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

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.

Study Overview

• Status: Completed
• Conditions: Cervical Dystonia; Spasmodic Torticollis
• Intervention / Treatment: Device: rTMS

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • New Mexico
    • Albuquerque, New Mexico, United States, 87131
      • University of New Mexico

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

5

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of New Mexico
• Collaborators: University Health Network, Toronto; National Institute of Neurological Disorders and Stroke (NINDS); National Institutes of Health (NIH); Dystonia Coalition
• Investigators: Principal Investigator: Sarah Pirio Richardson, MD, University of New Mexico; Study Director: H.A. Jinnah, MD, Emory University

Publications and helpful links

General Publications

• Murase N, Rothwell JC, Kaji R, Urushihara R, Nakamura K, Murayama N, Igasaki T, Sakata-Igasaki M, Mima T, Ikeda A, Shibasaki H. Subthreshold low-frequency repetitive transcranial magnetic stimulation over the premotor cortex modulates writer's cramp. Brain. 2005 Jan;128(Pt 1):104-15. doi: 10.1093/brain/awh315. Epub 2004 Oct 13.
• Lefaucheur JP, Fenelon G, Menard-Lefaucheur I, Wendling S, Nguyen JP. Low-frequency repetitive TMS of premotor cortex can reduce painful axial spasms in generalized secondary dystonia: a pilot study of three patients. Neurophysiol Clin. 2004 Oct;34(3-4):141-5. doi: 10.1016/j.neucli.2004.07.003.
• Beck S, Houdayer E, Richardson SP, Hallett M. The role of inhibition from the left dorsal premotor cortex in right-sided focal hand dystonia. Brain Stimul. 2009 Oct;2(4):208-14. doi: 10.1016/j.brs.2009.03.004. Epub 2009 May 3.
• Breakefield XO, Blood AJ, Li Y, Hallett M, Hanson PI, Standaert DG. The pathophysiological basis of dystonias. Nat Rev Neurosci. 2008 Mar;9(3):222-34. doi: 10.1038/nrn2337.
• Pirio Richardson S, Tinaz S, Chen R. Repetitive transcranial magnetic stimulation in cervical dystonia: effect of site and repetition in a randomized pilot trial. PLoS One. 2015 Apr 29;10(4):e0124937. doi: 10.1371/journal.pone.0124937. eCollection 2015.

Study record dates

Study Major Dates

• Study Start: March 1, 2013
• Primary Completion (Actual): June 1, 2014
• Study Completion (Actual): June 1, 2014

Study Registration Dates

• First Submitted: May 9, 2013
• First Submitted That Met QC Criteria: May 17, 2013
• First Posted (Estimate): May 21, 2013

Study Record Updates

• Last Update Posted (Estimate): July 28, 2016
• Last Update Submitted That Met QC Criteria: June 16, 2016
• Last Verified: June 1, 2016

More Information

Terms related to this study

• Keywords: rTMS; cervical dystonia; torticollis
• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Movement Disorders; Dyskinesias; Dystonia; Dystonic Disorders; Torticollis
• Other Study ID Numbers: UNM 657; U54NS065701 (U.S. NIH Grant/Contract)