NCT02552628

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
5

participants targeted

Target at below P25 for not_applicable

Timeline
Completed

Started Jan 2016

Longer than P75 for not_applicable

Geographic Reach
1 country

3 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

September 11, 2015

Completed
6 days until next milestone

First Posted

Study publicly available on registry

September 17, 2015

Completed
4 months until next milestone

Study Start

First participant enrolled

January 1, 2016

Completed
6.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 20, 2022

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

July 20, 2022

Completed
Last Updated

August 22, 2025

Status Verified

June 1, 2023

Enrollment Period

6.6 years

First QC Date

September 11, 2015

Last Update Submit

August 20, 2025

Conditions

Severe DystoniaWilson's Disease

Keywords

Wilson's DiseaseDeep Brain Stimulationdystonia

Outcome Measures

Primary Outcomes (1)

  • Change in movement disorder evaluated by the Canadian Occupational Performance Measure (COPM) performance and satisfaction scores

    Efficacy will be assessed by the change in the COPM performance and satisfaction scores after each 4 month-period of stimulation on and off, using blinded evaluations. The COPM is a standardized outcome measure widely used in occupational therapy. This tool can facilitate the identification of functional difficulties and individualized subject-specific priorities for intervention, which may not be captured with other standardized scales.

    21 months

Secondary Outcomes (23)

  • Other movement disorder will be assessed by the reduction of the Burke-Fahn-Marsden (BFM) dystonia scale score

    21 months

  • Change in other movement disorder evaluated by the Clinical global impression (CGI) scale

    21 months

  • Change in other movement disorder evaluated by the Unified Wilson Disease Rate Scale (UWDRS)

    21 months

  • Cognitive evaluation using the Mini Mental Status Examination (MMSE)

    Screening visit (2 days)

  • Cognitive evaluation using the Frontal Assessment Battery (FAB)

    Screening visit (2 days)

  • +18 more secondary outcomes

Study Arms (2)

Stimulation "on"

EXPERIMENTAL

The deep brain stimulation is "on"

Device: Medtronic, Activa® PC "on"

Stimulation "off"

SHAM COMPARATOR

The deep brain stimulation is "off"

Device: Medtronic, Activa® PC "off"

Interventions

Medtronic, Activa® PC "on"DEVICE
Stimulation "on"
Medtronic, Activa® PC "off"DEVICE
Stimulation "off"

Eligibility Criteria

Age18 Years - 60 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64)

You may qualify if:

  • 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)

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (3)

Hospices Civils de Lyon

Lyon, France

Location

Hopital Lariboisiere

Paris, France

Location

Hôpital Fondation Adolphe de Rothschild Paris

Paris, France

Location

Related Publications (1)

  • Laurencin C, Poujois A, Bonjour M, Demily C, Klinger H, Roze E, Leclert V, Danaila T, Langlois-Jacques C, Couchonnal E, Woimant F, Obadia MA, Perez G, Pernon M, Blanchet L, Broussolle E, Vidailhet M, Kassai B, Moro E, Karachi C, Polo G, Grabli D, Portefaix A, Thobois S. Deep brain stimulation for severe dystonia associated with Wilson disease: A prospective multicenter meta-analysis of an N-of-1 trial. Eur J Neurol. 2025 Jan;32(1):e16524. doi: 10.1111/ene.16524. Epub 2024 Oct 29.

    PMID: 39468897RESULT

MeSH Terms

Conditions

DystoniaHepatolenticular Degeneration

Condition Hierarchy (Ancestors)

DyskinesiasNeurologic ManifestationsNervous System DiseasesSigns and SymptomsPathological Conditions, Signs and SymptomsLiver DiseasesDigestive System DiseasesBasal Ganglia DiseasesBrain DiseasesCentral Nervous System DiseasesBrain Diseases, Metabolic, InbornBrain Diseases, MetabolicMovement DisordersHeredodegenerative Disorders, Nervous SystemNeurodegenerative DiseasesGenetic Diseases, InbornCongenital, Hereditary, and Neonatal Diseases and AbnormalitiesMetabolism, Inborn ErrorsMetal Metabolism, Inborn ErrorsMetabolic DiseasesNutritional and Metabolic Diseases

Study Officials

  • Stéphane THOBOIS, MD

    Hospices Civils de Lyon

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
CROSSOVER
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

September 11, 2015

First Posted

September 17, 2015

Study Start

January 1, 2016

Primary Completion

July 20, 2022

Study Completion

July 20, 2022

Last Updated

August 22, 2025

Record last verified: 2023-06

Locations

FR(3)