rTMS and Botulinum Toxin in Primary Cervical Dystonia

December 5, 2023 updated by: University of Florida

Combined Therapy With rTMS and Botulinum Toxin in Primary Cervical Dystonia

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

9

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Florida
      • Gainesville, Florida, United States, 32607
        • UF Center for Movement Disorders & Neurorestoration
      • Gainesville, Florida, United States, 32611
        • UF Brain Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

30 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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.
Device: NeuroStar TMS therapy
Application of repetitious transcranial magnetic stimulation (TMS) pulses using NeuroStar device to a specific brain target at predefined stimulation parameters.
Other: Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS)
All participants will receive a clinical assessment of dystonia severity by using the TWSTRS test.
Other: Craniocervical Dystonia Questionnaire (CDQ-24)
All participants will fill out the Craniocervical Dystonia Questionnaire (CDQ-24) quality of life questionnaire.
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.
Procedure: Botulinum toxin injections
All participants will receive Botulinum toxin(BoNT) injections as part of their standard of care
Sham Comparator: 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.
Other: Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS)
All participants will receive a clinical assessment of dystonia severity by using the TWSTRS test.
Other: Craniocervical Dystonia Questionnaire (CDQ-24)
All participants will fill out the Craniocervical Dystonia Questionnaire (CDQ-24) quality of life questionnaire.
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.
Procedure: Botulinum toxin injections
All participants will receive Botulinum toxin(BoNT) injections as part of their standard of care
Device: Sham NeuroStar TMS therapy
Same procedure as real rTMS without stimulating the cerebral cortex.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Dystonia Severity as Assessed by the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS)
Time Frame: absolute value at 12 weeks
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Craniocervical Dystonia Questionnaire
Time Frame: absolute value at 12 Weeks
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
TMS Measure Referred to as Cerebellar Inhibition (CBI)
Time Frame: absolute value at 12 weeks
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Florida

Collaborators

American Brain Foundation
Neuronetics

Investigators

  • Principal Investigator: Aparna Wagle-Shukla, M.D., UF Center for Movement Disorders and Neurorestoration

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 1, 2015

Primary Completion (Actual)

June 28, 2021

Study Completion (Actual)

June 28, 2021

Study Registration Dates

First Submitted

June 23, 2015

First Submitted That Met QC Criteria

September 3, 2015

First Posted (Estimated)

September 7, 2015

Study Record Updates

Last Update Posted (Actual)

December 22, 2023

Last Update Submitted That Met QC Criteria

December 5, 2023

Last Verified

August 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IRB201500341

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

Yes

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Dystonia

Clinical Trials on NeuroStar TMS therapy

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Romania

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe