Skip to main content
OpenTrials
Completed

NCT Number: NCT02552628

WILSTIM - DBS (WILson STIMulation - Deep Brain Stimulation)

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.

Completed

Looking for future studies?

Notify Me

Key information

Conditions

Severe Dystonia Basal Ganglia Diseases Brain Diseases Brain Diseases, Metabolic Brain Diseases, Metabolic, Inborn Central Nervous System Diseases Congenital, Hereditary, and Neonatal Diseases and Abnormalities Digestive System Diseases Dyskinesias Dystonia Genetic Diseases, Inborn Hepatolenticular Degeneration Heredodegenerative Disorders, Nervous System Liver Diseases Metabolic Diseases Metabolism, Inborn Errors Metal Metabolism, Inborn Errors Movement Disorders Nervous System Diseases Neurodegenerative Diseases Neurologic Manifestations Nutritional and Metabolic Diseases Pathological Conditions, Signs and Symptoms Signs and Symptoms Wilson's Disease

Age range

18 year–60 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Hospices Civils de Lyon, Lyon, France

Loading trial locations.

About this study

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

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Medtronic, Activa® PC "on"

Device

Medtronic, Activa® PC "off"

Device

Primary outcomes

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

    Time frame: 21 months

    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.

Secondary outcomes

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

    Time frame: 21 months

    The reduction of the Burke-Fahn-Marsden (BFM) dystonia scale score is evaluated after each 4 month-period of stimulation on and off, using blinded video evaluations. This scale is the standard of assessments on dystonia and Parkinson.

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

    Time frame: 21 months

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

    Time frame: 21 months

    The UWDRS consists of 3 sections, including: consciousness, a historical review based on the Barthel scale, and neurological examination.

  4. Cognitive evaluation using the Mini Mental Status Examination (MMSE)

    Time frame: Screening visit (2 days)

    The MMSE is a brief 30-point questionnaire test commonly used to screen for dementia.

  5. Cognitive evaluation using the Frontal Assessment Battery (FAB)

    Time frame: Screening visit (2 days)

    The FAB is a brief tool used to assess dysexecutive symptoms.

  6. Cognitive evaluation using the BDI-II (Beck Depression Inventory)

    Time frame: Screening visit (2 days)

    The BDI-II is a self- report inventory for measuring the severity of depression.

  7. Cognitive evaluation using the similarities and matrix reasoning tests from the Wechsler Adult Intelligence Scale (WAIS-IV)

    Time frame: Pre-surgery visit (2 days)

    The test of similarities measures concrete, functional, and abstract concept formation. The test of matrix reasoning measures nonverbal analytical reasoning.

  8. Cognitive evaluation using the Modified Card Sorting Test (MCST)

    Time frame: Pre-surgery visit (2 days)

    The MCST assess problem solving and the ability to shift cognitive strategies in response to changing environmental contingencies.

  9. Cognitive evaluation using the Trail Making Test (TMT)

    Time frame: Pre-surgery visit (2 days)

    The TMT assess visuo-motor speed and task switching abilities.

  10. Cognitive evaluation using the phonemic verbal fluency task

    Time frame: Pre-surgery visit (2 days)

    The phonemic verbal fluency task assesses intrinsic response generation.

  11. Cognitive evaluation using the 16-items free and cued recall test (RL/RI 16-items)

    Time frame: Pre-surgery visit (2 days)

    The RL/RI 16-items test assesses episodic memory and especially abilities to retrieve information from memory.

  12. Change in cognitive outcome evaluated by the Tasks of the test of Attentional Performance (TAP)

    Time frame: 21 months

    The TAP is a normalized computerized battery to assess attentional and executive abilities.

  13. Change in behavioral and neuropsychiatric outcome evaluated by the "Inventaire du Syndrome Dysexécutif Comportemental" (ISDC)

    Time frame: 21 months

    The ISDC assesses behavioral dysexecutive symptoms.

  14. Change in behavioral and neuropsychiatric outcome evaluated by the Brief Psychiatric Rating Scale with anchor (BPRS-E(A))

    Time frame: 21 months

    The BPRS-E(A) is widely used to measure psychiatric symptoms and unusual behavior.

  15. Change in dysarthria and deglutition outcome evaluated by the spontaneous speech and reading

    Time frame: 21 months

  16. Change in dysarthria and deglutition outcome evaluated by the the "Batterie d'Evaluation de la Dysarthrie" (BECD)

    Time frame: 21 months

    This BECD score provides a global assessment of dysarthria severity.

  17. Change in dysarthria and deglutition outcome evaluated by the Voice Handicap Index (VHI)

    Time frame: 21 months

    The VHI is a questionnaire to quantify the functional, physical and emotional impacts of a voice disorder on a patient's quality of life.

  18. Change in dysarthria and deglutition outcome evaluated by the maximum phonation time

    Time frame: 21 months

  19. Change in dysarthria and deglutition outcome evaluated by the GRBAS (Grade, Roughness, Breathiness, Asthenia, Strain) scale

    Time frame: 21 months

    Auditory-perceptual evaluation method for hoarseness is the GRBAS scale of the Japan Society of Logopedics and Phoniatrics, which rates hoarseness.

  20. Change in dysarthria and deglutition outcome evaluated by the Deglutition Handicap Index (DHI)

    Time frame: 21 months

    The DHI questionnaire is composed of statements on deglutition related aspects in daily life. It is subdivided in three domains: physical (S) (symptoms related to swallowing), functional (F) (nutritional and respiratory consequences) and emotional (E) (psychosocial consequences).

  21. Change in dysarthria and deglutition outcome evaluated by the timed test of swallowing capacity

    Time frame: 21 months

  22. Change in social outcome evaluated by the Zarit Burden Inventory (ZBI)

    Time frame: 21 months

    The ZBI is a popular caregiver self-report measure used by many aging agencies.

  23. Tolerance of Deep Brain Stimulation: occurrence of serious adverse events

    Time frame: 23 months

    Clinical examination focusing specifically on vital signs.

Sponsors and collaborators

Lead sponsor

Hospices Civils de Lyon

Other

Registry information

Official study title

DEEP BRAIN STIMULATION FOR SEVERE DYSTONIA ASSOCIATED WITH WILSON'S DISEASE. A Prospective Multicenter Meta-analysis of Nof1 Trials

Acronym: WILSTIM DBS

Important dates

Study start
2016
Primary completion
2022
Study completion
2022
First posted
Sep 17, 2015
Registry last updated
Aug 22, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.