Back to resultsrTMS and Botulinum Toxin in Benign Essential Blepharospasm
Primary Purpose
Benign Essential Blepharospasm
Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Magstim RapidStim2
Sham Magstim RapidStim2
Sponsored by
About this trial
This is an interventional treatment trial for Benign Essential Blepharospasm
Eligibility Criteria
Inclusion Criteria:
- subjects diagnosed with blepharospasm or cranio-cervical dystonia who receive BoNT therapy at the Center for Movement Disorders will be approached. The investigators will enroll only those subjects who report experiencing positive benefits with BoNT but lasting about 10 weeks or less.
Exclusion Criteria:
- pregnancy
- active seizure disorder
- significant cognitive impairment
- exposure to neuroleptics
- presence of a metallic body such as pacemaker, implants, prosthesis, artificial limb or joint, shunt, metal rods and hearing aid.
Sites / Locations
- Center for Movement Disorders and Neurorestoration
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Sham Comparator
Arm Label
Real rTMS stimulation
Sham rTMS Stimulation
Arm Description
Repetitious transcranial magnetic stimulation (rTMS) will be delivered using the Magstim RapidStim2 over each anterior cingulate cortex, using a figure-of-eight coil. The investigators will apply rTMS with 0.2 Hz frequency to the ACC. 180 stimuli will be delivered with a stimulator output of 100% active motor threshold (AMT). AMT will be assessed at the tibialis anterior muscle with the coil. The AMT will be defined as the lowest stimulation intensity required to evoke a 150 μV potential in the target muscle. To determine the stimulation site for ACC, the coil will be placed over Fz and then moved over the midline of the brain in 0.5-cm steps anteriorly, until the point of maximum motor evoked potential in the orbicularis oculi (OO) muscle. The coil position will be marked on the skin. These rTMS sessions will be repeated daily for 10 days.
During sham repetitious transcranial magnetic stimulation (rTMS), subjects will undergo the same procedure for identifying stimulus location as used in patients receiving real rTMS using the sham Magstim RapidStim2 coil. This coil will be placed on the patient's head in an identical manner however will not be connected to the Magstim device. Instead another coil will be connected to provide stimulation sound. In each stimulation condition, the Magstim will be placed behind the patient and not visible to him or her. Placebo sham coil which produces discharge noise and vibration similar to a real coil without stimulating the cerebral cortex. During rTMS, all patients will continue to wear ear plugs as instructed during the real stimulation sessions.
Outcomes
Primary Outcome Measures
Change in JRS Severity Score
The change in the score of the Jankovic Rating Scale subscore for severity. Rated on a 5-point scale (0-4), where a higher score indicates higher severity of blepharospasm.
Change in JRS Frequency Score
The change in the score of the Jankovic Rating Scale subscore for frequency. Rated on a 5-point scale (0-4), where a higher score indicates higher frequency of forced blinks in blepharospasm.
Change in Number of Sustained Forced Eye Blinks
A video recording (5 minutes) was scored by two blinded neurologists to count the number of sustained forced eye-blinks.
Change in Duration of Forced Blinks
A video recording (5 minutes) was scored by two blinded neurologists to count the duration of sustained forced eye-blinks.
Secondary Outcome Measures
Change in CDQ-24 QOL Score
Change in score of the Craniocervical dystonia questionnaire (CDQ-24), a self-reported questionnaire designed to evaluate the impact of dystonia on activities of daily living and quality of life. The total CDQ-24 score can therefore range from 0 to 96, with higher scores meaning greater impairment due to dystonia.
Change in CDQ-24 ADL Subscore
Change in Actitivities of Daily Living (ADL) subscore of the Craniocervical dystonia questionnaire (CDQ-24), a questionnaire designed to evaluate quality of life outcomes for patients with dystonia. The ADL subscore is obtained from 6 of the 24 questions. Each question is rated on a 5-point scale (0-4), where a higher number indicates increasing severity of impairment for that daily activity due to dystonia. The total ADL subscore takes the sum of the number from five questions (a value from 0 to 24), then linearly transforms that sum to a 0-100 scale, where a higher score means greater impairment in daily life.
Change in Social Subscale of CDQ-24
Change in the social subscore of the Craniocervical dystonia questionnaire (CDQ-24), a questionnaire designed to evaluate quality of life outcomes for patients with dystonia. The social subscore is obtained from 4 of the 24 questions. Each question is rated on a 5-point scale (0-4), where a higher number indicates increasing severity of social impairment due to dystonia. The total social subscore can therefore range from 0 to 16, with higher scores meaning greater impairment of social activities.
Full Information
NCT ID
NCT02370875
First Posted
February 10, 2015
Last Updated
September 12, 2023
Sponsor
University of Florida
1. Study Identification
Unique Protocol Identification Number
NCT02370875
Brief Title
rTMS and Botulinum Toxin in Benign Essential Blepharospasm
Official Title
Combined Effects of rTMS and Botulinum Toxin in Benign Essential Blepharospasm: A Novel Approach
Study Type
Interventional
2. Study Status
Record Verification Date
September 2023
Overall Recruitment Status
Completed
Study Start Date
February 2015 (Actual)
Primary Completion Date
May 2017 (Actual)
Study Completion Date
November 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Florida
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
Benign essential blepharospasm (BEB) is a functionally disabling focal dystonia. Botulinum neurotoxin (BoNT) therapy is suboptimal in many BEB patients. Repetitious transcranial magnetic stimulation (rTMS) therapy is a promising noninvasive therapy and has shown positive benefits in BEB. rTMS therapy can be easily combined with BoNT injections to enhance the effects of BoNT in BEB.
Detailed Description
A two week course of rTMS therapy to achieve sustained benefits will be employed. With standard BoNT treatment, the peak-dose benefits are seen at about 4-6 weeks after the administration of injections. rTMS will be introduced during this peak-dose period (about 6 weeks after BoNT or T1).The effects of combined therapy at about 10 weeks after BoNT injections (T2) and at about 12 weeks after BoNT injections (T3) will be examined along with the physiological effects at these time points.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Benign Essential Blepharospasm
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderOutcomes Assessor
Allocation
Randomized
Enrollment
12 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Real rTMS stimulation
Arm Type
Experimental
Arm Description
Repetitious transcranial magnetic stimulation (rTMS) will be delivered using the Magstim RapidStim2 over each anterior cingulate cortex, using a figure-of-eight coil. The investigators will apply rTMS with 0.2 Hz frequency to the ACC. 180 stimuli will be delivered with a stimulator output of 100% active motor threshold (AMT). AMT will be assessed at the tibialis anterior muscle with the coil. The AMT will be defined as the lowest stimulation intensity required to evoke a 150 μV potential in the target muscle. To determine the stimulation site for ACC, the coil will be placed over Fz and then moved over the midline of the brain in 0.5-cm steps anteriorly, until the point of maximum motor evoked potential in the orbicularis oculi (OO) muscle. The coil position will be marked on the skin. These rTMS sessions will be repeated daily for 10 days.
Arm Title
Sham rTMS Stimulation
Arm Type
Sham Comparator
Arm Description
During sham repetitious transcranial magnetic stimulation (rTMS), subjects will undergo the same procedure for identifying stimulus location as used in patients receiving real rTMS using the sham Magstim RapidStim2 coil. This coil will be placed on the patient's head in an identical manner however will not be connected to the Magstim device. Instead another coil will be connected to provide stimulation sound. In each stimulation condition, the Magstim will be placed behind the patient and not visible to him or her. Placebo sham coil which produces discharge noise and vibration similar to a real coil without stimulating the cerebral cortex. During rTMS, all patients will continue to wear ear plugs as instructed during the real stimulation sessions.
Intervention Type
Device
Intervention Name(s)
Magstim RapidStim2
Intervention Description
Application of repetitious transcranial magnetic stimulation (TMS) pulses using Magstim RapidStim2 to a specific brain target at predefined stimulation parameters.
Intervention Type
Device
Intervention Name(s)
Sham Magstim RapidStim2
Intervention Description
Same procedure as real rTMS without stimulating the cerebral cortex.
Primary Outcome Measure Information:
Title
Change in JRS Severity Score
Description
The change in the score of the Jankovic Rating Scale subscore for severity. Rated on a 5-point scale (0-4), where a higher score indicates higher severity of blepharospasm.
Time Frame
2 weeks after rTMS
Title
Change in JRS Frequency Score
Description
The change in the score of the Jankovic Rating Scale subscore for frequency. Rated on a 5-point scale (0-4), where a higher score indicates higher frequency of forced blinks in blepharospasm.
Time Frame
2 weeks after rTMS
Title
Change in Number of Sustained Forced Eye Blinks
Description
A video recording (5 minutes) was scored by two blinded neurologists to count the number of sustained forced eye-blinks.
Time Frame
2 weeks after rTMS
Title
Change in Duration of Forced Blinks
Description
A video recording (5 minutes) was scored by two blinded neurologists to count the duration of sustained forced eye-blinks.
Time Frame
2 weeks after rTMS
Secondary Outcome Measure Information:
Title
Change in CDQ-24 QOL Score
Description
Change in score of the Craniocervical dystonia questionnaire (CDQ-24), a self-reported questionnaire designed to evaluate the impact of dystonia on activities of daily living and quality of life. The total CDQ-24 score can therefore range from 0 to 96, with higher scores meaning greater impairment due to dystonia.
Time Frame
2 weeks after rTMS
Title
Change in CDQ-24 ADL Subscore
Description
Change in Actitivities of Daily Living (ADL) subscore of the Craniocervical dystonia questionnaire (CDQ-24), a questionnaire designed to evaluate quality of life outcomes for patients with dystonia. The ADL subscore is obtained from 6 of the 24 questions. Each question is rated on a 5-point scale (0-4), where a higher number indicates increasing severity of impairment for that daily activity due to dystonia. The total ADL subscore takes the sum of the number from five questions (a value from 0 to 24), then linearly transforms that sum to a 0-100 scale, where a higher score means greater impairment in daily life.
Time Frame
2 weeks after rTMS
Title
Change in Social Subscale of CDQ-24
Description
Change in the social subscore of the Craniocervical dystonia questionnaire (CDQ-24), a questionnaire designed to evaluate quality of life outcomes for patients with dystonia. The social subscore is obtained from 4 of the 24 questions. Each question is rated on a 5-point scale (0-4), where a higher number indicates increasing severity of social impairment due to dystonia. The total social subscore can therefore range from 0 to 16, with higher scores meaning greater impairment of social activities.
Time Frame
2 weeks after rTMS
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:
subjects diagnosed with blepharospasm or cranio-cervical dystonia who receive BoNT therapy at the Center for Movement Disorders will be approached. The investigators will enroll only those subjects who report experiencing positive benefits with BoNT but lasting about 10 weeks or less.
Exclusion Criteria:
pregnancy
active seizure disorder
significant cognitive impairment
exposure to neuroleptics
presence of a metallic body such as pacemaker, implants, prosthesis, artificial limb or joint, shunt, metal rods and hearing aid.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Aparna Wagle-Shukla, MD
Organizational Affiliation
University of Florida
Official's Role
Principal Investigator
Facility Information:
Facility Name
Center for Movement Disorders and Neurorestoration
City
Gainesville
State/Province
Florida
ZIP/Postal Code
32607
Country
United States
12. IPD Sharing Statement
Learn more about this trial
rTMS and Botulinum Toxin in Benign Essential Blepharospasm
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