rTMS in Wilson Disease Dysarthria

NCT04910581 | Completed

• 1 other identifier: D20180404
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 2

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.

Conditions

Wilson Disease

Keywords

dyasarthria, repetitive transcranial magnetic stimulation

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (8)

• Improvement of the Clinical Assessment Battery for Dysarthria intelligibility sub-scores

  within 30 minutes after stimulation session at Day1 and Day4

• the "A" phonation time

  within 30 minutes after stimulation session at Day1 and Day4

• Improvement of the diadococinesia

  within 30 minutes after stimulation session at Day1 and Day4

• Improvement of text reading

  within 30 minutes after stimulation session at Day1 and Day4

• Improvement of bucco-linguo-facial motricity

  within 30 minutes after stimulation session at Day1 and Day4

Study Arms (2)

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).

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).

Procedure: Sham stimulation

Interventions

rTMS PROCEDURE

Single 30-minutes session of 1Hz rTMS applied over the left laryngeal motor cortex

Experimental stimulation

Sham stimulation PROCEDURE

Single 30-minutes session of sham stimulation applied over the left laryngeal motor cortex

Sham stimulation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (2)

Service de Physiologie Clinique-Explorations Fonctionnelles, AP-HP, Hôpital Lariboisière

Paris, 75010, France

Location

Service de Neurologie, Hopital Fondation Adolphe de Rothschild

Paris, 75019, France

Location

MeSH Terms

Conditions

Hepatolenticular Degeneration

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Movement Disorders; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolism, Inborn Errors; Metal Metabolism, Inborn Errors; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Masking Details: Patients are 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). The operator is unblided. The evaluator is blinded.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: May 14, 2021
• First Posted: June 2, 2021
• Study Start: January 23, 2023
• Primary Completion: January 12, 2024
• Study Completion: January 12, 2024
• Last Updated: February 28, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share

Locations

FR (2)