Clinical trial NCT00331669: Efficacy and Safety of Deep Brain Stimulation (DBS) of the Pallidal (GPi) in Patients With Tardive Dystonia
Official title: Multicenter, Randomized Trial on the Effects of Pallidal Deep Brain Stimulation for Tardive Dystonia
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Dystonia
Movement Disorder
Keywords: deep brain stimulation
pallidum
tardive dystonia
randomized
double blind
multicenter
Lead sponsor: Charite University, Berlin, Germany
Sponsor class: OTHER
Collaborators: name: Humboldt-Universität zu Berlin
name: Ruhr University of Bochum
name: Medical University of Cologne
name: Heinrich-Heine University, Duesseldorf
name: University Hospital Freiburg
name: Medical University of Hannover
name: Medical University Innsbruck
name: University of Kiel
name: Philipps University Marburg
name: Ludwig-Maximilians - University of Munich
name: University of Rostock
name: University of Regensburg
name: University Hospital Tuebingen
name: Medical University of Vienna
name: Medtronic
First posted: 2006-05-31
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: 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
timeFrame: 3 months
Secondary outcomes:
measure: AIMS
timeFrame: 3 months
measure: Non-motor subscores of BMFDRS
timeFrame: 3 months
measure: Visual analogue scales for both patients and treating physicians
timeFrame: 3 months
measure: Quality of life (SF-36)
timeFrame: 3 months
measure: Psychiatric assessment (HADS-D and PANSS)
timeFrame: 3 months
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: Andreas Kupsch
Study officials:
affiliation: Dpt. of Neurology, Augustenburger Platz 1, 13353 Berlin, Charite, Campus Virchow, Germany
name: Andreas R Kupsch, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Trottenberg T, Volkmann J, Deuschl G, Kuhn AA, Schneider GH, Muller J, Alesch F, Kupsch A. Treatment of severe tardive dystonia with pallidal deep brain stimulation. Neurology. 2005 Jan 25;64(2):344-6. doi: 10.1212/01.WNL.0000149762.80932.55.
citation: Franzini A, Marras C, Ferroli P, Zorzi G, Bugiani O, Romito L, Broggi G. Long-term high-frequency bilateral pallidal stimulation for neuroleptic-induced tardive dystonia. Report of two cases. J Neurosurg. 2005 Apr;102(4):721-5. doi: 10.3171/jns.2005.102.4.0721.
citation: Damier P, Thobois S, Witjas T, Cuny E, Derost P, Raoul S, Mertens P, Peragut JC, Lemaire JJ, Burbaud P, Nguyen JM, Llorca PM, Rascol O; French Stimulation for Tardive Dyskinesia (STARDYS) Study Group. Bilateral deep brain stimulation of the globus pallidus to treat tardive dyskinesia. Arch Gen Psychiatry. 2007 Feb;64(2):170-6. doi: 10.1001/archpsyc.64.2.170.
citation: Gruber D, Sudmeyer M, Deuschl G, Falk D, Krauss JK, Mueller J, Muller JU, Poewe W, Schneider GH, Schrader C, Vesper J, Volkmann J, Winter C, Kupsch A, Schnitzler A; DBS study group for dystonia. Neurostimulation in tardive dystonia/dyskinesia: A delayed start, sham stimulation-controlled randomized trial. Brain Stimul. 2018 Nov-Dec;11(6):1368-1377. doi: 10.1016/j.brs.2018.08.006. Epub 2018 Sep 11.