Severe DystoniaWILSTIM DBSNCT02552628

WILSTIM - DBS (WILson STIMulation - Deep Brain Stimulation)

A study testing Medtronic, Activa® PC "on" and Medtronic, Activa® PC "off" in people with Severe Dystonia and Wilson's Disease, run by Hospices Civils de Lyon at 3 sites in France.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 to 60 years
Conditions the study is for: Severe Dystonia, Wilson's Disease
What is being tested?: Medtronic, Activa® PC "on" and Medtronic, Activa® PC "off"
Type of treatment: Medical device
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 5 participants
Where: 3 sitesFrance
Study dates: Jan 2016to 20 Jul 2022
Phase: Interventional
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 60 years
All sexes
No healthy volunteers
Adult

Who may be able to join

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)

Who cannot join

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.

Trial locations and contacts

3 sites in 1 country.

France3 sites

Hospices Civils de Lyon
Lyon
Hopital Lariboisiere
Paris
Hôpital Fondation Adolphe de Rothschild Paris
Paris

Other trials in France

About this study

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

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.

Read the detailed description

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

Conditions: Severe Dystonia, Wilson's Disease
Being tested: Medtronic, Activa® PC "on", Medtronic, Activa® PC "off"
Keywords: Wilson's Disease, Deep Brain Stimulation, dystonia
Medical subject headings: Dystonia, Hepatolenticular Degeneration

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Medtronic, Activa® PC "on"Device
Medtronic, Activa® PC "off"Device

Study groups in NCT02552628
Study group	Role	What they receive
Stimulation "on"	Experimental	The deep brain stimulation is "on" Receives: Device: Medtronic, Activa® PC "on"
Stimulation "off"	Sham comparator	The deep brain stimulation is "off" Receives: Device: Medtronic, Activa® PC "off"

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 21 months

Secondary outcomes (23)

Other movement disorder will be assessed by the reduction of the Burke-Fahn-Marsden (BFM) dystonia scale score
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.
Measured: 21 months
Change in other movement disorder evaluated by the Clinical global impression (CGI) scale
Measured: 21 months
Change in other movement disorder evaluated by the Unified Wilson Disease Rate Scale (UWDRS)
The UWDRS consists of 3 sections, including: consciousness, a historical review based on the Barthel scale, and neurological examination.
Measured: 21 months
Cognitive evaluation using the Mini Mental Status Examination (MMSE)
The MMSE is a brief 30-point questionnaire test commonly used to screen for dementia.
Measured: Screening visit (2 days)
Cognitive evaluation using the Frontal Assessment Battery (FAB)
The FAB is a brief tool used to assess dysexecutive symptoms.
Measured: Screening visit (2 days)
Cognitive evaluation using the BDI-II (Beck Depression Inventory)
The BDI-II is a self- report inventory for measuring the severity of depression.
Measured: Screening visit (2 days)
Cognitive evaluation using the similarities and matrix reasoning tests from the Wechsler Adult Intelligence Scale (WAIS-IV)
The test of similarities measures concrete, functional, and abstract concept formation. The test of matrix reasoning measures nonverbal analytical reasoning.
Measured: Pre-surgery visit (2 days)
Cognitive evaluation using the Modified Card Sorting Test (MCST)
The MCST assess problem solving and the ability to shift cognitive strategies in response to changing environmental contingencies.
Measured: Pre-surgery visit (2 days)
Cognitive evaluation using the Trail Making Test (TMT)
The TMT assess visuo-motor speed and task switching abilities.
Measured: Pre-surgery visit (2 days)
Cognitive evaluation using the phonemic verbal fluency task
The phonemic verbal fluency task assesses intrinsic response generation.
Measured: Pre-surgery visit (2 days)
Cognitive evaluation using the 16-items free and cued recall test (RL/RI 16-items)
The RL/RI 16-items test assesses episodic memory and especially abilities to retrieve information from memory.
Measured: Pre-surgery visit (2 days)
Change in cognitive outcome evaluated by the Tasks of the test of Attentional Performance (TAP)
The TAP is a normalized computerized battery to assess attentional and executive abilities.
Measured: 21 months
Change in behavioral and neuropsychiatric outcome evaluated by the "Inventaire du Syndrome Dysexécutif Comportemental" (ISDC)
The ISDC assesses behavioral dysexecutive symptoms.
Measured: 21 months
Change in behavioral and neuropsychiatric outcome evaluated by the Brief Psychiatric Rating Scale with anchor (BPRS-E(A))
The BPRS-E(A) is widely used to measure psychiatric symptoms and unusual behavior.
Measured: 21 months
Change in dysarthria and deglutition outcome evaluated by the spontaneous speech and reading
Measured: 21 months
Change in dysarthria and deglutition outcome evaluated by the the "Batterie d'Evaluation de la Dysarthrie" (BECD)
This BECD score provides a global assessment of dysarthria severity.
Measured: 21 months
Change in dysarthria and deglutition outcome evaluated by the Voice Handicap Index (VHI)
The VHI is a questionnaire to quantify the functional, physical and emotional impacts of a voice disorder on a patient's quality of life.
Measured: 21 months
Change in dysarthria and deglutition outcome evaluated by the maximum phonation time
Measured: 21 months
Change in dysarthria and deglutition outcome evaluated by the GRBAS (Grade, Roughness, Breathiness, Asthenia, Strain) scale
Auditory-perceptual evaluation method for hoarseness is the GRBAS scale of the Japan Society of Logopedics and Phoniatrics, which rates hoarseness.
Measured: 21 months
Change in dysarthria and deglutition outcome evaluated by the Deglutition Handicap Index (DHI)
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).
Measured: 21 months
Change in dysarthria and deglutition outcome evaluated by the timed test of swallowing capacity
Measured: 21 months
Change in social outcome evaluated by the Zarit Burden Inventory (ZBI)
The ZBI is a popular caregiver self-report measure used by many aging agencies.
Measured: 21 months
Tolerance of Deep Brain Stimulation: occurrence of serious adverse events
Clinical examination focusing specifically on vital signs.
Measured: 23 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jan 201620 Jul 2022

First posted17 Sep 2015 (estimated)
Study startJan 2016
Primary completion20 Jul 2022
Study completion20 Jul 2022

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Severe DystoniaStudies of the same condition, open and under way.
More trials run by Hospices Civils de LyonThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase N/A
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: Double blind
Who is masked: Participant, Outcomes assessor
Enrolment: 5 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02552628
Sponsor's protocol ID: 69HCL14_0448
Other IDs: IDRCB
Acronym: WILSTIM DBS
Status last verified: Jun 2023
First submitted: 11 Sep 2015
Last updated: 22 Aug 2025
Results posted: No
Data monitoring committee: Yes

Publications

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.
PubMed 39468897

Study at a glance

From the registry record, last updated by the sponsor on 22 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: DEEP BRAIN STIMULATION FOR SEVERE DYSTONIA ASSOCIATED WITH WILSON'S DISEASE. A Prospective Multicenter Meta-analysis of Nof1 Trials
ClinicalTrials.gov ID: NCT02552628
Acronym / sponsor ID: WILSTIM DBS / 69HCL14_0448
Conditions: Severe Dystonia, Wilson's Disease
Keywords: Wilson's Disease, Deep Brain Stimulation, dystonia
Study type: Interventional
Recruitment status: Completed
Enrolment: 5 participants (actual)
Lead sponsor: Hospices Civils de LyonUniversity, hospital or other
Study start: Jan 2016 (actual)
Primary completion: 20 Jul 2022 (actual)
Study completion: 20 Jul 2022 (actual)
First posted: 17 Sep 2015 (estimated)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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 design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: Double blind (participant, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
Stimulation "on"	Experimental	Device: Medtronic, Activa® PC "on"The deep brain stimulation is "on"
Stimulation "off"	Sham comparator	Device: Medtronic, Activa® PC "off"The deep brain stimulation is "off"

Who may qualify

Ages: 18 to 60 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult

Key inclusion criteria (7 listed)

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).

Key exclusion criteria (8 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Medtronic, Activa® PC "on"	Device	Stimulation "on"
Medtronic, Activa® PC "off"	Device	Stimulation "off"

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.

23 secondary outcomes

Other movement disorder will be assessed by the reduction of the Burke-Fahn-Marsden (BFM) dystonia scale score
Time frame: 21 months
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
Cognitive evaluation using the Mini Mental Status Examination (MMSE)
Time frame: Screening visit (2 days)
Cognitive evaluation using the Frontal Assessment Battery (FAB)
Time frame: Screening visit (2 days)
Cognitive evaluation using the BDI-II (Beck Depression Inventory)
Time frame: Screening visit (2 days)
Cognitive evaluation using the similarities and matrix reasoning tests from the Wechsler Adult Intelligence Scale (WAIS-IV)
Time frame: Pre-surgery visit (2 days)
Cognitive evaluation using the Modified Card Sorting Test (MCST)
Time frame: Pre-surgery visit (2 days)
Cognitive evaluation using the Trail Making Test (TMT)
Time frame: Pre-surgery visit (2 days)
Cognitive evaluation using the phonemic verbal fluency task
Time frame: Pre-surgery visit (2 days)
Cognitive evaluation using the 16-items free and cued recall test (RL/RI 16-items)
Time frame: Pre-surgery visit (2 days)
Change in cognitive outcome evaluated by the Tasks of the test of Attentional Performance (TAP)
Time frame: 21 months
Change in behavioral and neuropsychiatric outcome evaluated by the "Inventaire du Syndrome Dysexécutif Comportemental" (ISDC)
Time frame: 21 months
Change in behavioral and neuropsychiatric outcome evaluated by the Brief Psychiatric Rating Scale with anchor (BPRS-E(A))
Time frame: 21 months
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
Change in dysarthria and deglutition outcome evaluated by the Voice Handicap Index (VHI)
Time frame: 21 months
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
Change in dysarthria and deglutition outcome evaluated by the Deglutition Handicap Index (DHI)
Time frame: 21 months
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
Tolerance of Deep Brain Stimulation: occurrence of serious adverse events
Time frame: 23 months

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 22 Aug 2025.
Results publication: PubMed 39468897Laurencin 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.

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Stéphane THOBOIS, MD principal investigator

Hospices Civils de Lyon

3 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A study testing Medtronic, Activa® PC "on" and Medtronic, Activa® PC "off" in people with Severe Dystonia and Wilson's Disease, run by Hospices Civils de Lyon at 3 sites in France.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 22 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in movement disorder evaluated by the Canadian Occupational Performance Measure (COPM) performance and satisfaction scores (time frame: 21 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02552628, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Aug 2025.