Efficacy and Safety of Deep Brain Stimulation (DBS) of the Pallidal (GPi) in Patients With Tardive Dystonia

Study Overview
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Brief Summary
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The purpose of this randomized, double blind, multi-center study is to assess the efficacy and safety of bilateral pallidal deep brain stimulation in patients with tardive dystonia.

Detailed Description
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Deep brain stimulation (DBS) has been established as a new reversible, neurosurgical therapeutic option for patients suffering from disabling neurological movement disorders such as essential tremor and Parkinson´s disease. Recently, deep brain stimulation has been successfully applied in patients with primary generalized and segmental dystonia. Additionally, a number of case reports suggest that pallidal deep brain stimulation may also improve tardive dystonia, which may for instance result from the intake of neuroleptics and which is notoriously difficult to treat medically. The present study will investigate the effects of pallidal DBS using a double blind, randomized design (sham- versus verum-stimulation within a 3-months interval post implantation of the electrodes). Initially 60 patients had been calculated in a power analysis to assess significant results based on an average improvement of dystonic symptoms of 30%. However, in a recent study (Damier et al., Archives of General Psychiatry, 2007), 10 out of 10 showed a successful outcome of approximately 50% decrease on the extrapyramidal symptoms rating scale score. The exact one- sided lower 95% confidence limit would be 0.794 for this result. If such an approach is chosen for sample size estimation with 18 verum and 18 placebo patients one would obtain a power of 82% against a placebo effect of 30% success rate. For a placebo effect of 25% one needs 16+16 patients and for the placebo effect of 20% one needs 12+12 patients. We thus decided to reduce the sample size to 36- 32- 24 patients. It is expected that the continuous primary outcome measure will preserve even higher power than the binary one used in the study mentioned above. The local ethical committee has approved this.

Official Title
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Multicenter, Randomized Trial on the Effects of Pallidal Deep Brain Stimulation for Tardive Dystonia

Conditions
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Dystonia, Movement Disorder

Intervention / Treatment
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* Procedure: deep brain stimulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Operational criteria for tardive dystonia for > 18 months after cessation of neuroleptic exposure 18-75 years Relevant functional impairment in daily living activities BFMDRS > 8 or AIMS > 16 Informed written consent Exclusion Criteria: PANNS >60 (Schizophrenia) Hamilton-Score > 18 (Depression) MATTIS-Score <120 (Dementia) Preceding stereotactic neurosurgery Pronounced brain atrophy Increased bleeding risk Decreased immune status Botulinum Toxin treatment within the last 3 months

Ages Eligible for Study
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Minimum Age: 18 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: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: 1<br>device | Procedure: deep brain stimulation<br>* high frequency stimulation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improvement of the motor scale of Burke-Fahn-Marsden-Dystonia Rating Scale via blinded video assessment 3 months after starting DBS in comparison to sham-stimulated patients |  | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AIMS |  | 3 months | 
| Non-motor subscores of BMFDRS |  | 3 months | 
| Visual analogue scales for both patients and treating physicians |  | 3 months | 
| Quality of life (SF-36) |  | 3 months | 
| Psychiatric assessment (HADS-D and PANSS) |  | 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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deep brain stimulation, pallidum, tardive dystonia, randomized, double blind, multicenter