Deep Brain Stimulation for Patients With Tardive Dyskinesia and or Dystonia

Tardive Dyskinesia Clinical Trial

Official title:

Deep Brain Stimulation for Patients With Tardive Dyskinesia and or Dystonia. Efficacy and Psychiatric and Cognitive Effects

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02524886
• Other study ID #: DBS for TD
• Status: Terminated
• Phase: N/A
• First received: July 27, 2015
• Last updated: May 22, 2017
• Start date: June 2015
• Est. completion date: June 25, 2017

Study information

• Verified date: May 2017
• Source: GGZ Centraal
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Rationale: Tardive dyskinesia and dystonia (TDD) are severe side effects of dopamine blocking agents, particularly antipsychotics. Deep brain stimulation (DBS) has shown to be effective in the treatment of TDD in psychiatric patients, but only reported in case reports and small clinical trials and with little attention to possible psychiatric or cognitive complications or positive effect on psychiatric symptoms.

Objective: To assess whether treatment with DBS can reduce or resolve TDD and if DBS can induce beneficial or side-effects in particular psychiatric symptoms.

Study design: A delayed onset double blind randomised controlled trial. Study population:

Adult patients with a current or previous psychiatric disorder and antipsychotic induced TDD with a stable psychiatric status during the past 6 months.

Intervention: All patients will be treated with DBS in the posteroventrolateral GPi. The groups will be randomised into immediate stimulation or delayed stimulation after 3 months.

Main study parameters/endpoints: Primary objective, improvement on the movement rating scales BFMDRS. Secondary objectives improvement on the quality of life measured on the SF-36, psychiatric stability as measured on the BPRS and the MADRS and cognitive effects as measured on the MATTIS Dementia Rating Scale, Nederlandse Leestest voor Volwassenen (NLV), 15 word test, Facial Expression of Emotion S+T (FEEST), Groninger Intelligentie Test woordopnoemen (GIT), category and letter fluency test, Trail Making Test part A and B and the Stroop colour and word test

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 1
• Est. completion date: June 25, 2017
• Est. primary completion date: May 2, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• Mental competence*

• A current or previous psychiatric illness that has been stable for at least the last six months, meaning no overt psychiatric symptoms or decompensation based on a written report of the clinician that is treating the patient

• Diagnosis of TDD, TDD symptoms developed whilst being treated with dopamine blocking agents or within three months (for oral) or within six months (for depot) after withdrawal (definition international review of neurobiology 98)(6)

• TDD must be present for at least 12 months and impede with physical and or social functioning. In this study that is defined as a score of at least 4 on the disability rating scale of the BFMDRS with at least two items scoring a minimum of two, or one item scoring a 3 or higher.

• BFMDRS >12 at the moment of evaluation

• The patient has proven treatment refractory for all other evidence based TDD treatments:

• Withdrawal of the dopamine blocking agents or a switch to clozapine and/or quetiapine for at least 3 months

• Adding tetrabenazine at the maximum tolerated dosage for at least 4 weeks

• In focal dystonia a trial with Botulinum toxin (at least three sessions)

• The patient fully understands that DBS is not a treatment for the psychiatric disorder and agrees to take his or her psychiatric medication as prescribed by their psychiatrist.

Exclusion Criteria:

• The patient has unrealistic expectations of the possible benefit of DBS or does not fully understand the possible side effects and the likelihood of their occurring.

• The patient is suicidal, a score of =4 on item 19 on the BPRS

• Mattis scale for dementia <120

• A score of =6 on the Clinical Global Impression scale (CGI) psychiatric severity scale or a BPRS =68

• A neurological disease that is the cause of the dyskinesia and/or dystonia

• Use of recreational drugs, such cocaine amphetamine or other drugs that affect TDD, within the last 3 months. Cannabis use within the last 3 months is not considered an exclusion criteria

• Previous DBS or ablative stereotactic brain surgery

• General contraindications for stereotactic surgery and general anaesthesia (e.g. severe hypertension, blood coagulation disorder)

• A seizure disorder that is not sufficiently controlled

• An implanted electronic device

• A language barrier that prevents the patients from understanding the investigators or vice versa

Related Conditions & MeSH terms

• Dyskinesias
• Dystonia
• Dystonic Disorders
• Movement Disorders
• Tardive Dyskinesia
• Tardive Dystonia

Intervention

Device:
• GPi DBS with Medtronic electorde and Activa PC pulsegenerator
The electric stimulation of 2 leads implanted in the Globus Pallidus internus

Locations

Country	Name	City	State
Netherlands	Zon en Schild	Amersfoort	Utrecht

Sponsors (3)

Lead Sponsor	Collaborator
GGZ Centraal	Maastricht University, University Medical Center Groningen

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	DBS efficacy as measured as the change on the Burke Fahn Marsden Dystonia Rating Scale (BFMDRS)	The Efficacy of the DBS as measured on the Burke Fahn Marsden Dystonia Rating Scale (BFMDRS)	Entire study, measurement at 0, 3, 6 and 12 months for immediate stimulation group and 0, 3, 6, 9, 15 months for the delayed stimulation group
Secondary	Psychiatric safety as measured on the Brief Psychiatric Rating Scale (BPRS) and the Montgomery-Åsberg Depression Rating Scale (MADRS)	Relaps of a pre-exsisting psychiatric condition or the development of a new psychiatric condition as measured on the Brief Psychiatric Rating Scale (BPRS) and the Montgomery-Åsberg Depression Rating Scale (MADRS)	Entire study, measurement at 0, 1.5, 3, 6 and 12 months for immediate stimulation group and 0, 1.5, 3, 6, 9, 15 months for the delayed stimulation group
Secondary	Cognitive side effects as measured using neuropsychological test battery	Cognitive effects of DBS as measured using neuropsychological test battery	Entire study, measurement at 0, 3 and 12 months for immediate stimulation group and 0, 3 and 15 months for the delayed stimulation group
Secondary	Quality of life as measured on the Short Form 36 (SF-36) and the World Health Organiasation Brief Quality of Life Score (WHO-Bref)	The effect of DBS stimulation on the quality of life as measured on the Short Form 36 (SF-36) and the World Health Organiasation Brief Quality of Life Score (WHO-Bref)	Entire study, measurement at 0, 3, 6 and 12 months for immediate stimulation group and 0, 3, 6, 9, 15 months for the delayed stimulation group