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Predicting Cognition After DBS for Parkinson's Disease

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ClinicalTrials.gov Identifier: NCT03982953
Recruitment Status : Recruiting
First Posted : June 12, 2019
Last Update Posted : June 14, 2019
Sponsor:
Information provided by (Responsible Party):
Dorothee Kübler, Charite University, Berlin, Germany

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 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

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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
Estimated Study Start Date : June 12, 2019
Estimated Primary Completion Date : December 10, 2021
Estimated Study Completion Date : December 10, 2021

Resource links provided by the National Library of Medicine


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.



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


Information from the National Library of Medicine

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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

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): NCT03982953


Contacts
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Contact: Dorothee Kübler, MD +4930450660528 dorothee.kuebler@charite.de

Locations
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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
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Study Director: Andrea A Kühn, Prof. MD Neurology, Head of the Movement Disorders and Neuromodulation Section

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Responsible Party: Dorothee Kübler, Postdoc and MD, Charite University, Berlin, Germany
ClinicalTrials.gov Identifier: NCT03982953     History of Changes
Other Study ID Numbers: EA2/040/19
First Posted: June 12, 2019    Key Record Dates
Last Update Posted: June 14, 2019
Last Verified: June 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Parkinson Disease
Delirium
Parkinsonian Disorders
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Movement Disorders
Neurodegenerative Diseases
Confusion
Neurobehavioral Manifestations
Neurologic Manifestations
Signs and Symptoms
Neurocognitive Disorders
Mental Disorders