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

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.

Study Overview

• Status: Completed
• Conditions: Parkinson Disease; Essential Tremor
• Intervention / Treatment: Device: Boston Scientific: Study tool computer

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 in a larger number of patients of the complex pulse shape selected as most interesting from stage 1.

• ET patients will first be assessed after 3 hours of the cathodic or complex pulse (double-blind design).
• PD patients will only be assessed after 1 week of each pulse.

Stage 3 will then focus on long-term evaluation (upto 2 years). Outcomes: see stage 2.

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Belgium
  • Leuven, Belgium, 3000
    • KU Leuven

Participation Criteria

Eligibility Criteria

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

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

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Stage 1: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0	Follow-up of (S)AE related to the study upto 1 week after the experiment	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	Amplitude to elicit tremor arrest, amplitude to elicit ataxia, amplitude to elicit stimulation-induced side-effects (all expressed in mA)	Immediately after testing
Stage 2 ET (3 hours): tremor subscores	FTM (Fahn-Tolosa-Marin) subscores: items 5, 6, 11, 12 and 13 (max 48, higher score for more tremor)	Measured at 1 hours, 2 hours and 3 hours after start of stimulation
Stage 2 ET (3 hours): ataxia subscores	ICARS (international cooperative ataxia rating scale): item 10 (max 8, higher score for more ataxia)	Measured at 1 hours, 2 hours and 3 hours after start of stimulation
Stage 2 ET (3 hours): speech assessment (least dysarthria)	Tests: sustained phonation /a/, diadochokinesis /tatata/, text reading and spontaneous speech Outcome: which of both pulses has less dysarthria per test (either cathodic pulse, either experimental pulse)	Measured at 1 hours, 2 hours and 3 hours after start of stimulation
Stage 2 ET (1 week): tremor scores and subscores	FTM (Fahn-Tolosa-Marin) tremor rating scale: total score (max 116, higher score for more tremor); subscores: items 5, 6, 11, 12 and 13 (max 48, higher score for more tremor)	Measured after 1 week of stimulation
Stage 2 ET (1 week): ataxia subscores and total score	ICARS (international cooperative ataxia rating scale): total score: max 100, higher score for more ataxia; subscore: item 10 (max 8, higher score for more ataxia)	Measured after 1 week of stimulation
Stage 2 ET (1 week): tremor measured with Kinesia One wearable	Amount of postural tremor and kinetic tremor in both hands (max 4 per side, higher score for more tremor)	Measured after 1 week of stimulation
Stage 2 ET (1 week): tremor time measured with Kinesia 360	Amount of tremor time measured with Kinesia 360 wearable (%, higher score for more tremor time)	Measured during 1 week of stimulation
Stage 2 ET (1 week): speech assessment (least dysarthria)	Tests: sustained phonation /a/, diadochokinesis /tatata/, text reading and spontaneous speech Outcome: which of both pulses has less dysarthria per test (either cathodic pulse, either experimental pulse)	Measured after 1 week of stimulation
Stage 2 ET (1 week): cognition	MoCA (Montreal Cognitive Assessment). Max 30, higher score for better cognition.	Measured after 1 week of stimulation
Stage 2 ET (1 week): quality-of-life	QUEST (Quality-of-life in essential tremor questionnaire). Max 100%, higher score for worse quality-of-life.	Measured after 1 week of stimulation
Stage 2 ET (1 week): quality-of-life	VAS (visual analogue scale) for: amount of tremor; discomfort due to tremor Max 10, higher scores for worse outcome.	Measured once daily during 1 week of stimulation
Stage 2 PD (1 week): therapeutic window (amplitude at loss of rigidity and amplitude at stim-induced side-effects)	Amplitude at loss of rigidity and amplitude at stimulation-induced side-effects	Immediately after testing
Stage 2 PD (1 week): assessment motor symptoms in Parkinson's	MDS-UPDRS-III (Movement Disorders Society Unified Parkinson's Disease Rating Scale, part III). Max 132, higher score for more parkinsonian symptoms.	Measured after 1 week of stimulation
Stage 2 PD (1 week): assessment non-motor symptoms in Parkinson's	NMSS (non-motor symptoms scale). Max 30, higher scores for more symptoms.	Measured after 1 week of stimulation
Stage 2 PD (1 week): assessment of motor symptoms in Parkinson's with Kinesia One wearable	Wearable scores finger tapping and hand opening. Max 4 per item, higher scores for more symptoms.	Measured after 1 week of stimulation
Stage 2 PD (1 week): assessment motor symptoms in Parkinson's with Kinesia 360 wearable	Wearable score amount of time that patient was bradykinetic and dyskinetic. Expressed as %, higher scores for more symptoms	Measured after 1 week of stimulation
Stage 2 PD (1 week): assessment of speech (least dysarthria)	Tests: sustained phonation /a/, diadochokinesis /tatata/, text reading and spontaneous speech Outcome: which of both pulses has less dysarthria per test (either cathodic pulse, either experimental pulse)	Measured after 1 week of stimulation
Stage 2 PD (1 week): cognition	MoCA (Montreal Cognitive Assessment). Max 30, higher score for better cognition.	Measured after 1 week of stimulation
Stage 2 PD (1 week): quality-of-life	PDQ-39 (Parkinson's disease Questionnaire): 39-item questionnaire on quality-of-life. Expressed in %, higher score for more symptoms.	Measured after 1 week of stimulation
Stage 2 PD (1 week): quality-of-life	VAS (visual analogue scale) for: amount of parkinsonian symptoms; discomfort due to parkinsonian symptoms Max 10, higher scores for worse outcome.	Measured once daily during 1 week of stimulation

Collaborators and Investigators

• Sponsor: KU Leuven

Study record dates

Study Major Dates

• Study Start (Actual): February 12, 2019
• Primary Completion (Actual): April 14, 2022
• Study Completion (Actual): April 14, 2022

Study Registration Dates

• First Submitted: November 24, 2020
• First Submitted That Met QC Criteria: January 21, 2021
• First Posted (Actual): January 26, 2021

Study Record Updates

• Last Update Posted (Actual): April 29, 2022
• Last Update Submitted That Met QC Criteria: April 28, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Synucleinopathies; Neurodegenerative Diseases; Parkinson Disease; Movement Disorders; Essential Tremor
• Other Study ID Numbers: S61020

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
• product manufactured in and exported from the U.S.: No