Efficacy and Safety of DBS in Patients With Primary Dystonia

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety and effectiveness of deep brain stimulation (DBS) of the subthalamic nucleus (STN) and globus pallidus internus (GPi) for primary dystonia.

Detailed Description
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Dystonia is an uncommon brain disorder in which there is abnormal muscle tone producing twisting, writhing movements and abnormal postures. It is associated with abnormal electrical activity in two groups of nerve cells in the brain called the globus pallidus internus (GPi) and the subthalamic nucleus (STN). GPi DBS appears to be effective for medication-refractory focal and segmental dystonia affecting the cranial and cervical regions in open-label series, but recently GPi stimulation has been associated with subtle motor disturbances in previously non-dystonic body regions (i.e., arms and legs) in this population of patients. DBS of the STN has also been reported to be effective for treating generalized and cervical dystonia in small open label trials. STN DBS for cranial and cervical regions may provide similar efficacy in the treatment of dystonia as GPi DBS, but without unwanted stimulation-induced motor effects. Objectives of this study is to evaluate the safety and efficacy of STN-DBS and GPi-DBS for dystonia; Participants will be evaluated pre- and postoperatively with standard dystonia rating scales including the Burke-Fahn-Marsden Dystonia rating scale (BFMDRS), Changes in cognitive function will be assessed with neuropsychological testing. Stimulation parameters will be documented, and a patient questionnaire will be administered postoperatively to determine if patients are experiencing stimulation-induced motor adverse effects. Patient weight will be recorded at study visits. This pilot study will provide preliminary open label efficacy outcomes for STN DBS in the treatment of primary dystonia and will help determine if this target should be compared to GPi DBS in a larger double-blind trial.

Official Title
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Subthalamic Nucleus (STN) and Globus Pallidus Internus (GPi) Deep Brain Stimulation (DBS) in Patients With Primary Dystonia（RELAX Study）

Conditions
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Dystonia

Intervention / Treatment
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* Device: Beijing Pins Medical Co., Ltd. Deep Brain Stimulator


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Refractory primary (systemic, segmental) dystonia diagnosed by a movement disorders neurologist Severe functional impairment despite optimal medical management, including failed botulinum toxin therapy Ability to follow up with post-operative study visits Patients and their relatives have reasonable surgery expectations Volunteer to participate in clinical trials, and signed consent form Age 6-60 years Exclusion Criteria: Pregnancy or plan a pregnancy Good treatment with Non-invasive therapy Dopamine reactive dystonia ，Genetic degeneration ，Paroxysmal dystonia ，Secondary dystonia， Psychogenic dystonia Brain MRI showing extensive brain atrophy or small vessel ischemic disease Cognitive impairment(MMSE<24) Severe depression or other serious mental illness History of traumatic brain injury, tumor, or severe cerebrovascular disease Severe brain atrophy (diagnosed by CT or MRI) Hyperthermia therapy in implant parts Abnormal in blood inspection, blood clotting disorders, liver and kidney dysfunction, or other clinical judgment cannot tolerate surgery High blood pressure, serious heart diseases, or respiratory diseases Diabetes Long-term treatment of immunosuppressive or hormones Implant pacemakers, defibrillators, cochlear and other nerve stimulators Other diseases need frequent MRI examinations Participated in any other clinical trials within 3 months Reluctant or unable to implant surgery Reluctant or unable to cooperate with follow-up Other exclusion Criteria by researchers

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 60 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: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: STN<br>DBS target with Subthalamic Nucleus (STN). | Device: Beijing Pins Medical Co., Ltd. Deep Brain Stimulator<br>* Deep Brain Stimulation for primary dystonia subjects<br>|
| Experimental: GPi<br>DBS target with Globus Pallidus Internus (GPi). | Device: Beijing Pins Medical Co., Ltd. Deep Brain Stimulator<br>* Deep Brain Stimulation for primary dystonia subjects<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| change in Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) movement score |  | 3，6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Short-Form General Health Survey (SF-36) | Quality of life was assessed with the Medical Outcomes Study 36-item Short-Form General Health Survey (SF-36), which evaluates both physical and mental components of functioning on a scale of 0 to 100, with higher scores indicating a higher level of function. | 3，6 monthsthe Beck Anxiety Inventory31 (with scores ranging from 0 to 63 and higher scores indicating more severe anxiety) | 
| Visual analogue scale | The severity of dystonia and pain was assessed with the use of a visual analogue scale, with scores ranging from 0 to 10 and higher scores indicating greater severity | 3，6 months | 
| Measurements of walking | Measurements of walking (the duration and number of steps taken in a 14-m walk with one turn) | 3，6 months | 
| The Beck Depression Inventory | The Beck Depression Inventory (with scores ranging from 0 to 63 and higher scores indicating more severe depression) | 3，6 months | 
| Mini-Mental State Examination | Cognitive were assessed by mini-mental state examination | 3，6 months | 
| The rate of improvement of BFMDRS score | The rate of improvement of BFMDRS score that >25%、>50%、>75% | 3，6 months |