Back to resultsrTMS and Botulinum Toxin in Primary Cervical Dystonia
Primary Purpose
Primary Cervical Dystonia, Dystonia
Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
NeuroStar TMS therapy
Sham NeuroStar TMS therapy
Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS)
Craniocervical Dystonia Questionnaire (CDQ-24)
Cerebellar-brain Inhibition (CBI)
Botulinum toxin injections
Sponsored by
About this trial
This is an interventional treatment trial for Primary Cervical Dystonia focused on measuring Botulinum Toxin, Transcranial Magnetic Stimulation
Eligibility Criteria
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.
Sites / Locations
- UF Center for Movement Disorders & Neurorestoration
- UF Brain Institute
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Sham Comparator
Arm Label
Real rTMS Stimulation
Sham rTMS Stimulation
Arm Description
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.
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.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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 dividing the mean of amplitudes (mV) in response to conditioned stimulation by the mean of amplitudes (mV) in response to conditioned stimulation. 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.
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.
Full Information
NCT ID
NCT02542839
First Posted
June 23, 2015
Last Updated
August 22, 2023
Sponsor
University of Florida
Collaborators
American Brain Foundation, Neuronetics
1. Study Identification
Unique Protocol Identification Number
NCT02542839
Brief Title
rTMS and Botulinum Toxin in Primary Cervical Dystonia
Official Title
Combined Therapy With rTMS and Botulinum Toxin in Primary Cervical Dystonia
Study Type
Interventional
2. Study Status
Record Verification Date
August 2023
Overall Recruitment Status
Completed
Study Start Date
November 2015 (Actual)
Primary Completion Date
June 28, 2021 (Actual)
Study Completion Date
June 28, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Florida
Collaborators
American Brain Foundation, Neuronetics
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
Yes
Data Monitoring Committee
Yes
5. Study Description
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.
Detailed 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Primary Cervical Dystonia, Dystonia
Keywords
Botulinum Toxin, Transcranial Magnetic Stimulation
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderOutcomes Assessor
Allocation
Randomized
Enrollment
9 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Real rTMS Stimulation
Arm Type
Experimental
Arm Description
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.
Arm Title
Sham rTMS Stimulation
Arm Type
Sham Comparator
Arm Description
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.
Intervention Type
Device
Intervention Name(s)
NeuroStar TMS therapy
Intervention Description
Application of repetitious transcranial magnetic stimulation (TMS) pulses using NeuroStar device to a specific brain target at predefined stimulation parameters.
Intervention Type
Device
Intervention Name(s)
Sham NeuroStar TMS therapy
Intervention Description
Same procedure as real rTMS without stimulating the cerebral cortex.
Intervention Type
Other
Intervention Name(s)
Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS)
Intervention Description
All participants will receive a clinical assessment of dystonia severity by using the TWSTRS test.
Intervention Type
Other
Intervention Name(s)
Craniocervical Dystonia Questionnaire (CDQ-24)
Intervention Description
All participants will fill out the Craniocervical Dystonia Questionnaire (CDQ-24) quality of life questionnaire.
Intervention Type
Other
Intervention Name(s)
Cerebellar-brain Inhibition (CBI)
Intervention Description
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
Procedure
Intervention Name(s)
Botulinum toxin injections
Intervention Description
All participants will receive Botulinum toxin(BoNT) injections as part of their standard of care
Primary Outcome Measure Information:
Title
Dystonia Severity as Assessed by the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS)
Description
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.
Time Frame
absolute value at 12 weeks
Secondary Outcome Measure Information:
Title
TMS Measure Referred to as Cerebellar Inhibition (CBI)
Description
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 dividing the mean of amplitudes (mV) in response to conditioned stimulation by the mean of amplitudes (mV) in response to conditioned stimulation. 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.
Time Frame
absolute value at 12 weeks
Title
Craniocervical Dystonia Questionnaire
Description
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.
Time Frame
absolute value at 12 Weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
30 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Aparna Wagle-Shukla, M.D.
Organizational Affiliation
UF Center for Movement Disorders and Neurorestoration
Official's Role
Principal Investigator
Facility Information:
Facility Name
UF Center for Movement Disorders & Neurorestoration
City
Gainesville
State/Province
Florida
ZIP/Postal Code
32607
Country
United States
Facility Name
UF Brain Institute
City
Gainesville
State/Province
Florida
ZIP/Postal Code
32611
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
16928997
Citation
Tarsy D, Simon DK. Dystonia. N Engl J Med. 2006 Aug 24;355(8):818-29. doi: 10.1056/NEJMra055549. No abstract available.
Results Reference
background
PubMed Identifier
22030388
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.
Results Reference
background
PubMed Identifier
16987733
Citation
Jankovic J. Treatment of dystonia. Lancet Neurol. 2006 Oct;5(10):864-72. doi: 10.1016/S1474-4422(06)70574-9.
Results Reference
background
PubMed Identifier
25052566
Citation
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.
Results Reference
background
PubMed Identifier
24142590
Citation
Thenganatt MA, Jankovic J. Treatment of dystonia. Neurotherapeutics. 2014 Jan;11(1):139-52. doi: 10.1007/s13311-013-0231-4.
Results Reference
background
PubMed Identifier
17640522
Citation
Hallett M. Transcranial magnetic stimulation: a primer. Neuron. 2007 Jul 19;55(2):187-99. doi: 10.1016/j.neuron.2007.06.026.
Results Reference
background
PubMed Identifier
25034472
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.
Results Reference
background
PubMed Identifier
24771105
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.
Results Reference
background
PubMed Identifier
17188568
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.
Results Reference
background
Learn more about this trial
rTMS and Botulinum Toxin in Primary Cervical Dystonia
We'll reach out to this number within 24 hrs