Double-blind, Multicenter Study to Assess the Efficacy of Bilateral Pallidal Stimulation in Patients With Medically Refractory Primary Cervical Dystonia

Study Overview
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Brief Summary
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The purpose of this study is to investigate the efficacy and safety of bilateral pallidal stimulation in patients with medically refractory primary cervical dystonia.

Detailed Description
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Primary cervical dystonia (CD) affects about 20-40/100.000 population. The disease is chronic and life-long. The therapy of choice are local intramuscular Botulinum Toxin injections given every three months. Oral medication such as anticholinergics or dopamine depleting drugs are usually of limited efficacy or their use is limited by intolerable side-effects. About 5-10% of CD patients develop neutralizing antibodies against Botulinum Toxin. Two previous controlled multicenter trials have shown the efficacy and safety of bilateral pallidal stimulation in patients with primary segmental and generalized dystonia (one study was performed by our group). Following surgery, patients will be randomized 1:1 to verum or placebo stimulation for a period of three months. Primary outcome measure is the TWSTRS (Toronto Western Spasmodic Torticollis Rating Scale) - a validated and widely accepted physician-based outcome measure for cervical dystonia. The independent TWSTRS raters are movement disorders specialists unaware of the stimulation status (verum/placebo) and they compare the TWSTRS-score at baseline and 3-months follow-up. Our hypothesis is that stimulated patients will have a significantly better improvement of dystonia as compared to those without stimulation (placebo group). After the 3-months period, all patients are unblinded and receive continuous effective stimulation by the implanted system. Regular follow-up visits are scheduled every 12 months for 5 years postoperatively to assess the long-term efficacy of pallidal stimulation. Side-effects are assessed in a standardized way and include the assessment of surgery-induced as well as stimulation-induced side-effects.

Official Title
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Prospective,Randomised, Double-blind, Multicenter Study to Assess the Efficacy and Safety of Bilateral Globus Pallidus Internus - in Patients With Medically Refractory Primary Cervical Dystonia

Conditions
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Cervical Dystonia

Intervention / Treatment
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* Device: Deep brain stimulation (DBS)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Primary cervical dystonia Disease duration 3 years or longer Adult patient (18 years or older) TWSTRS severity score 15 or more Non-response to Botulinum Toxin Non-response to oral antidystonic medication Informed consent Exclusion Criteria: Dementia (Mattis Dementia Rating Scale below 120) Severe depression (Beck Depression Inventory >25) Previous functional stereotactic surgery Hemidystonia or generalized dystonia Severe brain atrophy Contraindication against surgery

Ages Eligible for Study
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Minimum Age: 18 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 |
| --- | --- |
| Sham Comparator: 2<br>Sham-stimulation | Device: Deep brain stimulation (DBS)<br>* Bilateral pallidal stimulation with an implanted DBS device<br>|
| Active Comparator: 1<br>Active GPI-DBS | Device: Deep brain stimulation (DBS)<br>* Bilateral pallidal stimulation with an implanted DBS device<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Toronto Western Spasmodic Torticollis Scale (TWSTRS) at 3 months following surgery (comparison between placebo and control group) |  | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| side-effects, quality of life, depression, pain, long-term efficacy |  | 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cervical dystonia, torticollis, deep brain stimulation, pallidal stimulation, globus pallidus internus