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) score and/or patient chart review that shows descriptions of delirium.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence of postoperative cognitive deficit (POCD)</measure>
    <time_frame>Up to 3 months after the operation</time_frame>
    <description>POCD will be measured by a defined Cambridge Neuropsychological Test Automated Battery (CANTAB) POCD will be measured by a defined Cambridge Neuropsychological Test Automated Battery (CANTAB) and paper pencil tests (TMT A und B, Grooved Pegboard) and the Mini - Mental State Examination (MMSE)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Duration of Delirium</measure>
    <time_frame>Participants will be followed for the duration of hospital stay, an exspected average of 7 days</time_frame>
    <description>Diagnostic and Statistical Manual of Mental Disorders (DSM-V)&#xD;
Nursing Delirium Screening Scale (Nu-DESC)&#xD;
Intensive Care Delirium Screening Checklist (ICDSC)&#xD;
Delirium Detection Scale (DDS)&#xD;
Confusion Assessment Method for the Intensive Care Unit (CAM-ICU)&#xD;
Confusion Assessment Method (CAM)&#xD;
Chart Review</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of subsyndromal postoperative delirium</measure>
    <time_frame>Participants will be followed for the duration of hospital stay, an exspected average of 7 days</time_frame>
    <description>Nu-DESC score 1 and/or any criteria suggestive of POD (as described under &quot;Primary Outcome Measures&quot;) that do not fulfill DSM-5 criteria for delirium.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of subsyndromal postoperative delirium</measure>
    <time_frame>Participants will be followed for the duration of hospital stay, an exspected average of 7 days</time_frame>
    <description>Nu-DESC score 1 and/or any criteria suggestive of POD (as described under &quot;Primary Outcome Measures&quot;) that do not fulfill DSM-5 criteria for Delirium</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Intensive care unit length of stay</measure>
    <time_frame>Participants will be followed for the duration of intensive care unit stay, an expected average of 5 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hospital length of stay</measure>
    <time_frame>Participants will be followed for the duration of hospital stay, an exspected average of 7 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Postoperative organ complications</measure>
    <time_frame>Participants will be followed for the duration of hospital stay, an exspected average of 7 days</time_frame>
    <description>Postoperative organ complications are classified according to Clavien - Dindo classification.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of postoperative cognitive deficit</measure>
    <time_frame>1 year, 2 years, 5 years after the operation</time_frame>
    <description>POCD will be measured by a defined Cambridge Neuropsychological Test Automated Battery (CANTAB), paper pencil tests (TMT A und B, Grooved Pegboard) and the Mini - Mental State Examination (MMSE)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Socioeconomic characteristics</measure>
    <time_frame>3 months, 1, 2 and 5 years after the operation</time_frame>
    <description>Study center Berlin: Health economic data according to cost of patient care (The §21 dataset (diagnoses and operation-codes). Hospital costs are calculated according to the Institute for the Hospital Remuneration System (InEK) calculation scheme to compare the refinanced costs in each cost category/cost-center segment from study center Charité. Necessity and indirect costs of medical care (outpatient visits) after hospital stay.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Health related quality of life</measure>
    <time_frame>3 months, 1, 2 and 5 years after the operation</time_frame>
    <description>Study center Berlin: Measurement by EQ-5D</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Barthel Index</measure>
    <time_frame>3 months, 1, 2 and 5 years after the operation</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Instrumental activities of daily living scale</measure>
    <time_frame>3 months, 1, 2 and 5 years after the operation</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hand grip strength test</measure>
    <time_frame>3 months, 1, 2 and 5 years after the operation</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Malnutrition</measure>
    <time_frame>3 months, 1, 2 and 5 years after the operation</time_frame>
    <description>Mini Nutritional Assessment - Short form, Serum albumin</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mobility</measure>
    <time_frame>3 months, 1, 2 and 5 years after the operation</time_frame>
    <description>Timed up and go test</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Neuroimaging Biomarker</measure>
    <time_frame>3 months, 1, 2 and 5 years after the operation</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Molecular Biomarker</measure>
    <time_frame>3 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Health related Quality of life</measure>
    <time_frame>3 months, 1 year after the operation</time_frame>
    <description>Study center Utrecht: Measurement by EQ-5D</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Socioeconomic characteristics</measure>
    <time_frame>3 months, 1 year after the operation</time_frame>
    <description>Study center Utrecht: Health economic data according to direct cost of patient care (inpatient and outpatient stays) and necessity and indirect costs of medical care (outpatient visits) after hospital stay.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Heart rate variability</measure>
    <time_frame>Study center Berlin: Participants will be followed for the duration of hospital stay, an exspected average of 7 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Light Levels (lux)</measure>
    <time_frame>Study center Berlin: Participants will be followed for the duration of hospital stay, an exspected average of 7 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Light frequencies</measure>
    <time_frame>Study center Berlin: Participants will be followed for the duration of hospital stay, an exspected average of 7 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Depression</measure>
    <time_frame>Participants will be followed for the duration of hospital stay, an exspected average of 7 days</time_frame>
    <description>Hospital Anxiety and Depression Scale (HADS) (Study Center Utrecht), GDS-15 (Study Center Berlin)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Anxiety</measure>
    <time_frame>Participants will be followed for the duration of hospital stay, an exspected average of 7 days</time_frame>
    <description>Faces Anxiety Scale (FAS)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Electroencephalography (EEG)- Mapping</measure>
    <time_frame>At time of surgery</time_frame>
    <description>Study center Berlin: EEG with19 electrodes and hypo- and hyperventilation in physiological limits (no patients with neurological pre-existing conditions or proposed neuro-surgery)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mortality</measure>
    <time_frame>3 months, 1, 2 and 5 years after the operation</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Depth of consciousness index</measure>
    <time_frame>At time of surgery</time_frame>
    <description>Depth of consciousness index measured by processive Electroencephalography and Electromyography (EEG/EMG) -Data (SedLine®)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Intraoperative cerebral oxymetry</measure>
    <time_frame>At time of surgery</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes of Electroencephalography</measure>
    <time_frame>Participants will be followed up until the end of postanesthesia care unit, an exspected average of 2 days</time_frame>
    <description>Signals are measured by EEG Monitor and Delir Monitor software</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Depth of sedation</measure>
    <time_frame>At time of surgery and Participants will be followed for the duration of intensive care unit stay, an expected average of 5 days</time_frame>
    <description>Intraoperatively: Observe´s Assessment of Alertness/Sedation scale (OAA/S) and postoperatievly: Richmond Agitation Sedation Scale (RASS)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pain Scales</measure>
    <time_frame>3 months</time_frame>
    <description>Perioperatively: Pain sensitivity questionnare; Pain Catastrophing Scale (PCS-GE)(PSQ); Numerische Rating Scale (NRS-V); Behavioural Pain Scale (BPS for ventilated) and BPS-NI (for non-ventilated) patients, Critical-Care Pain Observation Tool (CPOT); Rotterdam Elderly Pain Observation Scale (REPOS); Pupillometry by Neurolight; Intraoperatively: Measurement of the nociceptive flexion reflex threshold (Dolosys Paintracker); Measurement of the pupillary dilation reflex threshold (AlgiScan); Automatic collection of the data of the medication pumps; Multiple blood analysis to measure the plasma-concentrations of anesthetics; Automatic collection of the data of the SED-Line-EEG-Monitor.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality indicators of intensive care unit</measure>
    <time_frame>Participants will be followed for the duration of intensive care unit stay, an expected average of 5 days</time_frame>
    <description>Study Center Berlin: This endpoint aims to analyse economic effects of the prospective study patients and retrospective control subjects in the intensive care unit that are caused by the implementation of quality indicators in health care.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Glucosevariability</measure>
    <time_frame>At time of surgery and Participants will be followed for the duration of intensive care unit stay, an expected average of 5 days</time_frame>
    <description>Measured by Continuous Glucose Monitoring System</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Frailty</measure>
    <time_frame>3 months, 1, 2 and 5 years after the operation</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Coagulationdisorder of the blood</measure>
    <time_frame>3 months</time_frame>
    <description>Kidney marker</description>
  </secondary_outcome>
  <number_of_groups>4</number_of_groups>
  <enrollment type="Actual">1054</enrollment>
  <condition>Postoperative Delirium (POD)</condition>
  <condition>Postoperative Cognitive Deficit (POCD)</condition>
  <arm_group>
    <arm_group_label>Surgical patients - 3 Tesla MRI</arm_group_label>
    <description>A study group of at maximum n= 1200 is collected for measuring 3 Tesla MRI at two timepoints (Baseline and 90 days) in Berlin/Utrecht. They include surgical procedures within body cavity e.g. abdomen or thorax from departments of general surgery, urology, gynecology or thoracic surgery; orthopaedic operations (hip-, knee-, endoprosthesis or spine (including neurosurgical spine operations)); cardiac surgery and operation of extracranial/intracranial head and neck&#xD;
Data collection from study center Utrecht ist within one year after initial hospital stay. Data collection from study center Berlin is within two years after initial hospital stay.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Patients ASA II/III - 3 Tesla MRI</arm_group_label>
    <description>A control group of at maximum n= 300 ASA II/III- patients is collected for measuring the learning experience during the cognitive testings. They are matched on age, education, and gender to the study patients. The 104 ASA II/III- patients should receive additionally MRI-scan (3 Tesla) at baseline, after 3 months and after 1 year in Utrecht, after 3 months, after 1, 2 years in Berlin.&#xD;
Data collection from study center Utrecht ist within one year after initial hospital stay. Data collection from study center Berlin is within five years after initial hospital stay.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Volunteers ASA I/II - 3 Tesla MRI</arm_group_label>
    <description>To analyze scanner variability we additionally measure at maximum 20 subjects (Age ≥ 65 years) from Utrecht in the MRI scanner (3-Tesla) in Berlin and vice versa.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Surgical patients - 7 Tesla MRI</arm_group_label>
    <description>A study Group of at maximum n= 80 should be collected for measuring 7 Tesla MRI at two timepoints (Baseline and 90 days) in Berlin.</description>
  </arm_group>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      -  Whole blood-/plasma (RNA-/DNA-Analysis)&#xD;
&#xD;
        -  Cerebrospinal fluid (sequencing of candidate nicotinic receptor genes and genes for&#xD;
           acetylcholine synthesis/-catabolism: CHRNA3, CHRNA4, CHRNA5, CHRNA7, CHRNB2, CHRNB4,&#xD;
           ACHE, CHAT) (only in Berlin).&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Surgical patients, 65 years or above (Berlin/Utrecht) ASA I and II patients, 65 years or&#xD;
        above (Utrecht) ASA II and III patients, 65 years or above (Berlin/Utrecht)&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Study Group (Berlin/Utrecht):&#xD;
&#xD;
        Inclusion Criteria:&#xD;
&#xD;
          -  Male and female patients aged ≥ 65 years, of European descent (Caucasian)&#xD;
&#xD;
          -  Elective surgery with an expected operative time ≥ 60 minutes&#xD;
&#xD;
          -  Ability to give informed consent after receiving spoken and written information of the&#xD;
             study&#xD;
&#xD;
          -  Eligibility for magnetic resonance Imaging&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Mini-Mental-State-Examination ≤ 23 points&#xD;
&#xD;
          -  Homelessness or other circumstances where the patient would not be reachable by phone&#xD;
             or postal services during follow-up.&#xD;
&#xD;
          -  Participation in another prospective interventional clinical study during&#xD;
             participation in this clinical study during hospital stay&#xD;
&#xD;
          -  Accommodation in an institution due to an official or judicial order&#xD;
&#xD;
          -  Missing informed consent for saving and hand out pseudonymous data&#xD;
&#xD;
          -  Neuropsychiatric morbidity, which limits the conduction of the neurocognitive testing&#xD;
&#xD;
          -  Anacusis or Hypoacusis, which limits the conduction of the neurocognitive testing&#xD;
&#xD;
        Intraoperative clectroencephalography - examinations (Study Group Berlin):&#xD;
&#xD;
        Exclusion criteria:&#xD;
&#xD;
          -  Neurological preconditions&#xD;
&#xD;
          -  Proposed neurological surgery&#xD;
&#xD;
        Control Group (Berlin/Utrecht):&#xD;
&#xD;
        Inclusion criteria:&#xD;
&#xD;
          -  Male and female patients aged ≥ 65 years, of European descent (Caucasian)&#xD;
&#xD;
          -  ASA II and III patients&#xD;
&#xD;
          -  No operation in the last half year before study inclusion&#xD;
&#xD;
          -  Eligibility for magnetic resonance Imaging&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Mini-Mental-State-Examination ≤ 23 Points&#xD;
&#xD;
          -  Missing informed consent for saving and hand out pseudonymous data&#xD;
&#xD;
          -  Neuropsychiatric morbidity, which limits the conduction of the neurocognitive testing&#xD;
&#xD;
          -  Anacusis or Hypoacusis, which limits the conduction of the neurocognitive testing&#xD;
&#xD;
          -  Taking psychothropic drugs (including sleep-inducing drug and benzodiazepine) on a&#xD;
             regular basis and substances, which limit the conduction of the neurocognitive testing&#xD;
&#xD;
        Control Group (Utrecht) - Scannervariability:&#xD;
&#xD;
        Inclusion criteria:&#xD;
&#xD;
          -  Male and female patients aged ≥ 65 years, of European descent (Caucasian)&#xD;
&#xD;
          -  ASA I and II patients&#xD;
&#xD;
          -  No operation in the last half year before study inclusion&#xD;
&#xD;
          -  Eligibility for magnetic resonance Imaging&#xD;
&#xD;
        Study Group (Berlin) - 7 Tesla MRI:&#xD;
&#xD;
        Criteria as of the 3-Tesla- study group and additionally:&#xD;
&#xD;
        Exclusion criteria:&#xD;
&#xD;
          -  absolute 7 - Tesla MRI-contraindications&#xD;
&#xD;
          -  relative 7 - Tesla MRI-contraindications&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>65 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Claudia Spies, MD Prof.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Department of Anesthesiology and Intensive Care Medicine, CVK/CCM, Charité - University Medicine Berlin</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Georg Winterer (BioCog Research Program Coordinator), MD, PhD</last_name>
    <role>Study Chair</role>
    <affiliation>Department of Anesthesiology and Intensive Care Medicine, CVK/CCM, Charité - University Medicine Berlin</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Department of Anesthesiology and Intensive Care Medicine, CCM and CVK, Charité - Universitätsmedizin Berlin</name>
      <address>
        <city>Berlin</city>
        <zip>13353</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Department of Intensive Care Medicine, University Medical Center Utrecht</name>
      <address>
        <city>Utrecht</city>
        <zip>3584 CX</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Germany</country>
    <country>Netherlands</country>
  </location_countries>
  <link>
    <url>http://www.biocog.eu</url>
    <description>Related Info</description>
  </link>
  <verification_date>September 2019</verification_date>
  <study_first_submitted>September 23, 2014</study_first_submitted>
  <study_first_submitted_qc>October 14, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 15, 2014</study_first_posted>
  <last_update_submitted>September 23, 2019</last_update_submitted>
  <last_update_submitted_qc>September 23, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">September 25, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Charite University, Berlin, Germany</investigator_affiliation>
    <investigator_full_name>Claudia Spies</investigator_full_name>
    <investigator_title>Univ.-Prof. Dr. med. C. Spies</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Emergence Delirium</mesh_term>
    <mesh_term>Cognitive Dysfunction</mesh_term>
    <mesh_term>Cognition Disorders</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02265263
org study id: BioCog
nct id: NCT02265263
lead sponsor: 
collaborator: 
has dmc: No
The research leading consortium to these results has received funding from the European Union
      Seventh Framework Programme [FP7/2007-2013] under grant agreement no 602461 (www.biocog.eu).

      The investigators will establish valid biomarkers panels (neuroimaging and molecular) for
      risk and clinical outcome prediction of postoperative delirium (POD)/postoperative cognitive
      deficit (POCD) in elective surgical patients (Age ≥ 65 years) in study centers in
      Berlin,Germany (data collection within 2 years after initial hospital stay) and Utrecht, The
      Netherlands (data collection within 1 year after initial hospital stay), thereof
      cerebrospinal fluid (only once on day of surgery in patients with planned spinal
      anesthesia/combined spinal epidural analgesia in patients, only in Berlin).

      A control group of ASA II/III- patients is collected for measuring the learning experience
      during the cognitive testings. The participants are matched on age, education, and gender to
      the study patients. The ASA II/III- control patients receive additionally MRI-scan (3 Tesla)
      at baseline, after 3 months and after 1 (Utrecht) and 2 years (Berlin).

      To analyze scanner variability we additionally measure at maximum 20 subjects (Age ≥ 65
      years, ASA I and II) from Utrecht in the MRI scanner (3-Tesla) in Berlin and vice versa.

      A study group at maximum (n= 80) and is collected for measuring 7 Tesla MRI at two timepoints
      (Baseline and 90 days).The primary endponit of this substudy is gamma amino-butyric acid
      concentration in CNS after 3-months (measured by MRI). A retrospective comparison group
      (extracting 8000 intensive care unit patient data from the patient data management system
      during the BioCog study period in 2016) to analyse economic effects that are caused by the
      implementation of quality indicators in health care.

      An interim-analysis is performed on the primary endpoint after 400 included patients.

      The resulting (multivariate) expert system is expected: 1) to support clinical
      decision-making in patient care, e.g. to balance the individual POD/POCD risk against the
      expected overall clinical outcome of an (elective) surgical intervention, 2) to allow the
      design of more sophisticated and hypothesis-driven clinical studies and drug trials
      (translational research) in the future. The latter will be possible on the basis of
      biomarker-based sub-grouping of patients and a better understanding of relevant
      pathophysiological processes.

      Furthermore, a state-of-the art clinical database and biobank will be created that does not
      yet exist worldwide. Both the expert system and the reference database/biobank will expand
      the leadership of the contributing academic institutions in this particular research area. In
      addition, the newly created biobank will become an integral part of the European Biobanking
      and Biomolecular Resources Research Infrastructure (BBMRI) which allows top address specific
      and hypothesis-driven research questions.

      Most notably, the developed (multivariate) expert system also has the potential for
      commercialization. Possible customers are: 1) physicians and hospital departments being
      involved in pre-surgical decision making, 2) pharmaceutical industry intending to conduct
      biomarker-based drug trials in POD/POCD.
observational model: Cohort
time perspective: Prospective
measure: Incidence of Delirium
time frame: Participants will be followed for the duration of hospital stay, an expected average of 7 days
description: Postoperative delirium rate, defined according to Diagnostic and Statistical Manual of Mental Disorders (DSM-V) and/or as ≥ 2 cumulative points in the nursing Delirium Screening Scale (Nu-DESC) and/or a positive Confusion Assessment Method (CAM) and/or Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) score and/or patient chart review that shows descriptions of delirium.
measure: Incidence of postoperative cognitive deficit (POCD)
time frame: Up to 3 months after the operation
description: POCD will be measured by a defined Cambridge Neuropsychological Test Automated Battery (CANTAB) POCD will be measured by a defined Cambridge Neuropsychological Test Automated Battery (CANTAB) and paper pencil tests (TMT A und B, Grooved Pegboard) and the Mini - Mental State Examination (MMSE)
measure: Duration of Delirium
time frame: Participants will be followed for the duration of hospital stay, an exspected average of 7 days
description: Diagnostic and Statistical Manual of Mental Disorders (DSM-V)
Nursing Delirium Screening Scale (Nu-DESC)
Intensive Care Delirium Screening Checklist (ICDSC)
Delirium Detection Scale (DDS)
Confusion Assessment Method for the Intensive Care Unit (CAM-ICU)
Confusion Assessment Method (CAM)
Chart Review
measure: Duration of subsyndromal postoperative delirium
time frame: Participants will be followed for the duration of hospital stay, an exspected average of 7 days
description: Nu-DESC score 1 and/or any criteria suggestive of POD (as described under "Primary Outcome Measures") that do not fulfill DSM-5 criteria for delirium.
measure: Incidence of subsyndromal postoperative delirium
time frame: Participants will be followed for the duration of hospital stay, an exspected average of 7 days
description: Nu-DESC score 1 and/or any criteria suggestive of POD (as described under "Primary Outcome Measures") that do not fulfill DSM-5 criteria for Delirium
measure: Intensive care unit length of stay
time frame: Participants will be followed for the duration of intensive care unit stay, an expected average of 5 days
measure: Hospital length of stay
time frame: Participants will be followed for the duration of hospital stay, an exspected average of 7 days
measure: Postoperative organ complications
time frame: Participants will be followed for the duration of hospital stay, an exspected average of 7 days
description: Postoperative organ complications are classified according to Clavien - Dindo classification.
measure: Incidence of postoperative cognitive deficit
time frame: 1 year, 2 years, 5 years after the operation
description: POCD will be measured by a defined Cambridge Neuropsychological Test Automated Battery (CANTAB), paper pencil tests (TMT A und B, Grooved Pegboard) and the Mini - Mental State Examination (MMSE)
measure: Socioeconomic characteristics
time frame: 3 months, 1, 2 and 5 years after the operation
description: Study center Berlin: Health economic data according to cost of patient care (The §21 dataset (diagnoses and operation-codes). Hospital costs are calculated according to the Institute for the Hospital Remuneration System (InEK) calculation scheme to compare the refinanced costs in each cost category/cost-center segment from study center Charité. Necessity and indirect costs of medical care (outpatient visits) after hospital stay.
measure: Health related quality of life
time frame: 3 months, 1, 2 and 5 years after the operation
description: Study center Berlin: Measurement by EQ-5D
measure: Barthel Index
time frame: 3 months, 1, 2 and 5 years after the operation
measure: Instrumental activities of daily living scale
time frame: 3 months, 1, 2 and 5 years after the operation
measure: Hand grip strength test
time frame: 3 months, 1, 2 and 5 years after the operation
measure: Malnutrition
time frame: 3 months, 1, 2 and 5 years after the operation
description: Mini Nutritional Assessment - Short form, Serum albumin
measure: Mobility
time frame: 3 months, 1, 2 and 5 years after the operation
description: Timed up and go test
measure: Neuroimaging Biomarker
time frame: 3 months, 1, 2 and 5 years after the operation
measure: Molecular Biomarker
time frame: 3 months
measure: Health related Quality of life
time frame: 3 months, 1 year after the operation
description: Study center Utrecht: Measurement by EQ-5D
measure: Socioeconomic characteristics
time frame: 3 months, 1 year after the operation
description: Study center Utrecht: Health economic data according to direct cost of patient care (inpatient and outpatient stays) and necessity and indirect costs of medical care (outpatient visits) after hospital stay.
measure: Heart rate variability
time frame: Study center Berlin: Participants will be followed for the duration of hospital stay, an exspected average of 7 days
measure: Light Levels (lux)
time frame: Study center Berlin: Participants will be followed for the duration of hospital stay, an exspected average of 7 days
measure: Light frequencies
time frame: Study center Berlin: Participants will be followed for the duration of hospital stay, an exspected average of 7 days
measure: Depression
time frame: Participants will be followed for the duration of hospital stay, an exspected average of 7 days
description: Hospital Anxiety and Depression Scale (HADS) (Study Center Utrecht), GDS-15 (Study Center Berlin)
measure: Anxiety
time frame: Participants will be followed for the duration of hospital stay, an exspected average of 7 days
description: Faces Anxiety Scale (FAS)
measure: Electroencephalography (EEG)- Mapping
time frame: At time of surgery
description: Study center Berlin: EEG with19 electrodes and hypo- and hyperventilation in physiological limits (no patients with neurological pre-existing conditions or proposed neuro-surgery)
measure: Mortality
time frame: 3 months, 1, 2 and 5 years after the operation
measure: Depth of consciousness index
time frame: At time of surgery
description: Depth of consciousness index measured by processive Electroencephalography and Electromyography (EEG/EMG) -Data (SedLine®)
measure: Intraoperative cerebral oxymetry
time frame: At time of surgery
measure: Changes of Electroencephalography
time frame: Participants will be followed up until the end of postanesthesia care unit, an exspected average of 2 days
description: Signals are measured by EEG Monitor and Delir Monitor software
measure: Depth of sedation
time frame: At time of surgery and Participants will be followed for the duration of intensive care unit stay, an expected average of 5 days
description: Intraoperatively: Observe´s Assessment of Alertness/Sedation scale (OAA/S) and postoperatievly: Richmond Agitation Sedation Scale (RASS)
measure: Pain Scales
time frame: 3 months
description: Perioperatively: Pain sensitivity questionnare; Pain Catastrophing Scale (PCS-GE)(PSQ); Numerische Rating Scale (NRS-V); Behavioural Pain Scale (BPS for ventilated) and BPS-NI (for non-ventilated) patients, Critical-Care Pain Observation Tool (CPOT); Rotterdam Elderly Pain Observation Scale (REPOS); Pupillometry by Neurolight; Intraoperatively: Measurement of the nociceptive flexion reflex threshold (Dolosys Paintracker); Measurement of the pupillary dilation reflex threshold (AlgiScan); Automatic collection of the data of the medication pumps; Multiple blood analysis to measure the plasma-concentrations of anesthetics; Automatic collection of the data of the SED-Line-EEG-Monitor.
measure: Quality indicators of intensive care unit
time frame: Participants will be followed for the duration of intensive care unit stay, an expected average of 5 days
description: Study Center Berlin: This endpoint aims to analyse economic effects of the prospective study patients and retrospective control subjects in the intensive care unit that are caused by the implementation of quality indicators in health care.
measure: Glucosevariability
time frame: At time of surgery and Participants will be followed for the duration of intensive care unit stay, an expected average of 5 days
description: Measured by Continuous Glucose Monitoring System
measure: Frailty
time frame: 3 months, 1, 2 and 5 years after the operation
measure: Coagulationdisorder of the blood
time frame: 3 months
description: Kidney marker
arm group label: Surgical patients - 3 Tesla MRI
description: A study group of at maximum n= 1200 is collected for measuring 3 Tesla MRI at two timepoints (Baseline and 90 days) in Berlin/Utrecht. They include surgical procedures within body cavity e.g. abdomen or thorax from departments of general surgery, urology, gynecology or thoracic surgery; orthopaedic operations (hip-, knee-, endoprosthesis or spine (including neurosurgical spine operations)); cardiac surgery and operation of extracranial/intracranial head and neck
Data collection from study center Utrecht ist within one year after initial hospital stay. Data collection from study center Berlin is within two years after initial hospital stay.
arm group label: Patients ASA II/III - 3 Tesla MRI
description: A control group of at maximum n= 300 ASA II/III- patients is collected for measuring the learning experience during the cognitive testings. They are matched on age, education, and gender to the study patients. The 104 ASA II/III- patients should receive additionally MRI-scan (3 Tesla) at baseline, after 3 months and after 1 year in Utrecht, after 3 months, after 1, 2 years in Berlin.
Data collection from study center Utrecht ist within one year after initial hospital stay. Data collection from study center Berlin is within five years after initial hospital stay.
arm group label: Volunteers ASA I/II - 3 Tesla MRI
description: To analyze scanner variability we additionally measure at maximum 20 subjects (Age ≥ 65 years) from Utrecht in the MRI scanner (3-Tesla) in Berlin and vice versa.
arm group label: Surgical patients - 7 Tesla MRI
description: A study Group of at maximum n= 80 should be collected for measuring 7 Tesla MRI at two timepoints (Baseline and 90 days) in Berlin.
-  Whole blood-/plasma (RNA-/DNA-Analysis)

        -  Cerebrospinal fluid (sequencing of candidate nicotinic receptor genes and genes for
           acetylcholine synthesis/-catabolism: CHRNA3, CHRNA4, CHRNA5, CHRNA7, CHRNB2, CHRNB4,
           ACHE, CHAT) (only in Berlin).
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 65 Years
maximum age: N/A
healthy volunteers: No
last name: Claudia Spies, MD Prof.
role: Principal Investigator
affiliation: Department of Anesthesiology and Intensive Care Medicine, CVK/CCM, Charité - University Medicine Berlin
last name: Georg Winterer (BioCog Research Program Coordinator), MD, PhD
role: Study Chair
affiliation: Department of Anesthesiology and Intensive Care Medicine, CVK/CCM, Charité - University Medicine Berlin
facility: 
facility: 
country: Germany
country: Netherlands
url: http://www.biocog.eu
description: Related Info
responsible party type: Principal Investigator
investigator affiliation: Charite University, Berlin, Germany
investigator full name: Claudia Spies
investigator title: Univ.-Prof. Dr. med. C. Spies
mesh term: Emergence Delirium
mesh term: Cognitive Dysfunction
mesh term: Cognition Disorders