Clinical trial NCT01859247: Identification of Optimal Stimulation Site for Cervical Dystonia Symptoms: An Exploratory Study
Official title: Identification of Optimal Stimulation Site for Cervical Dystonia Symptoms: An Exploratory Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Cervical Dystonia
Spasmodic Torticollis
Keywords: cervical dystonia
torticollis
rTMS
Lead sponsor: University of New Mexico
Sponsor class: OTHER
Collaborators: name: Dystonia Coalition
name: National Institutes of Health (NIH)
name: National Institute of Neurological Disorders and Stroke (NINDS)
name: University Health Network, Toronto
First posted: 2013-05-21
Enrollment: 8
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS)
timeFrame: Change from baseline pre-intervention TWSTRS score to post-intervention within 1 hour of treatment
Secondary outcomes:
measure: Dorsal Premotor-motor Inhibition (dPMI)
timeFrame: Change from baseline dPMI to post-intervention within 1 hour of treatment
measure: Composite Measure of Patient Rating of Symptoms and Tolerability
timeFrame: Assessment completed immediately after rTMS treatment session
Other outcomes:
Locations:
city: Albuquerque
country: United States
facility: University of New Mexico
state: New Mexico
Study officials:
affiliation: University of New Mexico
name: Sarah Pirio Richardson, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Emory University
name: H.A. Jinnah, MD
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.