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

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

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Severe Dystonia; Wilson's Disease	Device: Medtronic, Activa® PC "on"; Device: Medtronic, Activa® PC "off"	Not Applicable

Detailed Description:

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

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 5 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: DEEP BRAIN STIMULATION FOR SEVERE DYSTONIA ASSOCIATED WITH WILSON'S DISEASE. A Prospective Multicenter Meta-analysis of Nof1 Trials
• Actual Study Start Date: January 2016
• Estimated Primary Completion Date: January 2022
• Estimated Study Completion Date: January 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: Stimulation "on"; The deep brain stimulation is "on"	Device: Medtronic, Activa® PC "on"
Sham Comparator: Stimulation "off"; The deep brain stimulation is "off"	Device: Medtronic, Activa® PC "off"

Outcome Measures

Primary Outcome Measures :

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 Outcome Measures :

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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 60 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Contacts

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

Locations

France

Hospices Civils de Lyon; Recruiting

Lyon, France

Contact: Stéphane THOBOIS, MD +33 4 72 35 72 18 stephane.thobois@chu-lyon.fr

Hopital Lariboisiere; Recruiting

Paris, France

Contact: FRANCE WOIMANT

Principal Investigator: FRANCE WOIMANT

Sponsors and Collaborators

Hospices Civils de Lyon

Investigators

• Principal Investigator: Stéphane THOBOIS, MD; Hospices Civils de Lyon

More Information

• Responsible Party: Hospices Civils de Lyon
• ClinicalTrials.gov Identifier: NCT02552628
• Other Study ID Numbers: 69HCL14_0448; IDRCB ( Other Identifier: 2015-A00211-48 )
• First Posted: September 17, 2015
• Last Update Posted: July 12, 2018
• Last Verified: July 2018

Keywords provided by Hospices Civils de Lyon:

Wilson's Disease; Deep Brain Stimulation; dystonia

Additional relevant MeSH terms:

Hepatolenticular Degeneration; Dystonia; Dystonic Disorders; Dyskinesias; Neurologic Manifestations; Nervous System Diseases; Movement Disorders; Central Nervous System Diseases; Liver Diseases; Digestive System Diseases; Basal Ganglia Diseases; Brain Diseases; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Genetic Diseases, Inborn; Metabolism, Inborn Errors; Metal Metabolism, Inborn Errors; Metabolic Diseases