Characterization of Complex Pulse Shapes in Deep Brain Stimulation for Movement Disorders Using EEG and Local Field Potential Recordings (CHANNEL DBS)

September 5, 2023 updated by: Myles Mc Laughlin, KU Leuven
Parkinson's disease and essential tremor are chronic movement disorders for which there is no cure. When medication is no longer effective, deep brain stimulation (DBS) is recommended. Standard DBS is a neuromodulation method that uses a simple monophasic pulse, delivered from an electrode to stimulate neurons in a target brain area. This monophasic pulse spreads out from the electrode creating a broad, electric field that stimulates a large neural population. This can often effectively reduce motor symptoms. However, many DBS patients experience side effects - caused by stimulation of non-target neurons - and suboptimal symptom control - caused by inadequate stimulation of the correct neural target. The ability to carefully manipulate the stimulating electric field to target specific neural subpopulations could solve these problems and improve patient outcomes. The use of complex pulse shapes, specifically biphasic pulses and asymmetric pre-pulses, can control the temporal properties of the stimulation field. Evidence suggests that temporal manipulations of the stimulation field can exploit biophysical differences in neurons to target specific subpopulations. Therefore, our aim is to evaluate the direct neurophysiological effects of complex pulse shapes in DBS movement disorder patients. This will be achieved using a two-stage investigation: stage one will study the neural response to different pulse shapes using electroencephalography (EEG) recordings. Stage two will study the neural responses to different pulse shapes using intra-operative local field potential (LFP) recordings. This study only relates only to the collection of EEG and LFP recordings in DBS patients. The protocol does not cover any surgical procedures, which already take place as part of the patient's normal clinical care.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Parkinson's disease and essential tremor are chronic movement disorders for which there is no cure. When medication is no longer effective, deep brain stimulation (DBS) is recommended. Standard DBS is a neuromodulation method that uses a simple monophasic pulse, delivered from an electrode to stimulate neurons in a target brain area. This monophasic pulse spreads out from the electrode creating a broad, electric field that stimulates a large neural population. This can often effectively reduce motor symptoms. However, many DBS patients experience side effects - caused by stimulation of non-target neurons - and suboptimal symptom control - caused by inadequate stimulation of the correct neural target. The ability to carefully manipulate the stimulating electric field to target specific neural subpopulations could solve these problems and improve patient outcomes.

It has been shown that modifying the electrical waveform (e.g. pulse duration, pulse polarity, etc.) determine the spatial selectivity in functional electrical stimulation. Also, a recent clinical study examined for the first time the acute effects of anodic compared to cathodic neurostimulation in 10 PD patients. They found that thresholds for anodic stimulation were significantly higher than thresholds for cathodic stimulation, which is in agreement with previous research in animal studies and model calculations. However, they also reported a better clinical effect of anodic compared to cathodic stimulation. Furthermore, a modeling study from Anderson et al. (2018) found that fiber orientations can be selectively targeted depending on the stimulus waveform (i.e. cathodic or anodic). Another recent study examined the effect of an active symmetric biphasic pulse in 8 PD and 3 ET patients. They found that this pulse shapes produced significant clinical improvements compared to the standard clinical pulse shape.

Besides the symmetric biphasic pulse shape, the asymmetric pre-pulse shows great potential for the refinement of DBS therapy. If the pre-pulse is anodic, it has a hyperpolarizing effect and is therefore referred to as a hyperpolarizing pre-pulse. If it is cathodic, it has a depolarizing effect near the electrode and is therefore referred to as a depolarizing pre-pulse. Clinical studies focused on the use of asymmetric pulse shapes to improve the spatial selectivity by selectively exciting fibers in cochlear implant listeners13-16. Modeling studies indicate that a hyperpolarizing pre-pulse can actually decrease the threshold for axons and that the threshold is decreased more for axons close to the electrode than axons further away. This indicates that a hyperpolarizing pre-pulse may help focus the effects of stimulation to axons near the electrode, thus leading to an increase in the therapeutic window and potentially more efficient symptom control.

Evidence suggests that temporal manipulations (i.e. the use of complex pulse shapes, specifically biphasic pulses and asymmetric pre-pulses) of the stimulation field can exploit biophysical differences in neurons to target specific subpopulations. Ultimately, this may lead to an increase in the therapeutic window and/or more efficient symptom control. In this study, we aim to understand the neural mechanism underpinning the clinical effects observed by manipulating the pulse shapes, by comparing neurophysiological responses to the standard clinical pulse shapes to the responses to the complex pulse shapes. This will be achieved using two approaches. The first approach will study neural responses to different pulse shapes using electroencephalography (EEG) recordings. The second approach will study neural responses to different pulse shapes using intra-operative local field potential (LFP) recordings. This study and research protocol relates only to the collection of EEG and LFP recordings in DBS patients. The protocol does not cover any surgical procedures, which will already take place as part of the patient's normal clinical care.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
30

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Belgium
      • Leuven, Belgium, 3000
        • KU Leuven

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 99 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria for PD:

  • Diagnosis of idiopathic Parkinson's disease where the diagnosis was made by a Movement Disorder Specialist according to the MDS criteria of 2015, with a Hoehn and Yahr scale (H&Y) of at least 2 (bilateral involvement).
  • Onset of the symptoms more than five years ago.
  • MDS-UPDRS-III score of ≥30 without medication or DBS.
  • Electrodes are implanted in target area STN.

Inclusion Criteria for ET:

  • Patient is diagnosed with essential tremor by a Movement Disorder Specialist.
  • Diagnosis since more than 3 years.
  • Patient has a disabling medical-refractory upper extremity tremor without medication or DBS.
  • Patient has a postural or kinetic tremor severity score of at least 3 out of 4 in the extremity intended for treatment on the Fahn-Tolosa-Marin Clinical Rating Scale for Tremor without medication or DBS.
  • Electrodes are implanted in target area VIM.

General Inclusion Criteria:

Post-op the implanted electrodes pass an integrity check, i.e. no open or shorted electrodes.

  • Stable medications
  • Lack of dementia or depression.
  • Patient is willing and able to comply with all visits and study related procedures
  • Patient understands the study requirements and the treatment procedures and provides written informed consent before any study-specific tests or procedures are performed.
  • Patient can tolerate at least 12 hours OFF medication and per clinical judgement be able to perform all study related procedures

Exclusion Criteria:

  • Any significant psychiatric problems, including unrelated clinically significant depression.
  • Any current drug or alcohol abuse.
  • Any history of recurrent or unprovoked seizures.
  • Have any significant medical condition that is likely to interfere with study procedures or likely to confound evaluation of study endpoints, including any terminal illness with survival <12 months.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Supportive Care
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: Standard clinical pulse shape
Standard clinical pulse shape as used in clinical practice (cathodic stimulation).
Device: Boston Scientific: Study tool computer
Compare clinical outcome measurements of complex pulse shapes to standard clinical pulse shape
Experimental: Complex pulse shape
Complex pulse shape (i.e. biphasic pulse shape anode first, biphasic pulse shape cathode first, hyperpolarizing pre-pulse or depolarizing pre-pulse).
Device: Boston Scientific: Study tool computer
Compare clinical outcome measurements of complex pulse shapes to standard clinical pulse shape

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Peak height
Time Frame: During EEG/LFP recordings (approximately 1 hour per experiment)
Extracted from EEG/LFP evoked potential responses
During EEG/LFP recordings (approximately 1 hour per experiment)
Peak timing
Time Frame: During EEG/LFP recordings (approximately 1 hour per experiment)
Extracted from EEG/LFP evoked potential responses
During EEG/LFP recordings (approximately 1 hour per experiment)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
KU Leuven

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Bart Nuttin, Prof. Dr., KU Leuven
  • Principal Investigator: Myles Mc Laughlin, Prof. Dr., KU Leuven

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 14, 2020

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 20, 2023

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 20, 2023

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 24, 2020

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 1, 2020

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
December 8, 2020

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
September 6, 2023

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 5, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
September 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • S62373

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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