Comparison of the Efficacy of Double Monopolar Versus Interleaving Stimulation Modes for Pallidal Deep Brain Stimulation

Study Overview
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Brief Summary
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The aim of the study is to compare the efficacy and the safety profile of the newly introduced interleaving stimulation mode to those of the standard double monopolar stimulation mode during pallidal deep brain stimulation of primary generalized or segmental dystonia.

Detailed Description
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Background: For the treatment of drug-refractory dystonia, bilateral pallidal deep brain stimulation (GPi-DBS) is proven to be an efficient option. On average, 40-55% improvement on dystonia rating scales (DRS) could be achieved according to the results of multicenter trials lasting for years. However, a considerable portion (10-25%) of the patients experience minimal alleviation despite of good electrode placement. These patients can be regarded as non-responders to GPi-DBS defined as having either limited improvement (< 25% on DRS) or worsening. Besides adjusting the amplitude, frequency or pulse-width of stimulation, one can change the electrode configuration from the commonly applied single monopolar stimulation mode (one contact on the electrode is negative) to either double monopolar stimulation (two -usually adjacent- negative contacts on the electrode are stimulated with same amplitude and pulse-width values) or bipolar stimulation mode (one contact on the electrode is positive) in case of unsatisfactory outcomes. Although these techniques had been utilized in multicenter trials, non-responsiveness to GPi-DBS did occur. Recently the investigators have reported in the Movement Disorders that the newly introduced interleaving stimulation mode was superior to single or double monopolar stimulation in four patients who had initially (6-12 months after implantation) limited response to GPi DBS. Aims of the study: To systematically compare the efficacy and the side-effect profile of double monopolar stimulation mode to those of interleaving stimulation mode in a prospective, randomized, double-blind, and cross-over study. Methods: The investigators would enroll 20-25 patients with drug refractory segmental or generalized primary dystonia undergoing bilateral GPi-DBS implantation within a 2-3 year time frame. The inclusion and exclusion criteria would follow those of the study of Kupsch et al.

Official Title
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Comparison of the Efficacy of Double Monopolar Versus Interleaving Stimulation Modes for the Deep Brain Stimulation Treatment of Primary Generalized or Segmental Dystonia

Conditions
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Primary Dystonia

Intervention / Treatment
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* Device: Interleaving stimulation mode (Medtronic)
* Device: Double monopolar stimulation mode (Medtronic)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ages of 7 and 75 years marked disability owing to primary generalized or segmental dystonia, despite optimal pharmacologic treatment disease duration of at least 5 years. Exclusion Criteria: previous brain surgery; cognitive impairment (< 120 points on the Mattis Dementia Rating Scale) moderate-to-severe depression (> 25 points on the Beck Depression Inventory) marked brain atrophy as detected by magnetic resonance imaging other medical or psychiatric coexisting disorders that could increase the surgical risk or interfere with completion of the trial

Ages Eligible for Study
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Minimum Age: 7 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Process 1<br>Visit 1: Baseline evaluation (maximum 1 week before operation) Visit 2: Testing of electrodes and subsequent initiation of interleaving stimulation mode (4th postoperative week). Visit 3 Evaluation and cross-over to double-monopolar stimulation mode (16th postoperative week). Visit 4 Final evaluation. (28th postoperative week). | Device: Interleaving stimulation mode (Medtronic)<br>* Interleaving stimulation mode with constant frequency (125 Hz) and pulse-width (120us)parameters 'Interleavingr stimulation mode (Medtronic)'<br>* Other names: Medtronic Activa RC Interleaving Stimulation Mode;Device: Double monopolar stimulation mode (Medtronic)<br>* Double monopolar stimulation mode with constant frequency (125 Hz) and pulse-width (120us)parameters 'Double monopolar stimulation mode (Medtronic)'<br>* Other names: Medtronic Activa RC Double Monopolar Stimulation Mode;|
| Active Comparator: Process 2<br>Visit 1: Baseline evaluation (maximum 1 week before operation) Visit 2: Testing of electrodes and subsequent initiation of double-monopolar stimulation mode (4th postoperative week). Visit 3 Evaluation and cross-over to interleaving stimulation mode (16th postoperative week). Visit 4 Final evaluation. (28th postoperative week). | Device: Interleaving stimulation mode (Medtronic)<br>* Interleaving stimulation mode with constant frequency (125 Hz) and pulse-width (120us)parameters 'Interleavingr stimulation mode (Medtronic)'<br>* Other names: Medtronic Activa RC Interleaving Stimulation Mode;Device: Double monopolar stimulation mode (Medtronic)<br>* Double monopolar stimulation mode with constant frequency (125 Hz) and pulse-width (120us)parameters 'Double monopolar stimulation mode (Medtronic)'<br>* Other names: Medtronic Activa RC Double Monopolar Stimulation Mode;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Differences in severity of dystonia | Differences in severity of dystonia measured by Burke-Fahn-Marsden Dystonia Rating Scale | 7 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of treatment responders after three months deep brain stimulation | Differences in number of treatment responders (at least 25% improvement on Burke-Fahn-Marsden Dystonia Rating Scale compared to baseline) | 7 months | 
| Health-related quality of life after three months deep brain stimulation | Differences in health-related quality of life measured by EQ-5D and SF-36 scales | 7 months | 
| Side-effect profile after three months deep brain stimulation | Differences in side-effect profile measured by stuctured deep brain stimulation-related side-effect questionnaire | 7 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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dystonia, pallidal stimulation, deep brain stimulation, deep brain stimulation of GPi, GPi, interleaving stimulation