Clinical trial NCT00148889: Double-blind, Multicenter Study to Assess the Efficacy of Bilateral Pallidal Stimulation in Patients With Medically Refractory Primary Cervical Dystonia
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Cervical Dystonia
Keywords: cervical dystonia
torticollis
deep brain stimulation
pallidal stimulation
globus pallidus internus
Lead sponsor: German Parkinson Study Group (GPS)
Sponsor class: OTHER
Collaborators: name: Medtronic
name: Competence Network on Parkinson's Disease
First posted: 2005-09-08
Enrollment: 63
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Toronto Western Spasmodic Torticollis Scale (TWSTRS) at 3 months following surgery (comparison between placebo and control group)
timeFrame: 3 months
Secondary outcomes:
measure: side-effects, quality of life, depression, pain, long-term efficacy
timeFrame: 5 years
Other outcomes:
Locations:
city: Innsbruck
country: Austria
facility: Medical University Innsbruck, Department of Neurology
state: Tyrol
city: Vienna
country: Austria
facility: Department of Neurosurgery, Medical University Vienna
city: Berlin
country: Germany
facility: Department of Neurology, Charité, Humboldt-University Berlin
city: Hannover
country: Germany
facility: Clinic of Neurosurgery, Medical University Hannover
city: Heidelberg
country: Germany
facility: Department of Neurology, University Heidelberg
city: Kiel
country: Germany
facility: Department of Neurology, University Kiel
city: Köln
country: Germany
facility: Department for Stereotaxy and Functional Neurosurgery, University Cologne
city: Regensburg
country: Germany
facility: Department of Neurology, University Regensburg
city: Rostock
country: Germany
facility: Department of Neurology, University Rostock
city: Tübingen
country: Germany
facility: Hertie-Institute for Clinical Brain Research
Study officials:
affiliation: Department of Neurology, Medical University Innsbruck, Anichstr. 35, A-6020 Innsbruck, Austria
name: Joerg Mueller, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Dinkelbach L, Mueller J, Poewe W, Delazer M, Elben S, Wolters A, Karner E, Wittstock M, Benecke R, Schnitzler A, Volkmann J, Sudmeyer M. Cognitive outcome of pallidal deep brain stimulation for primary cervical dystonia: One year follow up results of a prospective multicenter trial. Parkinsonism Relat Disord. 2015 Aug;21(8):976-80. doi: 10.1016/j.parkreldis.2015.06.002. Epub 2015 Jun 4.
citation: Volkmann J, Mueller J, Deuschl G, Kuhn AA, Krauss JK, Poewe W, Timmermann L, Falk D, Kupsch A, Kivi A, Schneider GH, Schnitzler A, Sudmeyer M, Voges J, Wolters A, Wittstock M, Muller JU, Hering S, Eisner W, Vesper J, Prokop T, Pinsker M, Schrader C, Kloss M, Kiening K, Boetzel K, Mehrkens J, Skogseid IM, Ramm-Pettersen J, Kemmler G, Bhatia KP, Vitek JL, Benecke R; DBS study group for dystonia. Pallidal neurostimulation in patients with medication-refractory cervical dystonia: a randomised, sham-controlled trial. Lancet Neurol. 2014 Sep;13(9):875-84. doi: 10.1016/S1474-4422(14)70143-7. Epub 2014 Aug 7.