rTMS in Wilson Disease Dysarthria

Wilson Disease Clinical Trial

— WILSTIM2  

Official title:

Inhibitory rTMS Applied on Laryngeal Motor Cortex in Wilson's Disease Patients With Dysarthria

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04910581
• Other study ID #: D20180404
• Status: Completed
• Phase: N/A
• Start date: January 23, 2023
• Est. completion date: January 12, 2024

Study information

• Verified date: February 2024
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 18
• Est. completion date: January 12, 2024
• Est. primary completion date: January 12, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Dysarthria
• Wilson Disease

Intervention

Procedure:
• rTMS
Single 30-minutes session of 1Hz rTMS applied over the left laryngeal motor cortex
• Sham stimulation
Single 30-minutes session of sham stimulation applied over the left laryngeal motor cortex

Locations

Country	Name	City	State
France	Service de Neurologie, Hopital Fondation Adolphe de Rothschild	Paris
France	Service de Physiologie Clinique-Explorations Fonctionnelles, AP-HP, Hôpital Lariboisière	Paris

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	within 30 minutes after stimulation session at Day1 and Day4
Secondary	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	within 30 minutes after stimulation session at Day1 and Day4
Secondary	the "A" phonation time	Improvement of the "A" phonation time with active stimulation in comparison to sham stimulation	within 30 minutes after stimulation session at Day1 and Day4
Secondary	Improvement of the diadococinesia	Improvement of the diadococinesia with active stimulation in comparison to sham stimulation	within 30 minutes after stimulation session at Day1 and Day4
Secondary	Improvement of text reading	Improvement of text reading with active stimulation in comparison to sham stimulation	within 30 minutes after stimulation session at Day1 and Day4
Secondary	Improvement of bucco-linguo-facial motricity	Improvement of bucco-linguo-facial motricity with active stimulation in comparison to sham stimulation	within 30 minutes after stimulation session at Day1 and Day4
Secondary	Improvement bucco-linguo-facial motricity	Improvement bucco-linguo-facial motricity with active stimulation in comparison to sham stimulation	within 30 minutes after stimulation session at Day1 and Day4
Secondary	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)	at Day1 and Day4
Secondary	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.	within few hours after stimulation session at Day1 and Day4