Clinical trial NCT04910581: rTMS in Wilson Disease Dysarthria
Official title: Inhibitory rTMS Applied on Laryngeal Motor Cortex in Wilson's Disease Patients With Dysarthria
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Wilson Disease
Keywords: dyasarthria, repetitive transcranial magnetic stimulation
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2021-06-02
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention 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.
Primary purpose: TREATMENT

Brief 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. 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.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Improvement of the Clinical Assessment Battery for Dysarthria intelligibility score
timeFrame: within 30 minutes after stimulation session at Day1 and Day4
Secondary outcomes:
measure: Improvement of the Clinical Assessment Battery for Dysarthria intelligibility sub-scores
timeFrame: within 30 minutes after stimulation session at Day1 and Day4
measure: the "A" phonation time
timeFrame: within 30 minutes after stimulation session at Day1 and Day4
measure: Improvement of the diadococinesia
timeFrame: within 30 minutes after stimulation session at Day1 and Day4
measure: Improvement of text reading
timeFrame: within 30 minutes after stimulation session at Day1 and Day4
measure: Improvement of bucco-linguo-facial motricity
timeFrame: within 30 minutes after stimulation session at Day1 and Day4
measure: Improvement bucco-linguo-facial motricity
timeFrame: within 30 minutes after stimulation session at Day1 and Day4
measure: Correlation between clinical Assessment Battery for Dysarthria intelligibility score and UWDRS, and MRI brain atrophy and basal ganglia lesions
timeFrame: at Day1 and Day4
measure: Side effects of rTMS
timeFrame: within few hours after stimulation session at Day1 and Day4
Other outcomes:
Locations:
city: Paris
country: France
facility: Service de Physiologie Clinique-Explorations Fonctionnelles, AP-HP, Hôpital Lariboisière
city: Paris
country: France
facility: Service de Neurologie, Hopital Fondation Adolphe de Rothschild
Study officials:
References: