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出境医 / 临床实验 / Predicting Cognition After DBS for Parkinson's Disease

Predicting Cognition After DBS for Parkinson's Disease

Study Description
Brief Summary:

The aim of the study is to improve estimation of cognitive outcome after STN-DBS in PD in order to

  • avoid risk factors by optimizing peri- and intraoperative management
  • personalize therapeutic strategies for optimal long-term benefit

The investigators will test possible predictors (clinical, neuropsychological, neuroimaging, electrophysiological and molecular) for the risk of cognitive dysfunction after deep brain stimulation of the subthalamic nucleus (STN-DBS) in Parkinson's disease (PD) at a single center (Charité - Universitätsmedizin Berlin, Germany). Data collection takes place prior to as well as 3 and 12 months after the STN-DBS operation. Participation is proposed to all PD patients that are planned to undergo STN-DBS after careful examination of eligibility for this treatment according to standard operation procedures.


Condition or disease
Parkinson's Disease Deep Brain Stimulation Postoperativeneurocognitive Deficit Postoperative Delirium

Detailed Description:

Additionally to clinical routine tests, we will investigate the following possible predictors of cognitive dysfunction after STN-DBS in PD:

  • Imaging biomarkers: volume of the nucleus basalis of Meynert (NBM) measured on preoperative MRI and data driven search for unknown MRI characteristics relating to the incidence of postoperative neurocognitive disorder by means of Deep Learning (Convolutional Neural Networks), test of previously established classification models
  • Molecular biomarkers in CSF: TAU, phospho-TAU, ß-Amyloid 1-40 and 1-42 as well as NFL measured preoperatively
  • Comorbidity: according to the Charlson Comorbidity Index
  • Nutritional Status: defined by the Mini Nutritional Assessment (MNA-SF)
  • Duration of intra-/perioperative brake of dopaminergic medication
  • Nature and depth of anaesthesia: general or conscious sedation and depth of consciousness: as measured by 4 channel electroencephalography (SedLine®) and during implantation of impulse generator
  • Incidence and duration of postoperative delirium: defined according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) and/or as ≥ 2 points in the nursing Delirium Screening Scale (Nu-DESC) and/or a positive Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) score, assessment three times daily during hospital stay
  • Length of stay at ICU / hospital
  • Postoperative organ complications: according to Clavien-Dindo classification
  • Localisation of bilateral electrodes and active contacts on postoperative imaging

Substudies

Correlation of domain specific CANTAB connect test scores with possible predictors and incidence of postoperative neurocognitive disorder

Social Cognition: comparison of pre- and postoperative Theory of Mind (ToM) abilities measured by the Yoni-Paradigma (assesses affective and cognitive ToM)

The resulting multivariate risk model is expected

  • to improve peri- and intraoperative management by identifying avoidable risk factors for the development of postoperative cognitive deficit
  • to support evidence-based and personalized decision-making when advising PD patients considering STN-DBS
  • to result in the development of future hypothesis-driven interventional trials on the basis of biomarker-based sub-grouping of patients
  • to allow a better understanding of underlying pathophysiological processes both PD and surgery-related regarding cognitive effects of STN-DBS
Study Design
Layout table for study information
Study Type : Observational
Estimated Enrollment : 60 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Predictors of Cognitive Change After Deep Brain Stimulation in the Subthalmic Nucleus in Parkinson's Disease
Actual Study Start Date : June 12, 2019
Estimated Primary Completion Date : June 10, 2022
Estimated Study Completion Date : August 10, 2022
Arms and Interventions
Group/Cohort
PD patients with STN-DBS
Patients with the diagnosis of Levodopa responsive idiopathic Parkinson's Disease that are planned to undergo craniectomy with implantation of bilateral DBS electrodes in the subthalamic nucleus
Controls - PD patients with medical treatment
Patients with the diagnosis of Levodopa responsive idiopathic Parkinson's Disease that do not undergo DBS for personal reasons or contraindications for this treatment. Age, sex and disease-severity matched with PD patients with STN-DBS.
Outcome Measures
Primary Outcome Measures :
  1. Change in cognitive performance after STN-DBS [ Time Frame: Difference between pre- and 12 months postoperative testing ]
    Based on cognitive screening by paper pencil test (MoCA)

  2. Incidence of postoperative neurocognitive disorder [ Time Frame: Difference between pre- and 3 and 12 months postoperative testing ]
    • According to DSM-5 criteria applying the tablet-based neuropsychological test battery Cambridge Neuropsychological Test Automated Battery (CANTAB connect)


Biospecimen Retention:   Samples Without DNA

Cholinergic biomarkers in cerebrospinal fluid (CSF)

  • TAU, phospho-TAU, ß-Amyloid 1-40 and 1-42
  • measured in CSF preoperatively

Eligibility Criteria
Layout table for eligibility information
Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

PD patients that are planned to undergo STN-DBS. Possible contraindications to DBS are tested according to clinic-intern standard operation procedures. Tests include

  • Clinical scales: DemTect, MMST, ADL, MDS-UPDRS I-IV including video documentation of MDS-UPDRS III on and off dopaminergic medication
  • Questionnaires: expectations regarding DBS, PDQ39, BDI, Starkstein-Apathie-Skala, QUIP(-RS)
  • General examinations: Routine laboratory, ECG, TTE, Chest X-Ray, lung function, 24h-RR, Duplex sonography of extracranial arteries
  • Expert opinion from related fields: Neuropsychological exam, psychiatric examination, neurosurgery and anesthisiologic consultation
Criteria

Inclusion Criteria:

  • Diagnosis of idiopathic Parkinson's Disease
  • Indication for STN-DBS

Exclusion Criteria:

  • Internistic, surgical or psychiatric contrainidications with respect to the DBS operation or treatment for the STN-DBS group
  • Dementia
  • Relevant language barrier
Contacts and Locations

Contacts
Layout table for location contacts
Contact: Dorothee Kübler, MD +4930450660528 dorothee.kuebler@charite.de

Locations
Layout table for location information
Germany
Charité - Universitätsmedizin Berlin Recruiting
Berlin, Germany, 13351
Contact: Dorothee Kübler, MD    +4930450660528    dorothee.kuebler@charite.de   
Contact: Lucia K Feldmann, MD    +4930450660298      
Sponsors and Collaborators
Charite University, Berlin, Germany
Investigators
Layout table for investigator information
Study Director: Andrea A Kühn, Prof. MD Neurology, Head of the Movement Disorders and Neuromodulation Section
Tracking Information
First Submitted Date June 9, 2019
First Posted Date June 12, 2019
Last Update Posted Date May 7, 2021
Actual Study Start Date June 12, 2019
Estimated Primary Completion Date June 10, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: June 9, 2019)
  • Change in cognitive performance after STN-DBS [ Time Frame: Difference between pre- and 12 months postoperative testing ]
    Based on cognitive screening by paper pencil test (MoCA)
  • Incidence of postoperative neurocognitive disorder [ Time Frame: Difference between pre- and 3 and 12 months postoperative testing ]
    • According to DSM-5 criteria applying the tablet-based neuropsychological test battery Cambridge Neuropsychological Test Automated Battery (CANTAB connect)
Original Primary Outcome Measures Same as current
Change History
Current Secondary Outcome Measures Not Provided
Original Secondary Outcome Measures Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title Predicting Cognition After DBS for Parkinson's Disease
Official Title Predictors of Cognitive Change After Deep Brain Stimulation in the Subthalmic Nucleus in Parkinson's Disease
Brief Summary

The aim of the study is to improve estimation of cognitive outcome after STN-DBS in PD in order to

  • avoid risk factors by optimizing peri- and intraoperative management
  • personalize therapeutic strategies for optimal long-term benefit

The investigators will test possible predictors (clinical, neuropsychological, neuroimaging, electrophysiological and molecular) for the risk of cognitive dysfunction after deep brain stimulation of the subthalamic nucleus (STN-DBS) in Parkinson's disease (PD) at a single center (Charité - Universitätsmedizin Berlin, Germany). Data collection takes place prior to as well as 3 and 12 months after the STN-DBS operation. Participation is proposed to all PD patients that are planned to undergo STN-DBS after careful examination of eligibility for this treatment according to standard operation procedures.

Detailed Description

Additionally to clinical routine tests, we will investigate the following possible predictors of cognitive dysfunction after STN-DBS in PD:

  • Imaging biomarkers: volume of the nucleus basalis of Meynert (NBM) measured on preoperative MRI and data driven search for unknown MRI characteristics relating to the incidence of postoperative neurocognitive disorder by means of Deep Learning (Convolutional Neural Networks), test of previously established classification models
  • Molecular biomarkers in CSF: TAU, phospho-TAU, ß-Amyloid 1-40 and 1-42 as well as NFL measured preoperatively
  • Comorbidity: according to the Charlson Comorbidity Index
  • Nutritional Status: defined by the Mini Nutritional Assessment (MNA-SF)
  • Duration of intra-/perioperative brake of dopaminergic medication
  • Nature and depth of anaesthesia: general or conscious sedation and depth of consciousness: as measured by 4 channel electroencephalography (SedLine®) and during implantation of impulse generator
  • Incidence and duration of postoperative delirium: defined according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) and/or as ≥ 2 points in the nursing Delirium Screening Scale (Nu-DESC) and/or a positive Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) score, assessment three times daily during hospital stay
  • Length of stay at ICU / hospital
  • Postoperative organ complications: according to Clavien-Dindo classification
  • Localisation of bilateral electrodes and active contacts on postoperative imaging

Substudies

Correlation of domain specific CANTAB connect test scores with possible predictors and incidence of postoperative neurocognitive disorder

Social Cognition: comparison of pre- and postoperative Theory of Mind (ToM) abilities measured by the Yoni-Paradigma (assesses affective and cognitive ToM)

The resulting multivariate risk model is expected

  • to improve peri- and intraoperative management by identifying avoidable risk factors for the development of postoperative cognitive deficit
  • to support evidence-based and personalized decision-making when advising PD patients considering STN-DBS
  • to result in the development of future hypothesis-driven interventional trials on the basis of biomarker-based sub-grouping of patients
  • to allow a better understanding of underlying pathophysiological processes both PD and surgery-related regarding cognitive effects of STN-DBS
Study Type Observational
Study Design Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Retention:   Samples Without DNA
Description:

Cholinergic biomarkers in cerebrospinal fluid (CSF)

  • TAU, phospho-TAU, ß-Amyloid 1-40 and 1-42
  • measured in CSF preoperatively
Sampling Method Non-Probability Sample
Study Population

PD patients that are planned to undergo STN-DBS. Possible contraindications to DBS are tested according to clinic-intern standard operation procedures. Tests include

  • Clinical scales: DemTect, MMST, ADL, MDS-UPDRS I-IV including video documentation of MDS-UPDRS III on and off dopaminergic medication
  • Questionnaires: expectations regarding DBS, PDQ39, BDI, Starkstein-Apathie-Skala, QUIP(-RS)
  • General examinations: Routine laboratory, ECG, TTE, Chest X-Ray, lung function, 24h-RR, Duplex sonography of extracranial arteries
  • Expert opinion from related fields: Neuropsychological exam, psychiatric examination, neurosurgery and anesthisiologic consultation
Condition
  • Parkinson's Disease
  • Deep Brain Stimulation
  • Postoperativeneurocognitive Deficit
  • Postoperative Delirium
Intervention Not Provided
Study Groups/Cohorts
  • PD patients with STN-DBS
    Patients with the diagnosis of Levodopa responsive idiopathic Parkinson's Disease that are planned to undergo craniectomy with implantation of bilateral DBS electrodes in the subthalamic nucleus
  • Controls - PD patients with medical treatment
    Patients with the diagnosis of Levodopa responsive idiopathic Parkinson's Disease that do not undergo DBS for personal reasons or contraindications for this treatment. Age, sex and disease-severity matched with PD patients with STN-DBS.
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Recruiting
Estimated Enrollment
 (submitted: June 9, 2019)
60
Original Estimated Enrollment Same as current
Estimated Study Completion Date August 10, 2022
Estimated Primary Completion Date June 10, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria

Inclusion Criteria:

  • Diagnosis of idiopathic Parkinson's Disease
  • Indication for STN-DBS

Exclusion Criteria:

  • Internistic, surgical or psychiatric contrainidications with respect to the DBS operation or treatment for the STN-DBS group
  • Dementia
  • Relevant language barrier
Sex/Gender
Sexes Eligible for Study: All
Ages 18 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts
Contact: Dorothee Kübler, MD +4930450660528 dorothee.kuebler@charite.de
Listed Location Countries Germany
Removed Location Countries  
 
Administrative Information
NCT Number NCT03982953
Other Study ID Numbers EA2/040/19
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement
Plan to Share IPD: Undecided
Responsible Party Dorothee Kübler, Charite University, Berlin, Germany
Study Sponsor Charite University, Berlin, Germany
Collaborators Not Provided
Investigators
Study Director: Andrea A Kühn, Prof. MD Neurology, Head of the Movement Disorders and Neuromodulation Section
PRS Account Charite University, Berlin, Germany
Verification Date May 2021