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rTMS and Botulinum Toxin in Primary Cervical Dystonia

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ClinicalTrials.gov Identifier: NCT02542839
Recruitment Status : Recruiting
First Posted : September 7, 2015
Last Update Posted : August 24, 2018
Sponsor:
Collaborators:
American Brain Foundation
Neuronetics
Information provided by (Responsible Party):
University of Florida

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.


Condition or disease Intervention/treatment Phase
Primary Cervical Dystonia Dystonia Device: NeuroStar TMS therapy 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 Not Applicable

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  (Clinical Trial)
Estimated Enrollment : 35 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Combined Therapy With rTMS and Botulinum Toxin in Primary Cervical Dystonia
Study Start Date : November 2015
Estimated Primary Completion Date : September 2019
Estimated Study Completion Date : September 2019


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.
Device: 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.

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




Primary Outcome Measures :
  1. Dystonia severity as assessed by the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) [ Time Frame: Baseline to 12 weeks ]
    A clinical assessment of dystonia severity will be conducted at each study visit using the TWSTRS. Videos will be taken of the subjects at baseline, 6 weeks, 10 weeks, and 12 week which will be scored by two independent blinded raters. The TWSTRS is a widely accepted composite rating scale for PCD with subscales for clinical severity, functional disability, and associated pain. Higher scores represent greater impairment and scores range from 0-87.


Secondary Outcome Measures :
  1. Physiological impact of TMS measured by Cerebellar Inhibition(CBI) [ Time Frame: Baseline to 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. The time course of effects on CBI will be measured at baseline, 6 weeks, and 12 weeks and determine if they correlate with clinical scoring of PCD symptoms.

  2. Quality of life as assessed by Craniocervical Dystonia Questionnaire [ Time Frame: Baseline to 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. Subjects will also rate their symptoms before and after stimulation using a 7-point nominal scale: 1) excellent, 2) very good, 3) good, 4) average, 5) slightly worse than usual, 6) bad or 7) very bad. Videos will be taken of the subjects at baseline, 6 weeks, 10 weeks, and 12 weeks which will be scored by two independent blinded raters.



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Ages Eligible for Study:   30 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02542839


Contacts
Contact: Aparna Wagle-Shukla, M.D. 352-294-5400 aparna.shukla@neurology.ufl.edu
Contact: Julie Segura, B.A. 352-294-5400 Julie.Segura@neurology.ufl.edu

Locations
United States, Florida
UF Center for Movement Disorders & Neurorestoration Recruiting
Gainesville, Florida, United States, 32607
Contact: Julie Segura, BA    352-273-5566    julie.segura@neurology.ufl.edu   
Contact: Wei Hu, MD         
Principal Investigator: Aparna Shukla, MD         
UF Brain Institute Recruiting
Gainesville, Florida, United States, 32611
Sponsors and Collaborators
University of Florida
American Brain Foundation
Neuronetics
Investigators
Principal Investigator: Aparna Wagle-Shukla, M.D. UF Center for Movement Disorders and Neurorestoration

Publications:

Responsible Party: University of Florida
ClinicalTrials.gov Identifier: NCT02542839     History of Changes
Other Study ID Numbers: IRB201500341
First Posted: September 7, 2015    Key Record Dates
Last Update Posted: August 24, 2018
Last Verified: August 2018

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
Device Product Not Approved or Cleared by U.S. FDA: No
Pediatric Postmarket Surveillance of a Device Product: No

Keywords provided by University of Florida:
Botulinum Toxin
Transcranial Magnetic Stimulation

Additional relevant MeSH terms:
Dystonia
Dystonic Disorders
Torticollis
Dyskinesias
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Movement Disorders
Central Nervous System Diseases
Botulinum Toxins
Acetylcholine Release Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Cholinergic Agents
Neurotransmitter Agents
Physiological Effects of Drugs