Clinical trial NCT04725045: Investigating the Use of Complex Pulse Shapes for DBS in Movement Disorders
Official title: Investigating the Use of Complex Pulse Shapes for DBS in Movement Disorders
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Parkinson Disease
Essential Tremor
Lead sponsor: KU Leuven
Sponsor class: OTHER
First posted: 2021-01-26
Enrollment: 28
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Randomized, crossover, double-blinded design
Primary purpose: SUPPORTIVE_CARE

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.

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.

Eligibility 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.

Primary outcomes:
measure: Stage 1: Therapeutic window = Amplitude at which therapeutic benefit is obtained versus amplitude at which side-effects occur, both expressed in mA (milliamperes).
timeFrame: Immediately after testing
measure: Stage 2 ET (3 hours): tremor scores
timeFrame: Measured after 3 hours of stimulation
measure: Stage 2 ET (3 hours): ataxia scores
timeFrame: Measured after 3 hours of stimulation
measure: Stage 2 ET (1 week): number of treatment-related adverse events as assessed by CTCAE v4.0
timeFrame: During 1 week of stimulation
measure: Stage 2 PD (1 week): number of treatment-related adverse events as assessed by CTCAE v4.0
timeFrame: During 1 week of stimulation
measure: Stage 3 ET (2 years): number of treatment-related adverse events as assessed by CTCAE v4.0
timeFrame: During 2 years of stimulation
Secondary outcomes:
measure: Stage 1: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
timeFrame: Upto one week after the study visit of stage 1
measure: Stage 2 ET (3 hours): Therapeutic window: Amplitude to elicit tremor arrest, amplitude to elicit ataxia, amplitude to elicit stim-induced side-effects
timeFrame: Immediately after testing
measure: Stage 2 ET (3 hours): tremor subscores
timeFrame: Measured at 1 hours, 2 hours and 3 hours after start of stimulation
measure: Stage 2 ET (3 hours): ataxia subscores
timeFrame: Measured at 1 hours, 2 hours and 3 hours after start of stimulation
measure: Stage 2 ET (3 hours): speech assessment (least dysarthria)
timeFrame: Measured at 1 hours, 2 hours and 3 hours after start of stimulation
measure: Stage 2 ET (1 week): tremor scores and subscores
timeFrame: Measured after 1 week of stimulation
measure: Stage 2 ET (1 week): ataxia subscores and total score
timeFrame: Measured after 1 week of stimulation
measure: Stage 2 ET (1 week): tremor measured with Kinesia One wearable
timeFrame: Measured after 1 week of stimulation
measure: Stage 2 ET (1 week): tremor time measured with Kinesia 360
timeFrame: Measured during 1 week of stimulation
measure: Stage 2 ET (1 week): speech assessment (least dysarthria)
timeFrame: Measured after 1 week of stimulation
measure: Stage 2 ET (1 week): cognition
timeFrame: Measured after 1 week of stimulation
measure: Stage 2 ET (1 week): quality-of-life
timeFrame: Measured after 1 week of stimulation
measure: Stage 2 ET (1 week): quality-of-life
timeFrame: Measured once daily during 1 week of stimulation
measure: Stage 2 PD (1 week): therapeutic window (amplitude at loss of rigidity and amplitude at stim-induced side-effects)
timeFrame: Immediately after testing
measure: Stage 2 PD (1 week): assessment motor symptoms in Parkinson's
timeFrame: Measured after 1 week of stimulation
measure: Stage 2 PD (1 week): assessment non-motor symptoms in Parkinson's
timeFrame: Measured after 1 week of stimulation
measure: Stage 2 PD (1 week): assessment of motor symptoms in Parkinson's with Kinesia One wearable
timeFrame: Measured after 1 week of stimulation
measure: Stage 2 PD (1 week): assessment motor symptoms in Parkinson's with Kinesia 360 wearable
timeFrame: Measured after 1 week of stimulation
measure: Stage 2 PD (1 week): assessment of speech (least dysarthria)
timeFrame: Measured after 1 week of stimulation
measure: Stage 2 PD (1 week): cognition
timeFrame: Measured after 1 week of stimulation
measure: Stage 2 PD (1 week): quality-of-life
timeFrame: Measured after 1 week of stimulation
measure: Stage 2 PD (1 week): quality-of-life
timeFrame: Measured once daily during 1 week of stimulation
Other outcomes:
Locations:
city: Leuven
country: Belgium
facility: KU Leuven
Study officials:
affiliation: KU Leuven
name: Myles Mc Laughlin, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
References: