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NCT Number: NCT04910581

rTMS in Wilson Disease 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.

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Key information

Conditions

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

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Service de Neurologie, Hopital Fondation Adolphe de Rothschild, Paris, France

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

rTMS

Procedure

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

Sham stimulation

Procedure

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

Primary outcomes

  1. 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

Secondary outcomes

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

    Time frame: within 30 minutes after stimulation session at Day1 and Day4

    Improvement of the Clinical Assessment Battery for Dysarthria intelligibility sub-scores with active stimulation in comparison to sham stimulation

  2. the "A" phonation time

    Time frame: within 30 minutes after stimulation session at Day1 and Day4

    Improvement of the "A" phonation time with active stimulation in comparison to sham stimulation

  3. Improvement of the diadococinesia

    Time frame: within 30 minutes after stimulation session at Day1 and Day4

    Improvement of the diadococinesia with active stimulation in comparison to sham stimulation

  4. Improvement of text reading

    Time frame: within 30 minutes after stimulation session at Day1 and Day4

    Improvement of text reading with active stimulation in comparison to sham stimulation

  5. Improvement of bucco-linguo-facial motricity

    Time frame: within 30 minutes after stimulation session at Day1 and Day4

    Improvement of bucco-linguo-facial motricity with active stimulation in comparison to sham stimulation

  6. Improvement bucco-linguo-facial motricity

    Time frame: within 30 minutes after stimulation session at Day1 and Day4

    Improvement bucco-linguo-facial motricity with active stimulation in comparison to sham stimulation

  7. 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

    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)

  8. Side effects of rTMS

    Time frame: within few hours after stimulation session at Day1 and Day4

    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.

Sponsors and collaborators

Lead sponsor

Assistance Publique - Hôpitaux de Paris

Other

Registry information

Official study title

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

Acronym: WILSTIM2

Important dates

Study start
2023
Primary completion
2024
Study completion
2024
First posted
Jun 2, 2021
Registry last updated
Feb 28, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

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This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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