Clinical trial NCT02524886: Deep Brain Stimulation for Patients With Tardive Dyskinesia and or Dystonia
Official title: Deep Brain Stimulation for Patients With Tardive Dyskinesia and or Dystonia. Efficacy and Psychiatric and Cognitive Effects
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Tardive Dyskinesia
Tardive Dystonia
Keywords: Deep Brain Simulation
Psychiatric
Side-effects
Lead sponsor: GGZ Centraal
Sponsor class: OTHER
Collaborators: name: University Medical Center Groningen
name: Maastricht University
First posted: 2015-08-17
Enrollment: 1
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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


Eligibility criteria: 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

Primary outcomes:
measure: DBS efficacy as measured as the change on the Burke Fahn Marsden Dystonia Rating Scale (BFMDRS)
timeFrame: 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 outcomes:
measure: Psychiatric safety as measured on the Brief Psychiatric Rating Scale (BPRS) and the Montgomery-Åsberg Depression Rating Scale (MADRS)
timeFrame: 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
measure: Cognitive side effects as measured using neuropsychological test battery
timeFrame: Entire study, measurement at 0, 3 and 12 months for immediate stimulation group and 0, 3 and 15 months for the delayed stimulation group
measure: Quality of life as measured on the Short Form 36 (SF-36) and the World Health Organiasation Brief Quality of Life Score (WHO-Bref)
timeFrame: 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
Other outcomes:
Locations:
city: Amersfoort
country: Netherlands
facility: Zon en Schild
state: Utrecht
Study officials:
affiliation: GGZ Centraal
name: Peter N van Harted, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: