Investigating the Use of Complex Pulse Shapes for DBS in Movement Disorders

NCT04725045 | Completed DMC

• 1 other identifier: S61020
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief 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. 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 effectiveness of complex pulse shapes to reduce side effects and improve symptom control in DBS movement patients.

Conditions

Parkinson Disease; Essential Tremor

Outcome Measures

Primary Outcomes (6)

• Stage 1: Therapeutic window = Amplitude at which therapeutic benefit is obtained versus amplitude at which side-effects occur, both expressed in mA (milliamperes).

  Amplitude at which therapeutic benefit is obtained versus amplitude at which side-effects occur, both expressed in mA (milliamperes).

  Immediately after testing

• Stage 2 ET (3 hours): tremor scores

  FTM (Fahn-Tolosa-Marin) total score. Max 116 (higher score for more tremor).

  Measured after 3 hours of stimulation

• Stage 2 ET (3 hours): ataxia scores

  ICARS (International cooperative ataxia rating scale): total score. Max 100 (higher score for more ataxia).

  Measured after 3 hours of stimulation

• Stage 2 ET (1 week): number of treatment-related adverse events as assessed by CTCAE v4.0

  Follow-up of (S)AE related to the study during that week

  During 1 week of stimulation

• Stage 2 PD (1 week): number of treatment-related adverse events as assessed by CTCAE v4.0

  Follow-up of (S)AE related to the study during that week

  During 1 week of stimulation

• Stage 3 ET (2 years): number of treatment-related adverse events as assessed by CTCAE v4.0

  Follow-up of (S)AE related to the study during those 2 years

  During 2 years of stimulation

Secondary Outcomes (22)

• Stage 1: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

  Upto one week after the study visit of stage 1

• Stage 2 ET (3 hours): Therapeutic window: Amplitude to elicit tremor arrest, amplitude to elicit ataxia, amplitude to elicit stim-induced side-effects

  Immediately after testing

• Stage 2 ET (3 hours): tremor subscores

  Measured at 1 hours, 2 hours and 3 hours after start of stimulation

• Stage 2 ET (3 hours): ataxia subscores

  Measured at 1 hours, 2 hours and 3 hours after start of stimulation

• Stage 2 ET (3 hours): speech assessment (least dysarthria)

  Measured at 1 hours, 2 hours and 3 hours after start of stimulation

Study Arms (2)

Standard clinical pulse shape

ACTIVE COMPARATOR

Standard clinical pulse shape as used in clinical practice (cathodic stimulation).

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)

Device: Boston Scientific: Study tool computer

Interventions

Boston Scientific: Study tool computer DEVICE

compare clinical outcome measurements of complex pulse shapes to standard clinical pulse shape

Complex pulse shape; Standard clinical pulse shape

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.
• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• KU Leuven: lead

Study Sites (1)

KU Leuven

Leuven, 3000, Belgium

Location

MeSH Terms

Conditions

Parkinson Disease; Essential Tremor

Condition Hierarchy (Ancestors)

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

Study Officials

• Myles Mc Laughlin, Prof. Dr.

  KU Leuven

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Masking Details: Double-blinded design
• Purpose: SUPPORTIVE CARE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Professor

Model Details: Randomized, crossover, double-blinded design

Study Record Dates

• First Submitted: November 24, 2020
• First Posted: January 26, 2021
• Study Start: February 12, 2019
• Primary Completion: April 14, 2022
• Study Completion: April 14, 2022
• Last Updated: April 29, 2022

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will not share

Locations

BE (1)