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rTMS and Botulinum Toxin in Primary Cervical Dystonia

NCT ID: NCT02542839

Last Updated: 2023-12-22

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

9 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-11-30

Study Completion Date

2021-06-28

Brief Summary

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Primary cervical dystonia (PCD) is the most common form of focal dystonia. PCD is frequently reported as a source of disability, decreased quality of life, and social stigma. Botulinum toxin (BoNT) is the gold standard treatment for PCD. The average duration of benefits from BoNT injections was about 9.5 weeks and BoNT treatment is known to provide only pure symptomatic benefits and does not seem to modify the disease pathophysiology.

The investigator plans to use repetitive transcranial magnetic stimulation (rTMS) therapy as an adjunctive therapy in combination with BoNT injections as a novel approach to treat PCD. The primary goal of this study is to compare standard treatment with BoNT versus BoNT combined with a two week course of rTMS.

Detailed Description

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rTMS refers to the application of transcranial magnetic stimulation (TMS) pulses to a specific target at predefined stimulation parameters. Repeated sessions of rTMS therapy have been demonstrated to induce cumulative persistent benefits that can last weeks after the conclusion of the rTMS sessions

The central hypothesis of this study is that rTMS therapy in PCD can potentiate the effects of BoNT injections. With the current standard treatment, the peak-dose benefits seen with BoNT are seen at about 4-6 weeks after the administration of injections. The investigator will introduce a 1 week course of rTMS around 2-8 weeks before or after BoNT or T1). The investigator will examine the effects of combined therapy at 10 weeks after BoNT and 12 weeks after BoNT injections follow-up.

Conditions

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Primary Cervical Dystonia Dystonia

Keywords

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Botulinum Toxin Transcranial Magnetic Stimulation

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Outcome Assessors

Study Groups

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Real rTMS Stimulation

Repetitive TMS will be delivered over each cerebellar hemisphere, using a NeuroStar TMS therapy system. The coil will be positioned 3 cm lateral to the inion on the line joining the inion and the external auditory meatus. The coil position will be marked on the skin. 900 pulses will be delivered consecutively to each side with a frequency of 1 Hz and at an intensity of 90% of the resting motor threshold (RMT) for a total duration of 15 min for each cerebellar hemisphere. The RMT will be defined as the lowest stimulation intensity required to evoke a 50 μV potential in a target muscle. Constant coil position will be continuously monitored during the experiment. A similar protocol will be observed for the contralateral cerebellum. In addition, this group will have the following performed: Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) test, Cerebellar-brain Inhibition (CBI) measurement, and Craniocervical Dystonia Questionnaire (CDQ-24) questionnaire to fill out.

Group Type EXPERIMENTAL

NeuroStar TMS therapy

Intervention Type DEVICE

Application of repetitious transcranial magnetic stimulation (TMS) pulses using NeuroStar device to a specific brain target at predefined stimulation parameters.

Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS)

Intervention Type OTHER

All participants will receive a clinical assessment of dystonia severity by using the TWSTRS test.

Craniocervical Dystonia Questionnaire (CDQ-24)

Intervention Type OTHER

All participants will fill out the Craniocervical Dystonia Questionnaire (CDQ-24) quality of life questionnaire.

Cerebellar-brain Inhibition (CBI)

Intervention Type OTHER

All participants will have a measure of the cerebellar-brain inhibition(CBI) which will be conducted by using a TMS device determining the ability of the coil to activate the cerebellum.

Botulinum toxin injections

Intervention Type PROCEDURE

All participants will receive Botulinum toxin(BoNT) injections as part of their standard of care

Sham rTMS Stimulation

Patients will undergo the same procedure for identifying stimulus location used in patients receiving real rTMS. Simulated rTMS will be administered using sham NeuroStar TMS therapy system coil which produces discharge noise and vibration without stimulating the cerebral cortex. This technique has been suggested to provide more effective blinding compared to other methods use in previous controlled studies. In addition, this group will have the following performed: Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) test, Cerebellar-brain Inhibition (CBI) measurement, and Craniocervical Dystonia Questionnaire (CDQ-24) questionnaire to fill out.

Group Type SHAM_COMPARATOR

Sham NeuroStar TMS therapy

Intervention Type DEVICE

Same procedure as real rTMS without stimulating the cerebral cortex.

Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS)

Intervention Type OTHER

All participants will receive a clinical assessment of dystonia severity by using the TWSTRS test.

Craniocervical Dystonia Questionnaire (CDQ-24)

Intervention Type OTHER

All participants will fill out the Craniocervical Dystonia Questionnaire (CDQ-24) quality of life questionnaire.

Cerebellar-brain Inhibition (CBI)

Intervention Type OTHER

All participants will have a measure of the cerebellar-brain inhibition(CBI) which will be conducted by using a TMS device determining the ability of the coil to activate the cerebellum.

Botulinum toxin injections

Intervention Type PROCEDURE

All participants will receive Botulinum toxin(BoNT) injections as part of their standard of care

Interventions

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NeuroStar TMS therapy

Application of repetitious transcranial magnetic stimulation (TMS) pulses using NeuroStar device to a specific brain target at predefined stimulation parameters.

Intervention Type DEVICE

Sham NeuroStar TMS therapy

Same procedure as real rTMS without stimulating the cerebral cortex.

Intervention Type DEVICE

Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS)

All participants will receive a clinical assessment of dystonia severity by using the TWSTRS test.

Intervention Type OTHER

Craniocervical Dystonia Questionnaire (CDQ-24)

All participants will fill out the Craniocervical Dystonia Questionnaire (CDQ-24) quality of life questionnaire.

Intervention Type OTHER

Cerebellar-brain Inhibition (CBI)

All participants will have a measure of the cerebellar-brain inhibition(CBI) which will be conducted by using a TMS device determining the ability of the coil to activate the cerebellum.

Intervention Type OTHER

Botulinum toxin injections

All participants will receive Botulinum toxin(BoNT) injections as part of their standard of care

Intervention Type PROCEDURE

Eligibility Criteria

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Inclusion Criteria

* Diagnosis of PCD in accordance with the Consensus Statement of the Movement Disorder Society
* Subjects who report Botulinum Toxin benefits lasting 10 weeks or less only (suboptimal benefits with standard care)

Exclusion Criteria

* Pregnancy
* Active seizure disorder
* Presence of a metallic body such as pacemaker, implants, metal rods and hearing aid.
Minimum Eligible Age

30 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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American Brain Foundation

OTHER

Sponsor Role collaborator

Neuronetics

OTHER

Sponsor Role collaborator

University of Florida

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Aparna Wagle-Shukla, M.D.

Role: PRINCIPAL_INVESTIGATOR

UF Center for Movement Disorders and Neurorestoration

Locations

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UF Center for Movement Disorders & Neurorestoration

Gainesville, Florida, United States

Site Status

UF Brain Institute

Gainesville, Florida, United States

Site Status

Countries

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United States

References

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Tarsy D, Simon DK. Dystonia. N Engl J Med. 2006 Aug 24;355(8):818-29. doi: 10.1056/NEJMra055549. No abstract available.

Reference Type BACKGROUND
PMID: 16928997 (View on PubMed)

Phukan J, Albanese A, Gasser T, Warner T. Primary dystonia and dystonia-plus syndromes: clinical characteristics, diagnosis, and pathogenesis. Lancet Neurol. 2011 Dec;10(12):1074-85. doi: 10.1016/S1474-4422(11)70232-0. Epub 2011 Oct 24.

Reference Type BACKGROUND
PMID: 22030388 (View on PubMed)

Jankovic J. Treatment of dystonia. Lancet Neurol. 2006 Oct;5(10):864-72. doi: 10.1016/S1474-4422(06)70574-9.

Reference Type BACKGROUND
PMID: 16987733 (View on PubMed)

Dressler D, Tacik P, Saberi FA. Botulinum toxin therapy of cervical dystonia: duration of therapeutic effects. J Neural Transm (Vienna). 2015 Feb;122(2):297-300. doi: 10.1007/s00702-014-1253-8. Epub 2014 Jul 23.

Reference Type BACKGROUND
PMID: 25052566 (View on PubMed)

Thenganatt MA, Jankovic J. Treatment of dystonia. Neurotherapeutics. 2014 Jan;11(1):139-52. doi: 10.1007/s13311-013-0231-4.

Reference Type BACKGROUND
PMID: 24142590 (View on PubMed)

Hallett M. Transcranial magnetic stimulation: a primer. Neuron. 2007 Jul 19;55(2):187-99. doi: 10.1016/j.neuron.2007.06.026.

Reference Type BACKGROUND
PMID: 17640522 (View on PubMed)

Lefaucheur JP, Andre-Obadia N, Antal A, Ayache SS, Baeken C, Benninger DH, Cantello RM, Cincotta M, de Carvalho M, De Ridder D, Devanne H, Di Lazzaro V, Filipovic SR, Hummel FC, Jaaskelainen SK, Kimiskidis VK, Koch G, Langguth B, Nyffeler T, Oliviero A, Padberg F, Poulet E, Rossi S, Rossini PM, Rothwell JC, Schonfeldt-Lecuona C, Siebner HR, Slotema CW, Stagg CJ, Valls-Sole J, Ziemann U, Paulus W, Garcia-Larrea L. Evidence-based guidelines on the therapeutic use of repetitive transcranial magnetic stimulation (rTMS). Clin Neurophysiol. 2014 Nov;125(11):2150-2206. doi: 10.1016/j.clinph.2014.05.021. Epub 2014 Jun 5.

Reference Type BACKGROUND
PMID: 25034472 (View on PubMed)

Wagle Shukla A, Vaillancourt DE. Treatment and physiology in Parkinson's disease and dystonia: using transcranial magnetic stimulation to uncover the mechanisms of action. Curr Neurol Neurosci Rep. 2014 Jun;14(6):449. doi: 10.1007/s11910-014-0449-5.

Reference Type BACKGROUND
PMID: 24771105 (View on PubMed)

Rossi S, Ferro M, Cincotta M, Ulivelli M, Bartalini S, Miniussi C, Giovannelli F, Passero S. A real electro-magnetic placebo (REMP) device for sham transcranial magnetic stimulation (TMS). Clin Neurophysiol. 2007 Mar;118(3):709-16. doi: 10.1016/j.clinph.2006.11.005. Epub 2006 Dec 22.

Reference Type BACKGROUND
PMID: 17188568 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

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IRB201500341

Identifier Type: -

Identifier Source: org_study_id