Inhibitory rTMS in Dystonic Wilson Patients (WILSTIM)

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by Assistance Publique - Hôpitaux de Paris
Sponsor:
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier:
NCT01980433
First received: October 24, 2013
Last updated: April 11, 2014
Last verified: April 2014
  Purpose

Wilson disease is a genetic disorder resulting in copper accumulation in liver, brain and eye. The neurologic complications include dystonic syndrome, which is a prolonged and excessive muscle activation responsible for abnormal postures. Hand dystonia prevents daily life activities such as writing, which is particularly disabling, since writing is the only mean of communication in these patients with significant slurred speech. Treatment is limited and only partially effective.

Low frequency (<or=1Hz) repetitive transcranial magnetic stimulation (rTMS) has shown inhibiting properties when applied over the cortex. Since dystonia has been correlated to hyperactivation of the neurons of the somatosensory cortex (SSC), we hypothesize that one single 20-minute session of 1 Hz rTMS applied on left SSC will improve writing of the right dystonic hand, assessed immediately at the end of the session.


Condition Intervention
Wilson Disease
Movement Disorders
Repetitive Transcranial Magnetic Stimulation
Device: Repetitive Transcranial Magnetic Stimulation (rTMS)
Other: pre and post-rTMS electroencephalogram
Other: WCRS
Other: handwriting scale DPRE
Other: visual analog scale of discomfort writing and parameters collected on touchpad

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Study of Writing Improvement in Patients With Wilson Disease and Dystonia After One Session of Inhibitory Repetitive Transcranial Magnetic Stimulation

Resource links provided by NLM:


Further study details as provided by Assistance Publique - Hôpitaux de Paris:

Primary Outcome Measures:
  • immediate and significant improvement in writing [ Time Frame: up to 1 week ] [ Designated as safety issue: No ]

    Improvement of handwriting performance immediately after one single 20 minutes session of inhibitory (1 Hz) repetitive transcranial magnetic stimulation over the left somatosensory cortex.

    quantitative test score of writing WCRS

    Active or sham stimulation will be randomly assigned to the patient and the other session will be performed 3 days later.



Secondary Outcome Measures:
  • significant improvement in writing [ Time Frame: up to 1 week ] [ Designated as safety issue: No ]

    improvement of other quantitative test scores of writing (VAS subjective discomfort writing, DPRE scales and parameters measured on touchpad) after a single session of 1 Hz rTMS inhibitory to the left CSS , compared to the scores achieved in the 24 hours before the session of rTMS.

    Active or sham stimulation will be randomly assigned to the patient and the other session will be performed 3 days later.


  • improvement of dystonia on the scale WDRS [ Time Frame: up to 1 week ] [ Designated as safety issue: No ]

    Assessing the improvement of dystonia on the scale WDRS after a single session of 1 Hz rTMS inhibitory to the left CSS, compared to the scores achieved in the 24 hours before the session of rTMS.

    Active or sham stimulation will be randomly assigned to the patient and the other session will be performed 3 days later.


  • correlation between the scores and the other parameters of disease severity [ Time Frame: up to 1 week ] [ Designated as safety issue: No ]
    Assess whether age, disease duration and the presence of cortical atrophy are inversely correlated with the evolution of scores.


Estimated Enrollment: 15
Study Start Date: January 2014
Estimated Study Completion Date: February 2015
Estimated Primary Completion Date: February 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Active rTMS
Repetitive Transcranial Magnetic stimulation: 1 Hz rTMS, delivered to left somatosensory cortex during rest. Intervention is delivered during 20 minutes in one single session.
Device: Repetitive Transcranial Magnetic Stimulation (rTMS)
Inhibitory 1 Hz rTMS, delivered to left somatosensory cortex during rest. Intervention is delivered during 20 minutes in one single session.
Other: pre and post-rTMS electroencephalogram
to verify the absence of infraclinical seizures
Other: WCRS
Writer's cramp rating scale
Other: handwriting scale DPRE
handwriting in development and being evaluated by the NRC Wilson
Other: visual analog scale of discomfort writing and parameters collected on touchpad
Sham Comparator: Sham rTMS
Placebo Transcranial Magnetic stimulation delivered to left somatosensory cortex during rest. Intervention is delivered during 20 minutes in one single session.
Device: Repetitive Transcranial Magnetic Stimulation (rTMS)
Inhibitory 1 Hz rTMS, delivered to left somatosensory cortex during rest. Intervention is delivered during 20 minutes in one single session.
Other: pre and post-rTMS electroencephalogram
to verify the absence of infraclinical seizures
Other: WCRS
Writer's cramp rating scale
Other: handwriting scale DPRE
handwriting in development and being evaluated by the NRC Wilson
Other: visual analog scale of discomfort writing and parameters collected on touchpad

Detailed Description:

This study investigates the handwriting performance of an homogeneous cohort of patients with Wilson disease and right handed dystonia, after one single inhibitory repetitive transcranial magnetic stimulation (rTMS). Fifteen patients with focal right hand dystonia will receive randomly either active or sham rTMS (1 Hz) to the left somatosensory cortex (SSC) in one single 20 minutes session. Handwriting performance will be measured immediately after this unique session (Visual analogic scale of subjective discomfort in writing, DPRE and WCRS scales, pen pressure and pen velocity measured on touchpad), compared to scores obtained 24 hours before the session. Three days later, the patient will receive the other session (sham rTMS or active rTMS) and the same parameters will be evaluated.

This is a single-center, randomized, crossover, prospective, clinical and double-blind study (the rTMS session is performed by the neurophysiologist, but the patient and the neurologist who will perform the handwriting evaluation are blind to the session).

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Wilson disease with focal right hand dystonia
  • No modification of medical treatment for 6 months
  • No botulinum toxin administration within the past four months
  • Right handed
  • Focal right hand dystonia
  • Cerebral Magnetic Resonance performed the last 6 months with no other lesion than met in Wilson disease
  • Over 18
  • Insurance policy holder
  • Informed consent

Exclusion Criteria:

  • Pregnant woman
  • Guardianship procedure
  • Seizure history
  • Other cerebral lesions on cerebral MRI than met in Wilson Disease
  • Unable to stay quiet for 30 minutes
  • Handwriting impossible
  • Contra-indications to repetitive Transcranial Magnetic Stimulation
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01980433

Contacts
Contact: Nathalie KUBIS, MD, PhD 33 1 49 95 83 14/80 88 nathalie.kubis@lrb.aphp.fr
Contact: Jean-Marc TROCELLO, MD 33 1 49 95 63 44 jean-marc.trocello@lrb.aphp.fr

Locations
France
Hospital Lariboisiere Recruiting
Paris, Ile de France, France, 75010
Contact: Nathalie Kubis, PhD, MD    33 1 49 95 83 14/80 88    nathalie.kubis@lrb.aphp.fr   
Contact: Jean-Marc Trocello, MD    33 1 49 95 63 44    jean-marc.trocello@lrb.aphp.fr   
Principal Investigator: Nathalie KUBIS, PhD, MD         
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Investigators
Study Director: Nathalie KUBIS, MD, PhD Physiology Department, Lariboisière Hospital
Principal Investigator: Jean-Marc TROCELLO, MD Neurology, Lariboisière Hospital
  More Information

No publications provided

Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT01980433     History of Changes
Other Study ID Numbers: P121105
Study First Received: October 24, 2013
Last Updated: April 11, 2014
Health Authority: France: Ministry of Health

Keywords provided by Assistance Publique - Hôpitaux de Paris:
Wilson disease
Dystonia
Movement Disorders
Handwriting
Repetitive Transcranial Magnetic Stimulation

Additional relevant MeSH terms:
Hepatolenticular Degeneration
Movement Disorders
Liver Diseases
Digestive System Diseases
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Brain Diseases, Metabolic, Inborn
Brain Diseases, Metabolic
Heredodegenerative Disorders, Nervous System
Neurodegenerative Diseases
Genetic Diseases, Inborn
Metabolic Diseases
Metabolism, Inborn Errors
Metal Metabolism, Inborn Errors

ClinicalTrials.gov processed this record on July 29, 2014