rTMS and Botulinum Toxin in Primary Cervical Dystonia

Dystonia Clinical Trial

Official title:

Combined Therapy With rTMS and Botulinum Toxin in Primary Cervical Dystonia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02542839
• Other study ID #: IRB201500341
• Status: Completed
• Phase: N/A
• Start date: November 2015
• Est. completion date: June 28, 2021

Study information

• Verified date: August 2023
• Source: University of Florida
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 9
• Est. completion date: June 28, 2021
• Est. primary completion date: June 28, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 30 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Dystonia
• Dystonic Disorders
• Primary Cervical Dystonia
• Torticollis

Intervention

Device:
• NeuroStar TMS therapy
Application of repetitious transcranial magnetic stimulation (TMS) pulses using NeuroStar device to a specific brain target at predefined stimulation parameters.
• Sham NeuroStar TMS therapy
Same procedure as real rTMS without stimulating the cerebral cortex.

Other:
• Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS)
All participants will receive a clinical assessment of dystonia severity by using the TWSTRS test.
• Craniocervical Dystonia Questionnaire (CDQ-24)
All participants will fill out the Craniocervical Dystonia Questionnaire (CDQ-24) quality of life questionnaire.
• 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.

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

Locations

Country	Name	City	State
United States	UF Brain Institute	Gainesville	Florida
United States	UF Center for Movement Disorders & Neurorestoration	Gainesville	Florida

Sponsors (3)

Lead Sponsor	Collaborator
University of Florida	American Brain Foundation, Neuronetics

Country where clinical trial is conducted

United States, 

References & Publications (9)

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. — View Citation

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

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

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. — View Citation

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. — View Citation

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. — View Citation

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

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

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dystonia Severity as Assessed by the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS)	A clinical assessment of dystonia severity will be conducted at each study visit using the TWSTRS. The TWSTRS is a widely accepted composite rating scale for PCD with subscales for clinical severity, functional disability, and associated pain. The total score reported here can range 0-85, where a higher scores represent greater dystonia severity.	absolute value at 12 weeks
Secondary	TMS Measure Referred to as Cerebellar Inhibition (CBI)	A measure of the cerebellar-brain inhibition(CBI) will be conducted using a TMS device determining the ability of the coil to activate the cerebellum. CBI is calculated by taking the mean of amplitudes of motor-evoked potentials (mV) in response to conditioned stimulation and dividing it by the mean of amplitudes of motor-evoked potentials (mV) in response to unconditioned stimulation (i.e., the control condition). Thus it is a measure of the degree of inhibition due to a conditioning stimulus, where <1 indicates inhibition, =1 indicates no inhibition, and >1 indicates not inhibition but excitation. As a ratio of amplitudes, it does not have units.	absolute value at 12 weeks
Secondary	Craniocervical Dystonia Questionnaire	The Craniocervical Dystonia Questionnaire (CDQ-24) is a patient-rated health related quality of life (HR-QoL) measure for craniocervical dystonia. It is composed of 24 items, forming 5 subscales: stigma, emotional well-being, pain, activities of daily living, and social/ family life. Items are rated on a 5-point scale. Each item consists of five statements representing increasing severity of impairment, scored from 0 to 4. Subjects will be instructed to indicate how they have felt during the past two weeks because of dystonia by selecting one of the five statements for each item. The total score reported here can range from 0-96, with a higher score indicating a greater impact of dystonia on quality of life.	absolute value at 12 Weeks