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

Dystonia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT00331669
• Other study ID #: DBS and tardive dystonia
• Status: Recruiting
• Phase: Phase 2
• First received: May 26, 2006
• Last updated: March 3, 2009
• Start date: May 2006
• Est. completion date: December 2010

Study information

• Verified date: February 2009
• Source: Charite University, Berlin, Germany
• Contact: Andreas R Kupsch, MD, PhD
• Phone: xx49-30-450-50
• Email: andreas.kupsch[@]charite.de
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 24
• Est. completion date: December 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Dystonia
• Dystonic Disorders
• Movement Disorder
• Movement Disorders

Intervention

Procedure:
• deep brain stimulation
high frequency stimulation

Locations

Country	Name	City	State
Germany	Andreas Kupsch	Berlin

Sponsors (16)

Lead Sponsor

Collaborator

Charite University, Berlin, Germany

Heinrich-Heine University, Duesseldorf, Humboldt-Universität zu Berlin, Ludwig-Maximilians - University of Munich, Medical University Innsbruck, Medical University of Cologne, Medical University of Hannover, Medical University of Vienna, Medtronic, Philipps University Marburg Medical Center, Ruhr University of Bochum, University Hospital Freiburg, University Hospital Tuebingen, University of Kiel, University of Regensburg, University of Rostock

Country where clinical trial is conducted

Germany, 

References & Publications (3)

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. — View 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. — View Citation

Trottenberg T, Volkmann J, Deuschl G, Kühn AA, Schneider GH, Müller J, Alesch F, Kupsch A. Treatment of severe tardive dystonia with pallidal deep brain stimulation. Neurology. 2005 Jan 25;64(2):344-6. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	AIMS		3 months	No
Secondary	Non-motor subscores of BMFDRS		3 months	No
Secondary	Visual analogue scales for both patients and treating physicians		3 months	No
Secondary	Quality of life (SF-36)		3 months	No
Secondary	Psychiatric assessment (HADS-D and PANSS)		3 months	No