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Completed

NCT Number: NCT04725045

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

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.

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Key information

Conditions

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

Age range

18 year–99 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

KU Leuven

Leuven, 3000, Belgium

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Boston Scientific: Study tool computer

Device

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

Primary outcomes

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

    Time frame: Immediately after testing

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

  2. Stage 2 ET (3 hours): tremor scores

    Time frame: Measured after 3 hours of stimulation

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

  3. Stage 2 ET (3 hours): ataxia scores

    Time frame: Measured after 3 hours of stimulation

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

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

    Time frame: During 1 week of stimulation

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

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

    Time frame: During 1 week of stimulation

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

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

    Time frame: During 2 years of stimulation

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

Secondary outcomes

  1. Stage 1: 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

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

    Time frame: Immediately after testing

    Amplitude to elicit tremor arrest, amplitude to elicit ataxia, amplitude to elicit stimulation-induced side-effects (all expressed in mA)

  3. Stage 2 ET (3 hours): tremor subscores

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

    FTM (Fahn-Tolosa-Marin) subscores: items 5, 6, 11, 12 and 13 (max 48, higher score for more tremor)

  4. Stage 2 ET (3 hours): ataxia subscores

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

    ICARS (international cooperative ataxia rating scale): item 10 (max 8, higher score for more ataxia)

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

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

    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)

  6. Stage 2 ET (1 week): tremor scores and subscores

    Time frame: Measured after 1 week of stimulation

    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)

  7. Stage 2 ET (1 week): ataxia subscores and total score

    Time frame: Measured after 1 week of stimulation

    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)

  8. Stage 2 ET (1 week): tremor measured with Kinesia One wearable

    Time frame: Measured after 1 week of stimulation

    Amount of postural tremor and kinetic tremor in both hands (max 4 per side, higher score for more tremor)

  9. Stage 2 ET (1 week): tremor time measured with Kinesia 360

    Time frame: Measured during 1 week of stimulation

    Amount of tremor time measured with Kinesia 360 wearable (%, higher score for more tremor time)

  10. Stage 2 ET (1 week): speech assessment (least dysarthria)

    Time frame: Measured after 1 week of stimulation

    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)

  11. Stage 2 ET (1 week): cognition

    Time frame: Measured after 1 week of stimulation

    MoCA (Montreal Cognitive Assessment). Max 30, higher score for better cognition.

  12. Stage 2 ET (1 week): quality-of-life

    Time frame: Measured after 1 week of stimulation

    QUEST (Quality-of-life in essential tremor questionnaire). Max 100%, higher score for worse quality-of-life.

  13. Stage 2 ET (1 week): quality-of-life

    Time frame: Measured once daily during 1 week of stimulation

    VAS (visual analogue scale) for:

    • amount of tremor
    • discomfort due to tremor Max 10, higher scores for worse outcome.

  14. Stage 2 PD (1 week): therapeutic window (amplitude at loss of rigidity and amplitude at stim-induced side-effects)

    Time frame: Immediately after testing

    Amplitude at loss of rigidity and amplitude at stimulation-induced side-effects

  15. Stage 2 PD (1 week): assessment motor symptoms in Parkinson's

    Time frame: Measured after 1 week of stimulation

    MDS-UPDRS-III (Movement Disorders Society Unified Parkinson's Disease Rating Scale, part III). Max 132, higher score for more parkinsonian symptoms.

  16. Stage 2 PD (1 week): assessment non-motor symptoms in Parkinson's

    Time frame: Measured after 1 week of stimulation

    NMSS (non-motor symptoms scale). Max 30, higher scores for more symptoms.

  17. Stage 2 PD (1 week): assessment of motor symptoms in Parkinson's with Kinesia One wearable

    Time frame: Measured after 1 week of stimulation

    Wearable scores finger tapping and hand opening. Max 4 per item, higher scores for more symptoms.

  18. Stage 2 PD (1 week): assessment motor symptoms in Parkinson's with Kinesia 360 wearable

    Time frame: Measured after 1 week of stimulation

    Wearable score amount of time that patient was bradykinetic and dyskinetic. Expressed as %, higher scores for more symptoms

  19. Stage 2 PD (1 week): assessment of speech (least dysarthria)

    Time frame: Measured after 1 week of stimulation

    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)

  20. Stage 2 PD (1 week): cognition

    Time frame: Measured after 1 week of stimulation

    MoCA (Montreal Cognitive Assessment). Max 30, higher score for better cognition.

  21. Stage 2 PD (1 week): quality-of-life

    Time frame: Measured after 1 week of stimulation

    PDQ-39 (Parkinson's disease Questionnaire): 39-item questionnaire on quality-of-life.

    Expressed in %, higher score for more symptoms.

  22. Stage 2 PD (1 week): quality-of-life

    Time frame: Measured once daily during 1 week of stimulation

    VAS (visual analogue scale) for:

    • amount of parkinsonian symptoms
    • discomfort due to parkinsonian symptoms Max 10, higher scores for worse outcome.

Sponsors and collaborators

Lead sponsor

KU Leuven

Other

Registry information

Acronym: INSHAPE_DBS

Important dates

Study start
2019
Primary completion
2022
Study completion
2022
First posted
Jan 26, 2021
Registry last updated
Apr 29, 2022

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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