Deep Brain Stimulation for Patients With Tardive Dyskinesia and or Dystonia

NCT02524886 | Terminated DMC

• 1 other identifier: DBS for TD
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

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

Conditions

Tardive Dyskinesia; Tardive Dystonia

Keywords

Deep Brain Simulation; Psychiatric; Side-effects

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• Psychiatric safety 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

• Cognitive side effects 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

• 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

Study Arms (2)

Immediate stimulation

ACTIVE COMPARATOR

Patients will be implanted with a Medtronic electorde and Active PC pulse generator for deep brain stimulation at baseline and GPi electric stimulation will start immediately after surgery

Device: GPi DBS with Medtronic electorde and Activa PC pulsegenerator

Delayed stimulation

SHAM COMPARATOR

Patients will be implanted with a Medtronic electorde and Active PC pulse generator for deep brain stimulation at baseline and GPi electric stimulation will start 3 months after surgery

Device: GPi DBS with Medtronic electorde and Activa PC pulsegenerator

Interventions

GPi DBS with Medtronic electorde and Activa PC pulsegenerator DEVICE

The electric stimulation of 2 leads implanted in the Globus Pallidus internus

Also known as: DBS, GPi-DBS

Delayed stimulation; Immediate stimulation

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• GGZ Centraal: lead
• University Medical Center Groningen: collaborator
• Maastricht University: collaborator

Study Sites (1)

Zon en Schild

Amersfoort, Utrecht, 3818EW, Netherlands

Location

MeSH Terms

Conditions

Tardive Dyskinesia

Condition Hierarchy (Ancestors)

Dyskinesia, Drug-Induced; Dyskinesias; Movement Disorders; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Peter N van Harted, MD, PhD

  GGZ Centraal

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 27, 2015
• First Posted: August 17, 2015
• Study Start: June 1, 2015
• Primary Completion: May 2, 2017
• Study Completion: June 25, 2017
• Last Updated: May 23, 2017

Record last verified: 2017-05

Locations

NL (1)