Clinical Trial: WILSTIM - DBS (WILson STIMulation - Deep Brain Stimulation)

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

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

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 Summary: 4 periods of stimulation on and off, sequence randomized at Day 0.
Sponsor: Hospices Civils de Lyon

Current Primary Outcome: 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.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • 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.
  • Change in other movement disorder evaluated by the Clinical global impression (CGI) scale [ Time Frame: 21 months ]
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • Cognitive evaluation using the phonemic verbal fluency task [ Time Frame: Pre-surgery visit (2 days) ]
    The phonemic verbal fluency task assesses intrinsic response generation.
  • 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.
  • 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.
  • 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.
  • 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.
  • Change in dysarthria and deglutition outcome evaluated by the spontaneous speech and reading [ Time Frame: 21 months ]
  • 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.
  • 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.
  • Change in dysarthria and deglutition outcome evaluated by the maximum phonation time [ Time Frame: 21 months ]
  • 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.
  • 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.
  • Change in other movement disorder evaluated by the Clinical global impression (CGI) scale [ Time Frame: 21 months ]
  • 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.
  • Cognitive evaluation using the Mini Mental Status Examination (MMSE) [ Time Frame: Screening visit ]
    The MMSE is a brief 30-point questionnaire test commonly used to screen for dementia.
  • Cognitive evaluation using the Frontal Assessment Battery (FAB) [ Time Frame: Screening visit ]
    The FAB is a brief tool used to assess dysexecutive symptoms.
  • Cognitive evaluation using the BDI-II (Beck Depression Inventory) [ Time Frame: Screening visit ]
    The BDI-II is a self- report inventory for measuring the severity of depression.
  • Cognitive evaluation using the similarities and matrix reasoning tests from the Wechsler Adult Intelligence Scale (WAIS-IV) [ Time Frame: Pre-surgery visit ]
    The test of similarities measures concrete, functional, and abstract concept formation. The test of matrix reasoning measures nonverbal analytical reasoning.
  • Cognitive evaluation using the Modified Card Sorting Test (MCST) [ Time Frame: Pre-surgery visit ]
    The MCST assess problem solving and the ability to shift cognitive strategies in response to changing environmental contingencies.
  • Cognitive evaluation using the Trail Making Test (TMT) [ Time Frame: Pre-surgery visit ]
    The TMT assess visuo-motor speed and task switching abilities.
  • Cognitive evaluation using the phonemic verbal fluency task [ Time Frame: Pre-surgery visit ]
    The phonemic verbal fluency task assesses intrinsic response generation.
  • Cognitive evaluation using the 16-items free and cued recall test (RL/RI 16-items) [ Time Frame: Pre-surgery visit ]
    The RL/RI 16-items test assesses episodic memory and especially abilities to retrieve information from memory.
  • 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.
  • 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.
  • 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.
  • Change in dysarthria and deglutition outcome evaluated by the spontaneous speech and reading [ Time Frame: 21 months ]
  • 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.
  • 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.
  • Change in dysarthria and deglutition outcome evaluated by the maximum phonation time [ Time Frame: 21 months ]
  • 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.
  • Change in dysarthria and deglutition outcome evaluated by the De

    Information By: Hospices Civils de Lyon

    Dates:
    Date Received: September 11, 2015
    Date Started: January 2016
    Date Completion: September 2021
    Last Updated: September 30, 2016
    Last Verified: September 2016