rTMS and Botulinum Toxin in Benign Essential Blepharospasm

Combined Effects of rTMS and Botulinum Toxin in Benign Essential Blepharospasm: A Novel Approach

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.

Study Overview

• Status: Completed
• Conditions: Benign Essential Blepharospasm
• Intervention / Treatment: Device: Magstim RapidStim2; Device: Sham Magstim RapidStim2

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.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Florida
    • Gainesville, Florida, United States, 32607
      • Center for Movement Disorders and Neurorestoration

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 28 years to 73 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Real rTMS stimulation; 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.	Device: Magstim RapidStim2; Application of repetitious transcranial magnetic stimulation (TMS) pulses using Magstim RapidStim2 to a specific brain target at predefined stimulation parameters.
Sham Comparator: Sham rTMS Stimulation; 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.	Device: Sham Magstim RapidStim2; Same procedure as real rTMS without stimulating the cerebral cortex.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	2 weeks after rTMS
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.	2 weeks after rTMS
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.	2 weeks after rTMS
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.	2 weeks after rTMS

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	2 weeks after rTMS
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.	2 weeks after rTMS
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.	2 weeks after rTMS

Collaborators and Investigators

• Sponsor: University of Florida
• Investigators: Principal Investigator: Aparna Wagle-Shukla, MD, University of Florida

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2015
• Primary Completion (Actual): May 1, 2017
• Study Completion (Actual): November 1, 2017

Study Registration Dates

• First Submitted: February 10, 2015
• First Submitted That Met QC Criteria: February 24, 2015
• First Posted (Estimated): February 25, 2015

Study Record Updates

• Last Update Posted (Actual): September 15, 2023
• Last Update Submitted That Met QC Criteria: September 12, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Eye Diseases; Eyelid Diseases; Blepharospasm
• Other Study ID Numbers: 201400993

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes