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

• ClinicalTrials.gov Identifier: NCT04725045
• Recruitment Status: Enrolling by invitation
• First Posted: January 26, 2021
• Last Update Posted: January 26, 2021
• Sponsor: KU Leuven
• Information provided by (Responsible Party): Myles Mc Laughlin, KU Leuven

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Parkinson Disease; Essential Tremor	Device: Boston Scientific: Study tool computer	Not Applicable

Detailed Description:

The study had three stages. In the first stage, a wide range of investigatory pulse shapes in a small number of patients. The effect of the pulses on the therapeutic window will be assessed.

Stage 2 will perform a short-term chronic evaluation (30 minutes and if safe, 1 week) in a larger number of patients.

In Parkinson's disease (PD) patients (after 30 minutes):

- MDS-UPDRS-III (Movement Disorders Society - Unified Parkinson's Disease Rating Scale, part III)

In essential tremor (ET) patients (after 30 minutes):

- FTM (Fahn Tolosa Marin Tremor Rating Scale)

In PD patients (after one week):

• MDS-UPDRS-III
• PDQ-39 (Parkinson's disease questionnaire - 39 items)
• NMSS (Non-motor Symptoms Scale)

In ET patients (after one week):

• FTM
• QUEST (Questionnaire for Quality of Life in Essential Tremor)
• MOCA (Montreal Cognitive Assessment)

Stage 3 will then focus on long-term evaluation (upto 2 years). The same tests are used as after the one-week testing.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 20 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Intervention Model Description: Randomized, crossover, double-blinded design
• Masking: Double (Participant, Outcomes Assessor)
• Masking Description: Double-blinded design
• Primary Purpose: Supportive Care
• Official Title: Investigating the Use of Complex Pulse Shapes for DBS in Movement Disorders
• Actual Study Start Date: February 12, 2019
• Estimated Primary Completion Date: July 2022
• Estimated Study Completion Date: August 31, 2022

Arms and Interventions

Arm	Intervention/treatment
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

Outcome Measures

Primary Outcome Measures :

1. Therapeutic window [ Time Frame: 5 minutes ]
   Amplitude at which therapeutic benefit is obtained versus amplitude at which side-effects occur, both expressed in mA (milliamperes).
2. Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 [ Time Frame: Upto one week after the study visit of stage 1 ]
   Follow-up of (S)AE related to the study upto 1 week after the experiment

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 99 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Locations

Belgium

KU Leuven

Leuven, Belgium, 3000

Sponsors and Collaborators

KU Leuven

Investigators

• Principal Investigator: Myles Mc Laughlin, Prof. Dr.; KU Leuven

More Information

• Responsible Party: Myles Mc Laughlin, Clinical Professor, KU Leuven
• ClinicalTrials.gov Identifier: NCT04725045
• Other Study ID Numbers: S61020
• First Posted: January 26, 2021
• Last Update Posted: January 26, 2021
• Last Verified: January 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

Additional relevant MeSH terms:

Parkinson Disease; Essential Tremor; Movement Disorders; Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurodegenerative Diseases