Clinical trial NCT02552628: WILSTIM - DBS (WILson STIMulation - Deep Brain Stimulation)
Official title: DEEP BRAIN STIMULATION FOR SEVERE DYSTONIA ASSOCIATED WITH WILSON'S DISEASE. A Prospective Multicenter Meta-analysis of Nof1 Trials
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Severe Dystonia
Wilson's Disease
Keywords: Wilson's Disease
Deep Brain Stimulation
dystonia
Lead sponsor: Hospices Civils de Lyon
Sponsor class: OTHER
First posted: 2015-09-17
Enrollment: 5
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: Dystonia in Wilson's disease represent a major issue. The persistence of disabling motor symptoms despite medical treatments justifies conducting a study on deep brain stimulation (DBS) in Wilson's disease (WD). For bradykinetic patients, subthalamic nucleus (STN) could be considered as a better target than the globus pallidus (GPi). For patients with hyperkinetic dystonia, the internal globus pallidus (GPi) will be chosen as the target of DBS.

The investigators hypothesize that STN DBS will improve Wilson's disease patients, who, despite copper chelators drugs, are still impaired by severe dystonia and akinesia (more or less associated with other movement disorders).

The investigators primary objective is to demonstrate the efficacy of STN/GPi DBS on dystonia associated with Wilson's disease.

Secondary objectives:

* To evaluate the impact of STN/GPi DBS on other movements disorders (tremor, Parkinsonism, chorea) observed in Wilson's disease.
* To describe cognitive status of patients and to evaluate the consequences of STN/GPi DBS on cognition and behavioral aspects of the disease.
* To evaluate the consequences of the stimulation on speech and swallowing.
* To evaluate the social impact of STN/GPi DBS in Wilson's disease.
* To evaluate the safety of STN/GPi DBS in the specific context of Wilson's disease.

Detailed description: 4 periods of stimulation on and off, sequence randomized at Day 0.

Eligibility criteria: Inclusion Criteria:

* Age \> 18 and \< 60 years.
* Severe neurological form of Wilson's disease with predominant dystonia and akinetic-rigid syndrome, despite optimized treatment stabilized for at least 6 months.
* Important disability due to abnormal movements (Rankin score=2 to 4).
* Absence of dementia (MMS \> 24 and BREF \> 15).
* Stable psychiatric status and absence of severe depression (BDI \<28).
* Social security coverage.
* Signature of informed consent. (signature of legal guardian for subjects under protection)

Exclusion Criteria:

* Severe hepatopathy with coagulation disorders (Platelet count \< 100 G / l; INR \> 1.5; V factor deficit; low level of fibrinogen \< 1g/dL; increased of fibrin degradation products; low level of antithrombin).
* Liver transplanted patients \< 2 years
* Patients under immunosupressive drugs and corticoids regimen.
* Participation to another biomedical research involving any drugs.
* Severe and uncontrolled psychosis or depression.
* Major atrophy on brain MRI that could represent a problem for leads implantation.
* Necrosis of the STN/GPi on brain MRI.
* Female subjects who are pregnant or lactating.

Primary outcomes:
measure: Change in movement disorder evaluated by the Canadian Occupational Performance Measure (COPM) performance and satisfaction scores
timeFrame: 21 months
Secondary outcomes:
measure: Other movement disorder will be assessed by the reduction of the Burke-Fahn-Marsden (BFM) dystonia scale score
timeFrame: 21 months
measure: Change in other movement disorder evaluated by the Clinical global impression (CGI) scale
timeFrame: 21 months
measure: Change in other movement disorder evaluated by the Unified Wilson Disease Rate Scale (UWDRS)
timeFrame: 21 months
measure: Cognitive evaluation using the Mini Mental Status Examination (MMSE)
timeFrame: Screening visit (2 days)
measure: Cognitive evaluation using the Frontal Assessment Battery (FAB)
timeFrame: Screening visit (2 days)
measure: Cognitive evaluation using the BDI-II (Beck Depression Inventory)
timeFrame: Screening visit (2 days)
measure: Cognitive evaluation using the similarities and matrix reasoning tests from the Wechsler Adult Intelligence Scale (WAIS-IV)
timeFrame: Pre-surgery visit (2 days)
measure: Cognitive evaluation using the Modified Card Sorting Test (MCST)
timeFrame: Pre-surgery visit (2 days)
measure: Cognitive evaluation using the Trail Making Test (TMT)
timeFrame: Pre-surgery visit (2 days)
measure: Cognitive evaluation using the phonemic verbal fluency task
timeFrame: Pre-surgery visit (2 days)
measure: Cognitive evaluation using the 16-items free and cued recall test (RL/RI 16-items)
timeFrame: Pre-surgery visit (2 days)
measure: Change in cognitive outcome evaluated by the Tasks of the test of Attentional Performance (TAP)
timeFrame: 21 months
measure: Change in behavioral and neuropsychiatric outcome evaluated by the "Inventaire du Syndrome Dysexécutif Comportemental" (ISDC)
timeFrame: 21 months
measure: Change in behavioral and neuropsychiatric outcome evaluated by the Brief Psychiatric Rating Scale with anchor (BPRS-E(A))
timeFrame: 21 months
measure: Change in dysarthria and deglutition outcome evaluated by the spontaneous speech and reading
timeFrame: 21 months
measure: Change in dysarthria and deglutition outcome evaluated by the the "Batterie d'Evaluation de la Dysarthrie" (BECD)
timeFrame: 21 months
measure: Change in dysarthria and deglutition outcome evaluated by the Voice Handicap Index (VHI)
timeFrame: 21 months
measure: Change in dysarthria and deglutition outcome evaluated by the maximum phonation time
timeFrame: 21 months
measure: Change in dysarthria and deglutition outcome evaluated by the GRBAS (Grade, Roughness, Breathiness, Asthenia, Strain) scale
timeFrame: 21 months
measure: Change in dysarthria and deglutition outcome evaluated by the Deglutition Handicap Index (DHI)
timeFrame: 21 months
measure: Change in dysarthria and deglutition outcome evaluated by the timed test of swallowing capacity
timeFrame: 21 months
measure: Change in social outcome evaluated by the Zarit Burden Inventory (ZBI)
timeFrame: 21 months
measure: Tolerance of Deep Brain Stimulation: occurrence of serious adverse events
timeFrame: 23 months
Other outcomes:
Locations:
city: Lyon
country: France
facility: Hospices Civils de Lyon
city: Paris
country: France
facility: Hopital Lariboisiere
city: Paris
country: France
facility: Hôpital Fondation Adolphe de Rothschild Paris
Study officials:
affiliation: Hospices Civils de Lyon
name: Stéphane THOBOIS, MD
role: PRINCIPAL_INVESTIGATOR
References: