Identification of Optimal Stimulation Site for Cervical Dystonia Symptoms: An Exploratory Study

Study Overview
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Brief Summary
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The overall objective of this application is to therapeutically target the dysfunctional premotor-motor interaction in dystonia-and to provide a focused treatment of specific anatomical networks in order to reduce side effects and to improve symptom control over conventional therapies.

Detailed Description
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We propose using repetitive transcranial magnetic stimulation (rTMS) over distinct premotor areas in patients with cervical dystonia (CD) with the goal of improving symptoms and reducing unwanted side effects. The knowledge gained in this proposed research will identify a specific premotor area to be targeted with rTMS that is expected to result in a novel intervention that could enhance or replace current treatments for CD. rTMS could be included as an adjunct treatment to botulinum toxin that could sustain treatment effect and decrease the frequency of re-injection, potentially resulting in cost savings without a decrease in symptom control. In addition to medical cost reduction, improved quality of life could be expected with the successful development of therapies that extend dystonia symptom control. rTMs has been FDA-approved for the treatment of depression and our proposal uses an even lower stimulation rate, suggesting continued use within clearly safe parameters. Successful completion of this research could lead to rapid adoption of this therapeutic modality. We will test the hypothesis that rTMS of a distinct premotor site will provide more effective treatment of CD than non-specific activation of the entire premotor region. This will be done by performing a randomized, observer-blinded exploratory pilot study to determine the optimal site of rTMS over various sites of the premotor and motor cortex to improve the symptoms of cervical dystonia. Completion of this aim should lead to development of targeted TMS therapy for CD.

Official Title
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Identification of Optimal Stimulation Site for Cervical Dystonia Symptoms: An Exploratory Study

Conditions
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Cervical Dystonia, Spasmodic Torticollis

Intervention / Treatment
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* Device: rTMS


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinical diagnosis of idiopathic cervical dystonia Age 18 years or older Normal findings in the medical history, physical and neurological examination, except for dystonia Last treatment with botulinum toxin more than two months ago Exclusion Criteria: History of seizure disorder Pregnancy- a pregnancy test will be performed for women of childbearing potential History of any other neurological disorders or conditions requiring the use of anti-depressants that are known to increase seizure threshold, neuroleptic medication, anticholinergic drugs and muscle relaxants History of neuroleptic medications/ prior use of neuroleptics

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 100 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Dorsal Premotor rTMS<br>0.2 Hz rTMS for 15 minutes | Device: rTMS<br> <br> |
| Active Comparator: Primary motor cortex rTMS<br>0.2 Hz rTMS for 15 minutes | Device: rTMS<br> <br> |
| Active Comparator: Supplemental Motor Area rTMS<br>0.2 Hz rTMS for 15 minutes | Device: rTMS<br> <br> |
| Active Comparator: Anterior Cingulate rTMS<br>0.2 Hz rTMS for 15 minutes | Device: rTMS<br> <br> |
| Sham Comparator: Sham rTMS<br>0.2 Hz rTMS for 15 minutes | Device: rTMS<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) | Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) was used to assess severity of disease. The score for this section ranges from 0 (absence of severity) to 35 (maximum severity). | Change from baseline pre-intervention TWSTRS score to post-intervention within 1 hour of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dorsal Premotor-motor Inhibition (dPMI) |  | Change from baseline dPMI to post-intervention within 1 hour of treatment | 
| Composite Measure of Patient Rating of Symptoms and Tolerability | This measure will confirm the intervention tolerability by the patient. He/she scored the tolerability from 0-10, 0 being completely tolerable and 10 completely intolerable. | Assessment completed immediately after rTMS treatment session | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cervical dystonia, torticollis, rTMS