DystoniaPhase 2NCT00331669
Efficacy and Safety of Deep Brain Stimulation (DBS) of the Pallidal (GPi) in Patients With Tardive Dystonia
A Phase 2 study testing deep brain stimulation in people with Dystonia and Movement Disorder, run by Charite University, Berlin, Germany at 1 site in Germany.
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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Dystonia, Movement Disorder
- What is being tested?
- deep brain stimulation
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 24 participants
- Where
- 1 siteGermany
- Study dates
- May 2006to Dec 2010
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
Germany1 site, 1 recruiting
- Recruiting
Andreas Kupsch
Berlin, 13353
Andreas R Kupsch, MD, PhD, xx49-30-450-50 ext. 660103, andreas.kupsch@charite.de
Andrea Kuehn, MD, xx49-30-450-50 ext. 660203, andrea.kuehn@charite.de
About this study
Official title: Multicenter, Randomized Trial on the Effects of Pallidal Deep Brain Stimulation for Tardive Dystonia
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.
Read the 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.
- Conditions
- Dystonia, Movement Disorder
- Being tested
- deep brain stimulation
- Keywords
- deep brain stimulation, pallidum, tardive dystonia, randomized, double blind, multicenter
- Medical subject headings
- Dystonia, Movement Disorders, Tardive Dyskinesia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
deep brain stimulationProcedure or surgery
high frequency stimulation
| Study group | Role | What they receive |
|---|---|---|
| 1 | Placebo comparator | device Receives: Procedure: deep brain stimulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 3 months
Secondary outcomes (5)
AIMS
Measured: 3 months
Non-motor subscores of BMFDRS
Measured: 3 months
Visual analogue scales for both patients and treating physicians
Measured: 3 months
Quality of life (SF-36)
Measured: 3 months
Psychiatric assessment (HADS-D and PANSS)
Measured: 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 May 2006 (estimated)
- Study startMay 2006
- Study completionDec 2010 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for DystoniaStudies of the same condition, open and under way.
- More trials run by Charite University, Berlin, GermanyThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Outcomes assessor
- Enrolment
- 24 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Charite University, Berlin, Germany
- Sponsor type
- University, hospital or other
- Collaborators
- Humboldt-Universität zu Berlin, Ruhr University of Bochum, Medical University of Cologne, Heinrich-Heine University, Duesseldorf, University Hospital Freiburg, Medical University of Hannover, Medical University Innsbruck, University of Kiel, Philipps University Marburg, Ludwig-Maximilians - University of Munich, University of Rostock, University of Regensburg, University Hospital Tuebingen, Medical University of Vienna, Medtronic
- Investigators
- Andreas R Kupsch, MD, Principal investigator, Dpt. of Neurology, Augustenburger Platz 1, 13353 Berlin, Charite, Campus Virchow, Germany
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00331669
- Sponsor's protocol ID
- DBS and tardive dystonia
- Status last verified
- Feb 2009
- First submitted
- 26 May 2006
- Last updated
- 4 Mar 2009
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 15668437Franzini 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.
PubMed 15871516Damier 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.
PubMed 17283284Gruber 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.
PubMed 30249417
Study at a glance
From the registry record, last updated by the sponsor on 4 Mar 2009. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Multicenter, Randomized Trial on the Effects of Pallidal Deep Brain Stimulation for Tardive Dystonia
- ClinicalTrials.gov ID
- NCT00331669
- Acronym / sponsor ID
- DBS and tardive dystonia
- Conditions
- Dystonia, Movement Disorder
- Keywords
- deep brain stimulation, pallidum, tardive dystonia, randomized, double blind, multicenter
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 24 participants (estimated)
- Lead sponsor
- Charite University, Berlin, GermanyUniversity, hospital or other
- Collaborators
- Humboldt-Universität zu Berlin, Ruhr University of Bochum, Medical University of Cologne, Heinrich-Heine University, Duesseldorf, University Hospital Freiburg, Medical University of Hannover, Medical University Innsbruck, University of Kiel, Philipps University Marburg, Ludwig-Maximilians - University of Munich, University of Rostock, University of Regensburg, University Hospital Tuebingen, Medical University of Vienna, Medtronic
- Study start
- May 2006
- Study completion
- Dec 2010 (estimated)
- First posted
- 31 May 2006 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, outcomes assessor)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 1 | Placebo comparator | Procedure: deep brain stimulationdevice |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (8 listed)
- PANNS >60 (Schizophrenia)
- Hamilton-Score > 18 (Depression)
- MATTIS-Score <120 (Dementia)
- Preceding stereotactic neurosurgery
- Pronounced brain atrophy
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| deep brain stimulationhigh frequency stimulation | Procedure or surgery | 1 |
Primary outcome
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
Time frame: 3 months
5 secondary outcomes
AIMS
Time frame: 3 months
Non-motor subscores of BMFDRS
Time frame: 3 months
Visual analogue scales for both patients and treating physicians
Time frame: 3 months
Quality of life (SF-36)
Time frame: 3 months
Psychiatric assessment (HADS-D and PANSS)
Time frame: 3 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Mar 2009.
- Background: PubMed 15668437Trottenberg 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.
- Background: PubMed 15871516Franzini 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.
- Background: PubMed 17283284Damier 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.
- Derived from this study: PubMed 30249417Gruber 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.
Related trials for Dystonia
Recruiting
Impact of rTMS on Abnormal Cortical fMRI in Patients With Dystonia
Dystonia Disorder
Recruiting
Intrathecal Baclofen and Pediatric Dystonia
Dystonic Cerebral Palsy
Recruiting
Focused Ultrasound Unilateral Pallidotomy for Medication-Refractory Limb Dystonia
Limb Dystonia, Idiopathic Dystonia
Recruiting
Deep Brain Stimulation Surgery for Movement Disorders
Parkinson's Disease, Essential Tremor
Active, not recruitingPhase 1/2
Deep Brain Stimulation Surgery for Focal Hand Dystonia
Dystonia, Focal Dystonia
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Andreas R Kupsch, MD principal investigator
Dpt. of Neurology, Augustenburger Platz 1, 13353 Berlin, Charite, Campus Virchow, Germany
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing deep brain stimulation in people with Dystonia and Movement Disorder, run by Charite University, Berlin, Germany at 1 site in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 4 Mar 2009. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Andreas R Kupsch, MD, PhD (xx49-30-450-50 ext. 660103, andreas.kupsch@charite.de), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome 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 (time frame: 3 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00331669, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Mar 2009.