Parkinson DiseaseCHANNEL DBSNCT04658641
Characterization of Complex Pulse Shapes in Deep Brain Stimulation for Movement Disorders Using EEG and Local Field Potential Recordings
A study testing Boston Scientific: Study tool computer in people with Parkinson Disease and Essential Tremor, run by KU Leuven at 1 site in Belgium.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Parkinson Disease, Essential Tremor
- What is being tested?
- Boston Scientific: Study tool computer
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteBelgium
- Study dates
- 14 Dec 2020to 20 Jun 2023
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
- Patient is diagnosed with essential tremor by a Movement Disorder Specialist.
- Diagnosis since more than 3 years.
Show all 16Show fewer
- 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
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the 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.
- Conditions
- Parkinson Disease, Essential Tremor
- Being tested
- Boston Scientific: Study tool computer
- Medical subject headings
- Parkinson Disease, Essential Tremor
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Boston Scientific: Study tool computerDevice
Compare clinical outcome measurements of complex pulse shapes to standard clinical pulse shape
| Study group | Role | What they receive |
|---|---|---|
| Standard clinical pulse shape | Active comparator | Standard clinical pulse shape as used in clinical practice (cathodic stimulation). Receives: Device: Boston Scientific: Study tool computer |
| Complex pulse shape | Experimental | Complex pulse shape (i.e. biphasic pulse shape anode first, biphasic pulse shape cathode first, hyperpolarizing pre-pulse or depolarizing pre-pulse). Receives: Device: Boston Scientific: Study tool computer |
What is being measured
The primary outcome is the main question the study is designed to answer.
Peak height
Extracted from EEG/LFP evoked potential responses
Measured: During EEG/LFP recordings (approximately 1 hour per experiment)
Peak timing
Extracted from EEG/LFP evoked potential responses
Measured: During EEG/LFP recordings (approximately 1 hour per experiment)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Dec 2020
- Study start14 Dec 2020
- Primary completion20 Jun 2023
- Study completion20 Jun 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Parkinson DiseaseStudies of the same condition, open and under way.
- More trials run by KU LeuvenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- Randomized, crossover, blinded design
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- KU Leuven
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Myles Mc Laughlin, KU Leuven
- Investigators
- Myles Mc Laughlin, Prof. Dr., Principal investigator, KU LeuvenBart Nuttin, Prof. Dr., Principal investigator, KU Leuven
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04658641
- Sponsor's protocol ID
- S62373
- Acronym
- CHANNEL DBS
- Status last verified
- Sep 2023
- First submitted
- 24 Nov 2020
- Last updated
- 6 Sep 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Van Bogaert T, Peeters J, Boogers A, Vandenberghe W, De Vloo P, Nuttin B, Mc Laughlin M. Evoked Resonant Neural Activity Reveals an Electrophysiologic Sweet Spot for Directional Subthalamic Nucleus Deep Brain Stimulation in Parkinson's Disease. Neuromodulation. 2026 Jul;29(5):775-786. doi: 10.1016/j.neurom.2025.09.303. Epub 2025 Oct 16.
PubMed 41099685Peeters J, Boogers A, Van Bogaert T, Dembek TA, Gransier R, Wouters J, Vandenberghe W, De Vloo P, Nuttin B, Mc Laughlin M. Towards biomarker-based optimization of deep brain stimulation in Parkinson's disease patients. Front Neurosci. 2023 Jan 11;16:1091781. doi: 10.3389/fnins.2022.1091781. eCollection 2022.
PubMed 36711127Peeters J, Boogers A, Van Bogaert T, Davidoff H, Gransier R, Wouters J, Nuttin B, Mc Laughlin M. Electrophysiologic Evidence That Directional Deep Brain Stimulation Activates Distinct Neural Circuits in Patients With Parkinson Disease. Neuromodulation. 2023 Feb;26(2):403-413. doi: 10.1016/j.neurom.2021.11.002. Epub 2021 Dec 18.
PubMed 35088733
Study at a glance
From the registry record, last updated by the sponsor on 6 Sep 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Characterization of Complex Pulse Shapes in Deep Brain Stimulation for Movement Disorders Using EEG and Local Field Potential Recordings
- ClinicalTrials.gov ID
- NCT04658641
- Acronym / sponsor ID
- CHANNEL DBS / S62373
- Conditions
- Parkinson Disease, Essential Tremor
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- KU LeuvenUniversity, hospital or other
- Study start
- 14 Dec 2020 (actual)
- Primary completion
- 20 Jun 2023 (actual)
- Study completion
- 20 Jun 2023 (actual)
- First posted
- 8 Dec 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind (participant)
- Number of arms
- 2
- Model description
- Randomized, crossover, blinded design
| Arm | Type | Receives |
|---|---|---|
| Standard clinical pulse shape | Active comparator | Device: Boston Scientific: Study tool computerStandard clinical pulse shape as used in clinical practice (cathodic stimulation). |
| Complex pulse shape | Experimental | Device: Boston Scientific: Study tool computerComplex pulse shape (i.e. biphasic pulse shape anode first, biphasic pulse shape cathode first, hyperpolarizing pre-pulse or depolarizing pre-pulse). |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- 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.
- Patient is diagnosed with essential tremor by a Movement Disorder Specialist.
Key exclusion criteria (4 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Boston Scientific: Study tool computerCompare clinical outcome measurements of complex pulse shapes to standard clinical pulse shape | Device | Complex pulse shape, Standard clinical pulse shape |
Primary outcome
Peak height
Time frame: During EEG/LFP recordings (approximately 1 hour per experiment)
Extracted from EEG/LFP evoked potential responses
Peak timing
Time frame: During EEG/LFP recordings (approximately 1 hour per experiment)
Extracted from EEG/LFP evoked potential responses
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Sep 2023.
- Derived from this study: PubMed 41099685Van Bogaert T, Peeters J, Boogers A, Vandenberghe W, De Vloo P, Nuttin B, Mc Laughlin M. Evoked Resonant Neural Activity Reveals an Electrophysiologic Sweet Spot for Directional Subthalamic Nucleus Deep Brain Stimulation in Parkinson's Disease. Neuromodulation. 2026 Jul;29(5):775-786. doi: 10.1016/j.neurom.2025.09.303. Epub 2025 Oct 16.
- Derived from this study: PubMed 36711127Peeters J, Boogers A, Van Bogaert T, Dembek TA, Gransier R, Wouters J, Vandenberghe W, De Vloo P, Nuttin B, Mc Laughlin M. Towards biomarker-based optimization of deep brain stimulation in Parkinson's disease patients. Front Neurosci. 2023 Jan 11;16:1091781. doi: 10.3389/fnins.2022.1091781. eCollection 2022.
- Derived from this study: PubMed 35088733Peeters J, Boogers A, Van Bogaert T, Davidoff H, Gransier R, Wouters J, Nuttin B, Mc Laughlin M. Electrophysiologic Evidence That Directional Deep Brain Stimulation Activates Distinct Neural Circuits in Patients With Parkinson Disease. Neuromodulation. 2023 Feb;26(2):403-413. doi: 10.1016/j.neurom.2021.11.002. Epub 2021 Dec 18.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Myles Mc Laughlin, Prof. Dr. principal investigator
KU Leuven
Bart Nuttin, Prof. Dr. principal investigator
KU Leuven
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Boston Scientific: Study tool computer in people with Parkinson Disease and Essential Tremor, run by KU Leuven at 1 site in Belgium.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Peak height (time frame: During EEG/LFP recordings (approximately 1 hour per experiment)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04658641, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Sep 2023.