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WILSTIM - DBS (WILson STIMulation - Deep Brain Stimulation) (WILSTIM DBS)

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ClinicalTrials.gov Identifier: NCT02552628
Recruitment Status : Recruiting
First Posted : September 17, 2015
Last Update Posted : July 12, 2018
Sponsor:
Information provided by (Responsible Party):
Hospices Civils de Lyon

Tracking Information
First Submitted Date  ICMJE September 11, 2015
First Posted Date  ICMJE September 17, 2015
Last Update Posted Date July 12, 2018
Actual Study Start Date  ICMJE January 2016
Estimated Primary Completion Date January 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 16, 2015)
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 Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 17, 2015)
  • 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.
  • 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).
  • Change in dysarthria and deglutition outcome evaluated by the timed test of swallowing capacity [ Time Frame: 21 months ]
  • 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.
  • Tolerance of Deep Brain Stimulation: occurrence of serious adverse events [ Time Frame: 23 months ]
    Clinical examination focusing specifically on vital signs.
Original Secondary Outcome Measures  ICMJE
 (submitted: September 16, 2015)
  • 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 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).
  • Change in dysarthria and deglutition outcome evaluated by the timed test of swallowing capacity [ Time Frame: 21 months ]
  • 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.
  • Tolerance of Deep Brain Stimulation: occurrence of serious adverse events [ Time Frame: 23 months ]
    Clinical examination focusing specifically on vital signs.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE WILSTIM - DBS (WILson STIMulation - Deep Brain Stimulation)
Official Title  ICMJE 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 Description 4 periods of stimulation on and off, sequence randomized at Day 0.
Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double (Participant, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Severe Dystonia
  • Wilson's Disease
Intervention  ICMJE
  • Device: Medtronic, Activa® PC "on"
  • Device: Medtronic, Activa® PC "off"
Study Arms  ICMJE
  • Experimental: Stimulation "on"
    The deep brain stimulation is "on"
    Intervention: Device: Medtronic, Activa® PC "on"
  • Sham Comparator: Stimulation "off"
    The deep brain stimulation is "off"
    Intervention: Device: Medtronic, Activa® PC "off"
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: September 16, 2015)
5
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE January 2022
Estimated Primary Completion Date January 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 60 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Stéphane THOBOIS, MD +33 4 72 35 72 18 stephane.thobois@chu-lyon.fr
Contact: Segolene GAILLARD +33 4 72 35 75 51 segolene.gaillard@chu-lyon.fr
Listed Location Countries  ICMJE France
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02552628
Other Study ID Numbers  ICMJE 69HCL14_0448
IDRCB ( Other Identifier: 2015-A00211-48 )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Hospices Civils de Lyon
Study Sponsor  ICMJE Hospices Civils de Lyon
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Stéphane THOBOIS, MD Hospices Civils de Lyon
PRS Account Hospices Civils de Lyon
Verification Date July 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP