Data-Driven Characterization of Neuronal Markers During Deep Brain Stimulation for Patients With Parkinson's Disease

NCT03079960 | Unknown

• 1 other identifier: P001449
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

Brief Summary

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) has developed into a standard therapy in the refractory stage of Parkinson's disease (PD). Implanted micro- and macroelectrodes can be used to derive neural signals from the basal ganglia (BG). Cortical signals can be obtained by measurements of the electroencephalogram (EEG) or the electrocorticogram (ECoG). Both signal types can be used to characterize the motor system of the patient and make it possible to estimate the effectiveness of a currently performed DBS. However, the relationship between such neuronal features on the one hand and the DBS stimulation parameters or the observable clinical effects on the other hand is very individual and varies from patient to patient. The aim of the present study is to: (1) determine neuronal characteristics that are informative about the clinically relevant motor status of PD patients. (2) The investigation and description of the complex non-stationary dynamics of neuronal characteristics as a consequence of changing DBS stimulation parameters. (3) The study of the effect of changing DBS stimulation parameters on motor performance. The three objectives form an important building block for future adaptive closed-loop DBS strategies (aDBS). Here, the stimulation parameters are to be adapted in the single-trial and depending on the currently detected motor state of the patient. Since this is accessible only to a very limited extent, it is to be investigated whether information about the motor state can be obtained from the neural features.

Conditions

Parkinson Disease

Keywords

Parkinson; DBS; Deep Brain Stimulation; LFP; Local Field Potentials; EEG; Electroencephalogram

Outcome Measures

Primary Outcomes (1)

• Correlation of stimulation parameters and motor performance

  For each patient, a linear regression model will be trained to predict motor performance (target variable) given a stimulation parameter set (predictor). The r-value of each of the trained models across all subjects will be compared against the r-values obtained from resampled bootstrap models. Statistical significant differences between estimated and bootstrapped models will be assessed by a Wilcoxon test with a significance level of 5%. Endpoint is prediction of motor performance as assessed by the r-values of the estimated models. Stimulation parameters will include current (mA), frequency (Hz) and impulse width (µs). Motor performance will be evaluated by various motor tests (comparable to UPDRS).

  Days 1-4 after neurosurgery

Secondary Outcomes (2)

• Correlation of motor performance and informative neural markers

  Days 1-4 after neurosurgery

• Correlation of stimulation parameters and informative neural markers

  Days 1-4 after neurosurgery

Study Arms (3)

Original patient group (PG-O)

EXPERIMENTAL

DBS implantation: patients undergo standard stereotactical neurosurgery for DBS implantation. Decision for DBS treatment has been made prior to inclusion into this study. Cables and connectors of the macro electrodes will stay externalized for four days for cDBS adjustment procedures. During externalization, patients take part in test stimulation and recording sessions during which they perform short motor tasks. The externalized connectors of the macroelectrodes allow for simultaneous stimulation of the STN and obtaining LFP recordings with electrophysiological recording and measurement devices from the STN for the fitting of DBS parameters, according to the standard clinical procedure.

Device: Electrophysiological recording and measurement devices

Chronic patient group (PG-chronic)

NO INTERVENTION

Patients in this group will take part in one recording session at any desired point in time after they have been implanted with a DBS system as part of their clinical routine treatment. During this session, which will be lasting for approx. 60 minutes, patients will execute different motor tasks while neural activity is recorded non-invasively from cortical areas via surface EEG electrodes. Recordings are performed while applying different DBS strategies. The different DBS strategies are selected as a set of safe configurations as they are used in clinical routine. The behavioral tests performed for PG-chronic are the same as conducted for PG-O.

Preoperative patient group (PG-pre)

NO INTERVENTION

Patients in this group will take part in one recording session that will take place one week prior to implantation surgery at the earliest, i.e. between day -7 and day 0. Decision for DBS treatment has been made prior to inclusion into this study. During this recording session, which will be lasting for approx. 60 minutes, patients will execute different motor tasks while neural activity is recorded non-invasively from cortical areas via surface EEG electrodes. The behavioral tests performed for PG-pre are the same as conducted for PG-O.

Interventions

Electrophysiological recording and measurement devices DEVICE

Externalization of DBS connectors and macroelectrodes for simultaneous STN stimulation LFP recordings by the use of electrophysiological recording and measurement devices.

Also known as: AlphaOmega Recording and Stimulation System, Leadpoint Recording and Stimulation System, BrainAmp Amplifier

Original patient group (PG-O)

Eligibility Criteria

• Age: 35 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female patients aged ≥ 35 and ≤ 75 years
• Patients with diagnosed PD according to UK PDS Brain Bank Criteria.
• Written informed consent.
• For PG-O and PG-pre, patients who are eligible for STN DBS Surgery according to the guidelines of the DGN (www.dgn.org)
• For PG-chronic, patients who have received permanent DBS implantation in the past and who use the DBS treatment.

You may not qualify if:

• MR Imaging shows a contraindication for microelectrode recordings. If imaging shows a high amount of blood vessels in the target region and no safe trajectory for inserting the microelectrode can be found, then the patient may receive implantation of the macroelectrode without preceding microelectrode measurements, but is excluded from the study.
• Contraindication for stereotactical neurosurgery.
• Dementia (Mattis Dementia Rating Score ≤ 130)
• Acute psychosis stated by a psychiatric physician
• Unable to give written informed consent
• Surgical contraindications
• Medications that are likely to cause interactions in the opinion of the investigator
• Fertile women not using adequate contraceptive methods: female condoms, diaphragm or coil, each used in combination with spermicides; intra-uterine device; hormonal contraception in combination with a mechanical method of contraception;
• Current or planned pregnancy, nursing period
• Contraindications according to device instructions or Investigator's Brochure:
• Diathermy (shortwave, microwave, and/or therapeutic ultrasound diathermy)
• Magnetic Resonance Imaging (MRI)
• Patient incapability
• Patients to be expected poor surgical candidates

Sponsors & Collaborators

• Prof. Dr. Volker Arnd Coenen: lead
• University of Freiburg: collaborator

Study Sites (1)

Medical Center - University of Freiburg - Clinic for Neurosurgery - Dept. of Stereotactical and Functional Neurosurgery

Freiburg im Breisgau, Baden-Wurttemberg, 79106, Germany

RECRUITING

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MeSH Terms

Conditions

Parkinson Disease

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Study Officials

• Volker Coenen, Prof. Dr.

  University Hospital Freiburg

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Volker Coenen, Prof. Dr.

CONTACT

+49 761 27050510; volker.coenen@uniklinik-freiburg.de

Michael Tangermann, Dr.

CONTACT

+49 761 2038423; michael.tangermann@blbt.uni-freiburg.de

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Prof. Dr.

Model Details: The main part of the proposed study has a duration of 2 years and will include up to 20 PD patients who are eligible to receive treatment with STN DBS. This is the interventional arm, this patient group is termed PG-O here onwards. An extension phase of the study, starting in August 2019, will consider two additional groups of patients as controls for the PG-O patient group. Firstly, patients treated chronically with DBS, who underwent DBS implantation surgery months to years ago, termed PG-chronic. Secondly, patients scheduled for DBS implantation but who have not yet been implanted, termed PG-pre. It is intended to recruit approx. n=50 patients into each control group, thus resulting in an overall study cohort size of approx. 20+50+50=120 patients.

Study Record Dates

• First Submitted: February 28, 2017
• First Posted: March 15, 2017
• Study Start: April 4, 2017
• Primary Completion: December 30, 2021
• Study Completion: December 30, 2021
• Last Updated: July 28, 2021

Record last verified: 2021-07

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)