Wilson DiseaseWILSTIM2NCT04910581
rTMS in Wilson Disease Dysarthria
A study testing rTMS in people with Wilson Disease, run by Assistance Publique - Hôpitaux de Paris at 2 sites in France.
Trial summary
Wilson disease is a hereditary hepatic and neurological disease associated with copper accumulation. Neurological symptoms are of extra-pyramidal, cerebellar and dystonic origin. Dysarthria is one of the debilitating symptoms of Wilson disease poorly responsive to pharmacological treatment. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Wilson Disease
- What is being tested?
- rTMS
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 18 participants
- Where
- 2 sitesFrance
- Study dates
- 23 Jan 2023to 12 Jan 2024
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Conseting adult patients with social insurance
- Wilson disease with dystonic hyperkinetic dysarthria
- Stable pharmacological therapy n the last 6 monts
- Brain MRI in the previous 6 months, without additional brain lesion
- Patients that did not receive botulinium toxin in the previous 4 months
Who cannot join
- Incapacitated adult
- Previous mdedical history of epilepsia
- Pregnancy or breastfeeding
- Brain lesion outside basal ganglia on brain MRI
- Patient consider by the investigator not able to sustain an 30 minutes rTMS session without moving
- Vocal chord lesion
- Previous history of laryngeal surgery
- rTMS contra indication
Trial locations and contacts
2 sites in 1 country.
France2 sites
Service de Physiologie Clinique-Explorations Fonctionnelles, AP-HP, Hôpital Lariboisière
Paris, 75010
Service de Neurologie, Hopital Fondation Adolphe de Rothschild
Paris, 75019
About this study
Official title: Inhibitory rTMS Applied on Laryngeal Motor Cortex in Wilson's Disease Patients With Dysarthria
Wilson disease is a hereditary hepatic and neurological disease associated with copper accumulation. Neurological symptoms are of extra-pyramidal, cerebellar and dystonic origin. Dysarthria is one of the debilitating symptoms of Wilson disease poorly responsive to pharmacological treatment. The most common form is a dystonic hyperkinetic Dysarthria.
Pathophysiology of dystonia is still not elucidated. Motor cortex hyperexcitability has been demonstrated in various forms of dystonia. Furthermore, rTMS inhibitory applied over motor cortex has been shown to transitory reduce dystonic symptoms in various forms of dystonia.
In the present study, we investigate the effect of a single 1Hz 20-minutes inhibitory rTMS session applied over the motor laryngeal cortex on dyasarthria is the main kinetic dysarthria has been shown to be associated with inhibition of laryngeal motor cortex in Parkinson disease.
Read the detailed description
A consecutive series of Wilson disease patients with dystonic hyperkinetic dysarthria will be prospectively recruited.
Patients will receive 3 days apart to two rTMS sessions.
rTMS procedures will be performed with a figure of eight coiled. A single 20-minutes 1 Hz biphasic stimulation (1200 pulses) session will be applied over the laryngeal motor cortex. A brain imaging positioning device will be used during all the procedure A second stimulation session will be performed 3 days apart.
Patients will be centrally randomized to receive first either the active stimulation (80% of the resting motor threshold) or the sham stimulation (using a visually identical coil to reproduce the click sound and the scalp sensation of the active coil).
A TMS evaluation of cortical silent period over the left motor cortex will be performed before the first rTMS session.
Before and immediately after each stimulation (active or sham) patient will received an clinical evaluation including Clinical Assessment Battery for Dysarthria intelligibility score, "A" phonation time, diadococinesia , bucco-linguo-facial motricity score and UWDRS.
A standard 20-minutes EEG will be performed before the first rTMS session and immediately after the second rTMS session.
- Conditions
- Wilson Disease
- Being tested
- rTMS, Sham stimulation
- Keywords
- dyasarthria, repetitive transcranial magnetic stimulation
- Medical subject headings
- Hepatolenticular Degeneration
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
rTMSProcedure or surgery
Single 30-minutes session of 1Hz rTMS applied over the left laryngeal motor cortex
Sham stimulationProcedure or surgery
Single 30-minutes session of sham stimulation applied over the left laryngeal motor cortex
| Study group | Role | What they receive |
|---|---|---|
| Experimental stimulation | Active comparator | Patients receive an inhibitor treatment of rTMS using activ coil (MCF B65 coil) for 30 minutes at 1Hz at 80% of the resting motor threshold (MagPro stimulator; MagVenture A / S, Farum, Denmark) onto the left laryngeal cortex located thanks to a neuronavigation device (Syneika one [SYN1], Syneika, Cesson-Sévigné, France). Receives: Procedure: rTMS |
| Sham stimulation | Placebo comparator | Patients receive a treatment of rTMS using placebo coil (MCF P B65 coil) for 30 minutes at 1Hz (MagPro stimulator; MagVenture A / S, Farum, Denmark) onto the left laryngeal cortex located thanks to a neuronavigation device (Syneika one [SYN1], Syneika, Cesson-Sévigné, France). Receives: Procedure: Sham stimulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Improvement of the Clinical Assessment Battery for Dysarthria intelligibility score
Improvement of the Clinical Assessment Battery for Dysarthria intelligibility score with active stimulation in comparison to sham stimulation
Measured: within 30 minutes after stimulation session at Day1 and Day4
Secondary outcomes (8)
Improvement of the Clinical Assessment Battery for Dysarthria intelligibility sub-scores
Improvement of the Clinical Assessment Battery for Dysarthria intelligibility sub-scores with active stimulation in comparison to sham stimulation
Measured: within 30 minutes after stimulation session at Day1 and Day4
the "A" phonation time
Improvement of the "A" phonation time with active stimulation in comparison to sham stimulation
Measured: within 30 minutes after stimulation session at Day1 and Day4
Improvement of the diadococinesia
Improvement of the diadococinesia with active stimulation in comparison to sham stimulation
Measured: within 30 minutes after stimulation session at Day1 and Day4
Improvement of text reading
Improvement of text reading with active stimulation in comparison to sham stimulation
Measured: within 30 minutes after stimulation session at Day1 and Day4
Improvement of bucco-linguo-facial motricity
Improvement of bucco-linguo-facial motricity with active stimulation in comparison to sham stimulation
Measured: within 30 minutes after stimulation session at Day1 and Day4
Improvement bucco-linguo-facial motricity
Improvement bucco-linguo-facial motricity with active stimulation in comparison to sham stimulation
Measured: within 30 minutes after stimulation session at Day1 and Day4
Correlation between clinical Assessment Battery for Dysarthria intelligibility score and UWDRS, and MRI brain atrophy and basal ganglia lesions
Correlation of changes in the Battery for Dysarthria intelligibility score with clinical parameters (age at diagnosis, delay related to first symptoms, degree of neurological handicap and brain lesions observed on basline MRI (cortical atrophy and lesions of the basal ganglia)
Measured: at Day1 and Day4
Side effects of rTMS
Any side effect after stimulation (fatigue, neck pain, neck stiffness, dizziness, nausea, itching, mood disorders ..) will be collected following the stimulation.
Side effects of rTMS are rare. Most often they are minor and transient.
Measured: within few hours after stimulation session at Day1 and Day4
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jun 2021
- Study start23 Jan 2023
- Primary completion12 Jan 2024
- Study completion12 Jan 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Wilson DiseaseStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe 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
- Model description
- After randomization, patients are to receive blindly the first rTMS session according to the arm (placebo or active). A second stimulation session is to be performed 3 days apart to apply the reverse arm.
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04910581
- Sponsor's protocol ID
- D20180404
- Acronym
- WILSTIM2
- Status last verified
- Feb 2024
- First submitted
- 14 May 2021
- Last updated
- 28 Feb 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Inhibitory rTMS Applied on Laryngeal Motor Cortex in Wilson's Disease Patients With Dysarthria
- ClinicalTrials.gov ID
- NCT04910581
- Acronym / sponsor ID
- WILSTIM2 / D20180404
- Conditions
- Wilson Disease
- Keywords
- dyasarthria, repetitive transcranial magnetic stimulation
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- 23 Jan 2023 (actual)
- Primary completion
- 12 Jan 2024 (actual)
- Study completion
- 12 Jan 2024 (actual)
- First posted
- 2 Jun 2021 (actual)
- 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.
Wilson disease is a hereditary hepatic and neurological disease associated with copper accumulation. Neurological symptoms are of extra-pyramidal, cerebellar and dystonic origin. Dysarthria is one of the debilitating symptoms of Wilson disease poorly responsive to pharmacological treatment. The most common form is a dystonic hyperkinetic Dysarthria.
Pathophysiology of dystonia is still not elucidated. Motor cortex hyperexcitability has been demonstrated in various forms of dystonia. Furthermore, rTMS inhibitory applied over motor cortex has been shown to transitory reduce dystonic symptoms in various forms of dystonia.
In the present study, we investigate the effect of a single 1Hz 20-minutes inhibitory rTMS session applied over the motor laryngeal cortex on dyasarthria is the main kinetic dysarthria has been shown to be associated with inhibition of laryngeal motor cortex in Parkinson disease.
Detailed description
A consecutive series of Wilson disease patients with dystonic hyperkinetic dysarthria will be prospectively recruited.
Patients will receive 3 days apart to two rTMS sessions.
rTMS procedures will be performed with a figure of eight coiled. A single 20-minutes 1 Hz biphasic stimulation (1200 pulses) session will be applied over the laryngeal motor cortex. A brain imaging positioning device will be used during all the procedure A second stimulation session will be performed 3 days apart.
Patients will be centrally randomized to receive first either the active stimulation (80% of the resting motor threshold) or the sham stimulation (using a visually identical coil to reproduce the click sound and the scalp sensation of the active coil).
A TMS evaluation of cortical silent period over the left motor cortex will be performed before the first rTMS session.
Before and immediately after each stimulation (active or sham) patient will received an clinical evaluation including Clinical Assessment Battery for Dysarthria intelligibility score, "A" phonation time, diadococinesia , bucco-linguo-facial motricity score and UWDRS.
A standard 20-minutes EEG will be performed before the first rTMS session and immediately after the second rTMS session.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
- Model description
- After randomization, patients are to receive blindly the first rTMS session according to the arm (placebo or active). A second stimulation session is to be performed 3 days apart to apply the reverse arm.
| Arm | Type | Receives |
|---|---|---|
| Experimental stimulation | Active comparator | Procedure: rTMSPatients receive an inhibitor treatment of rTMS using activ coil (MCF B65 coil) for 30 minutes at 1Hz at 80% of the resting motor threshold (MagPro stimulator; MagVenture A / S, Farum, Denmark) onto the left laryngeal cortex located thanks to a neuronavigation device (Syneika one [SYN1], Syneika, Cesson-Sévigné, France). |
| Sham stimulation | Placebo comparator | Procedure: Sham stimulationPatients receive a treatment of rTMS using placebo coil (MCF P B65 coil) for 30 minutes at 1Hz (MagPro stimulator; MagVenture A / S, Farum, Denmark) onto the left laryngeal cortex located thanks to a neuronavigation device (Syneika one [SYN1], Syneika, Cesson-Sévigné, France). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Conseting adult patients with social insurance
- Wilson disease with dystonic hyperkinetic dysarthria
- Stable pharmacological therapy n the last 6 monts
- Brain MRI in the previous 6 months, without additional brain lesion
- Patients that did not receive botulinium toxin in the previous 4 months
Key exclusion criteria (8 listed)
- Incapacitated adult
- Previous mdedical history of epilepsia
- Pregnancy or breastfeeding
- Brain lesion outside basal ganglia on brain MRI
- Patient consider by the investigator not able to sustain an 30 minutes rTMS session without moving
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 |
|---|---|---|
| rTMSSingle 30-minutes session of 1Hz rTMS applied over the left laryngeal motor cortex | Procedure or surgery | Experimental stimulation |
| Sham stimulationSingle 30-minutes session of sham stimulation applied over the left laryngeal motor cortex | Procedure or surgery | Sham stimulation |
Primary outcome
Improvement of the Clinical Assessment Battery for Dysarthria intelligibility score
Time frame: within 30 minutes after stimulation session at Day1 and Day4
Improvement of the Clinical Assessment Battery for Dysarthria intelligibility score with active stimulation in comparison to sham stimulation
8 secondary outcomes
Improvement of the Clinical Assessment Battery for Dysarthria intelligibility sub-scores
Time frame: within 30 minutes after stimulation session at Day1 and Day4
the "A" phonation time
Time frame: within 30 minutes after stimulation session at Day1 and Day4
Improvement of the diadococinesia
Time frame: within 30 minutes after stimulation session at Day1 and Day4
Improvement of text reading
Time frame: within 30 minutes after stimulation session at Day1 and Day4
Improvement of bucco-linguo-facial motricity
Time frame: within 30 minutes after stimulation session at Day1 and Day4
Improvement bucco-linguo-facial motricity
Time frame: within 30 minutes after stimulation session at Day1 and Day4
Correlation between clinical Assessment Battery for Dysarthria intelligibility score and UWDRS, and MRI brain atrophy and basal ganglia lesions
Time frame: at Day1 and Day4
Side effects of rTMS
Time frame: within few hours after stimulation session at Day1 and Day4
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 28 Feb 2024.
- Individual participant dataSharing planned: No
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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.
The record lists no contact. Use the official record to reach the sponsor.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing rTMS in people with Wilson Disease, run by Assistance Publique - Hôpitaux de Paris at 2 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 5 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 28 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 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?
Improvement of the Clinical Assessment Battery for Dysarthria intelligibility score (time frame: within 30 minutes after stimulation session at Day1 and Day4). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 28 Feb 2024.