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Trial record 1 of 2 for:    POD, POCD | Delirium in Old Age | Berlin, Germany
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Biomarker Development for Postoperative Cognitive Impairment in the Elderly (BioCog) (BioCog)

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ClinicalTrials.gov Identifier: NCT02265263
Recruitment Status : Recruiting
First Posted : October 15, 2014
Last Update Posted : February 22, 2019
Sponsor:
Collaborator:
European Union
Information provided by (Responsible Party):
Claudia Spies, Charite University, Berlin, Germany

Brief Summary:

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 5 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 n = 200 patients, only in Berlin). Post-mortem samples of brain tissue are analyzed in a limited number of voluntary 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, 2 and 5 years.

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

A study group (n= 80) and matched control group of (n=80, patients ASA II and III) patients 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.


Condition or disease
Postoperative Delirium (POD) Postoperative Cognitive Deficit (POCD)

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Study Type : Observational
Estimated Enrollment : 1700 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Biomarker Development for Postoperative Cognitive Impairment in the Elderly (BioCog)
Actual Study Start Date : October 2014
Actual Primary Completion Date : December 2017
Estimated Study Completion Date : September 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Delirium

Group/Cohort
Surgical patients - 3 Tesla MRI

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 five years after initial hospital stay.

Patients ASA II/III - 3 Tesla MRI

A control group of at a maximum 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 300 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 and 5 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.

Volunteers ASA I/II - 3 Tesla MRI
To analyze scanner variability we additionally measure 20 subjects (Age ≥ 65 years) from Berlin in the MRI scanner (3-Tesla) in Utrecht und vice versa 20 subjects (Age ≥ 65 years) from Utrecht in the MRI scanner (3-Tesla) in Berlin.
Surgical patients - 7 Tesla MRI
A study group (n= 80 ) is collected for measuring 7 Tesla MRI at two timepoints (Baseline and 90 days) in Berlin.
Patients ASA II/III - 7 Tesla MRI
A matched control group of (n=80, patients ASA II and III) is collected for measuring 7 Tesla MRI at two timepoints (Baseline and 90 days) in Berlin.



Primary Outcome Measures :
  1. Incidence of Delirium [ Time Frame: Participants will be followed for the duration of hospital stay, an expected average of 7 days ]
    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.

  2. Incidence of postoperative cognitive deficit (POCD) [ Time Frame: Up to 3 months after the operation ]
    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)


Secondary Outcome Measures :
  1. Duration of Delirium [ Time Frame: Participants will be followed for the duration of hospital stay, an exspected average of 7 days ]
    • 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

  2. Duration of subsyndromal postoperative delirium [ Time Frame: Participants will be followed for the duration of hospital stay, an exspected average of 7 days ]
    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.

  3. Incidence of subsyndromal postoperative delirium [ Time Frame: Participants will be followed for the duration of hospital stay, an exspected average of 7 days ]
    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

  4. 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 ]
  5. Hospital length of stay [ Time Frame: Participants will be followed for the duration of hospital stay, an exspected average of 7 days ]
  6. Postoperative organ complications [ Time Frame: Participants will be followed for the duration of hospital stay, an exspected average of 7 days ]
    Postoperative organ complications are classified according to Clavien - Dindo classification.

  7. Incidence of postoperative cognitive deficit [ Time Frame: 1 year, 2 years, 5 years after the operation ]
    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)

  8. Socioeconomic characteristics [ Time Frame: 3 months, 1, 2 and 5 years after the operation ]
    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.

  9. Health related quality of life [ Time Frame: 3 months, 1, 2 and 5 years after the operation ]
    Study center Berlin: Measurement by EQ-5D

  10. Barthel Index [ Time Frame: 3 months, 1, 2 and 5 years after the operation ]
  11. Instrumental activities of daily living scale [ Time Frame: 3 months, 1, 2 and 5 years after the operation ]
  12. Hand grip strength test [ Time Frame: 3 months, 1, 2 and 5 years after the operation ]
  13. Malnutrition [ Time Frame: 3 months, 1, 2 and 5 years after the operation ]
    Mini Nutritional Assessment - Short form, Serum albumin

  14. Mobility [ Time Frame: 3 months, 1, 2 and 5 years after the operation ]
    Timed up and go test

  15. Neuroimaging Biomarker [ Time Frame: 3 months, 1, 2 and 5 years after the operation ]
  16. Molecular Biomarker [ Time Frame: 3 months ]
  17. Health related Quality of life [ Time Frame: 3 months, 1 year after the operation ]
    Study center Utrecht: Measurement by EQ-5D

  18. Socioeconomic characteristics [ Time Frame: 3 months, 1 year after the operation ]
    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.

  19. Heart rate variability [ Time Frame: Study center Berlin: Participants will be followed for the duration of hospital stay, an exspected average of 7 days ]
  20. Light Levels (lux) [ Time Frame: Study center Berlin: Participants will be followed for the duration of hospital stay, an exspected average of 7 days ]
  21. Light frequencies [ Time Frame: Study center Berlin: Participants will be followed for the duration of hospital stay, an exspected average of 7 days ]
  22. Depression [ Time Frame: Participants will be followed for the duration of hospital stay, an exspected average of 7 days ]
    Hospital Anxiety and Depression Scale (HADS) (Study Center Utrecht), GDS-15 (Study Center Berlin)

  23. Anxiety [ Time Frame: Participants will be followed for the duration of hospital stay, an exspected average of 7 days ]
    Faces Anxiety Scale (FAS)

  24. Electroencephalography (EEG)- Mapping [ Time Frame: At time of surgery ]
    Study center Berlin: EEG with19 electrodes and hypo- and hyperventilation in physiological limits (no patients with neurological pre-existing conditions or proposed neuro-surgery)

  25. Mortality [ Time Frame: 3 months, 1, 2 and 5 years after the operation ]
  26. Depth of consciousness index [ Time Frame: At time of surgery ]
    Depth of consciousness index measured by processive Electroencephalography and Electromyography (EEG/EMG) -Data (SedLine®)

  27. Intraoperative cerebral oxymetry [ Time Frame: At time of surgery ]
  28. Changes of Electroencephalography [ Time Frame: Participants will be followed up until the end of postanesthesia care unit, an exspected average of 2 days ]
    Signals are measured by EEG Monitor and Delir Monitor software

  29. 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 ]
    Intraoperatively: Observe´s Assessment of Alertness/Sedation scale (OAA/S) and postoperatievly: Richmond Agitation Sedation Scale (RASS)

  30. Pain Scales [ Time Frame: 3 months ]
    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.

  31. 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 ]
    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.

  32. 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 ]
    Measured by Continuous Glucose Monitoring System

  33. Frailty [ Time Frame: 3 months, 1, 2 and 5 years after the operation ]
  34. Coagulationdisorder of the blood [ Time Frame: 3 months ]
    Kidney marker


Biospecimen Retention:   Samples With DNA
  • Whole blood-/plasma (RNA-/DNA-Analysis) (N = 1200)
  • Cerebrospinal fluid (sequencing of candidate nicotinic receptor genes and genes for acetylcholine synthesis/-catabolism: CHRNA3, CHRNA4, CHRNA5, CHRNA7, CHRNB2, CHRNB4, ACHE, CHAT) (N = 200, only in Berlin).


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   65 Years and older   (Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
1280 surgical patients, 65 years or above At the maximum 380 ASA (ASA Physical Status Classification System) II/III-patients, 65 years or above At the maximum 40 ASA (ASA Physical Status Classification System) I/II-patients, 65 years or above
Criteria

Study Group (Berlin/Utrecht):

Inclusion Criteria:

  • Male and female patients aged ≥ 65 years, of European descent (Caucasian)
  • Elective surgery with an expected operative time ≥ 60 minutes
  • Ability to give informed consent after receiving spoken and written information of the study
  • Eligibility for magnetic resonance Imaging

Exclusion Criteria:

  • Mini-Mental-State-Examination ≤ 23 points
  • Homelessness or other circumstances where the patient would not be reachable by phone or postal services during follow-up.
  • Participation in another prospective interventional clinical study during participation in this clinical study during hospital stay
  • Accommodation in an institution due to an official or judicial order
  • Missing informed consent for saving and hand out pseudonymous data
  • Neuropsychiatric morbidity, which limits the conduction of the neurocognitive testing
  • Anacusis or Hypoacusis, which limits the conduction of the neurocognitive testing

Intraoperative clectroencephalography - examinations (Study Group Berlin):

Exclusion criteria:

  • Neurological preconditions
  • Proposed neurological surgery

Control Group (Berlin/Utrecht):

Inclusion criteria:

  • Male and female patients aged ≥ 65 years, of European descent (Caucasian)
  • ASA II and III patients
  • No operation in the last half year before study inclusion
  • Eligibility for magnetic resonance Imaging

Exclusion Criteria:

  • Mini-Mental-State-Examination ≤ 23 Points
  • Missing informed consent for saving and hand out pseudonymous data
  • Neuropsychiatric morbidity, which limits the conduction of the neurocognitive testing
  • Anacusis or Hypoacusis, which limits the conduction of the neurocognitive testing
  • Taking psychothropic drugs (including sleep-inducing drug and benzodiazepine) on a regular basis and substances, which limit the conduction of the neurocognitive testing

Control Group (Berlin/Utrecht) - Scannervariability:

Inclusion criteria:

  • Male and female patients aged ≥ 65 years, of European descent (Caucasian)
  • ASA I and II patients
  • No operation in the last half year before study inclusion
  • Eligibility for magnetic resonance Imaging

Study Group (Berlin) and control group (Berlin) - 7 Tesla MRI:

Criteria as of the 3-Tesla- study group and 3-Tesla- control group and additionally:

Exclusion criteria:

  • absolute 7 - Tesla MRI-contraindications
  • relative 7 - Tesla MRI-contraindications

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02265263


Contacts
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Contact: Claudia Spies, MD, Prof. +49 30 450 551001 claudia.spies@charite.de
Contact: Georg Winterer, MD, PhD georg.winterer@charite.de

Locations
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Germany
Department of Anesthesiology and Intensive Care Medicine, CCM and CVK, Charité - Universitätsmedizin Berlin Recruiting
Berlin, Germany, 13353
Contact: Claudia Spies, MD, Prof.    +49 30 450 551001    claudia.spies@charite.de   
Principal Investigator: Claudia Spies, MD, Prof.         
Sub-Investigator: Anika Müller, MD         
Sub-Investigator: Fatima Yürek, MD         
Sub-Investigator: Georg Winterer, MD, PhD         
Sub-Investigator: Friedrich Borchers, MD         
Sub-Investigator: Björn Weiss, MD         
Sub-Investigator: Alida Günsberg, MD         
Sub-Investigator: Annika Wiegandt, MD         
Sub-Investigator: Alissa Wolf, MD         
Sub-Investigator: Gunnar Lachmann, MD         
Sub-Investigator: Maria Olbert, MD         
Sub-Investigator: Rudolf Mörgeli, MD         
Sub-Investigator: Daniel Hadzidiakos, MD         
Sub-Investigator: Sina Rosenblender, MD         
Netherlands
Department of Intensive Care Medicine, University Medical Center Utrecht Recruiting
Utrecht, Netherlands, 3584 CX
Contact: A.J.C. (Arjen) Slooter, MD, PhD    +31 (0) 88 75 61116    A.Slooter-3@umtrecht.nl   
Principal Investigator: A.J.C. (Arjen) Slooter, MD, PhD         
Sub-Investigator: D.S. (Judy) Veldhuijzen, PhD         
Sub-Investigator: Jeroen Hendrikse, MD, PhD         
Sub-Investigator: I.M.J. Kant, MSc         
Sub-Investigator: S.J.T. van Montfort, MSc         
Sponsors and Collaborators
Charite University, Berlin, Germany
European Union
Investigators
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Principal Investigator: Claudia Spies, MD Prof. Department of Anesthesiology and Intensive Care Medicine, CVK/CCM, Charité - University Medicine Berlin
Study Chair: Georg Winterer (BioCog Research Program Coordinator), MD, PhD Department of Anesthesiology and Intensive Care Medicine, CVK/CCM, Charité - University Medicine Berlin

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Claudia Spies, Univ.-Prof. Dr. med. C. Spies, Charite University, Berlin, Germany
ClinicalTrials.gov Identifier: NCT02265263     History of Changes
Other Study ID Numbers: BioCog
First Posted: October 15, 2014    Key Record Dates
Last Update Posted: February 22, 2019
Last Verified: February 2019

Additional relevant MeSH terms:
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Cognitive Dysfunction
Delirium
Cognition Disorders
Neurocognitive Disorders
Mental Disorders
Confusion
Neurobehavioral Manifestations
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms