rTMS and Botulinum Toxin in Primary Cervical Dystonia

NCT02542839 | Completed Results DMC FDA Device

• 1 other identifier: IRB201500341
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Primary Cervical Dystonia; Dystonia

Keywords

Botulinum Toxin; Transcranial Magnetic Stimulation

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• TMS Measure Referred to as Cerebellar Inhibition (CBI)

  absolute value at 12 weeks

• Craniocervical Dystonia Questionnaire

  absolute value at 12 Weeks

Study Arms (2)

Real rTMS Stimulation

EXPERIMENTAL

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.

Device: NeuroStar TMS therapy; Other: Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS); Other: Craniocervical Dystonia Questionnaire (CDQ-24); Other: Cerebellar-brain Inhibition (CBI); Procedure: Botulinum toxin injections

Sham rTMS Stimulation

SHAM COMPARATOR

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.

Device: Sham NeuroStar TMS therapy; Other: Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS); Other: Craniocervical Dystonia Questionnaire (CDQ-24); Other: Cerebellar-brain Inhibition (CBI); Procedure: Botulinum toxin injections

Interventions

NeuroStar TMS therapy DEVICE

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

Real rTMS Stimulation

Sham NeuroStar TMS therapy DEVICE

Same procedure as real rTMS without stimulating the cerebral cortex.

Sham rTMS Stimulation

Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) OTHER

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

Real rTMS Stimulation; Sham rTMS Stimulation

Craniocervical Dystonia Questionnaire (CDQ-24) OTHER

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

Real rTMS Stimulation; Sham rTMS Stimulation

Cerebellar-brain Inhibition (CBI) 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.

Real rTMS Stimulation; Sham rTMS Stimulation

Botulinum toxin injections PROCEDURE

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

Real rTMS Stimulation; Sham rTMS Stimulation

Eligibility Criteria

• Age: 30 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

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

Sponsors & Collaborators

• University of Florida: lead
• American Brain Foundation: collaborator
• Neuronetics: collaborator

Study Sites (2)

UF Center for Movement Disorders & Neurorestoration

Gainesville, Florida, 32607, United States

Location

UF Brain Institute

Gainesville, Florida, 32611, United States

Location

Related Publications (9)

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

  PMID: 16928997 BACKGROUND

• 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.

  PMID: 22030388 BACKGROUND

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

  PMID: 16987733 BACKGROUND

• 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.

  PMID: 25052566 BACKGROUND

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

  PMID: 24142590 BACKGROUND

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

  PMID: 17640522 BACKGROUND

• 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.

  PMID: 25034472 BACKGROUND

• 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.

  PMID: 24771105 BACKGROUND

• 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.

  PMID: 17188568 BACKGROUND

MeSH Terms

Conditions

Cervical Dystonia, Primary; Dystonia

Condition Hierarchy (Ancestors)

Dyskinesias; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Aparna Wagle Shukla
• Organization: University of Florida

aparna.shukla@neurology.ufl.edu

3522945400

Study Officials

• Aparna Wagle-Shukla, M.D.

  UF Center for Movement Disorders and Neurorestoration

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 23, 2015
• First Posted: September 7, 2015
• Study Start: November 1, 2015
• Primary Completion: June 28, 2021
• Study Completion: June 28, 2021
• Last Updated: December 22, 2023
• Results First Posted: September 15, 2023

Record last verified: 2023-08

Locations

US (2)