rTMS and Botulinum Toxin in Benign Essential Blepharospasm

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

Status

Completed

Phases

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02370875

Enrollment

Registered

2015-02-25

Start date

2015-02-28

Completion date

2017-11-30

Last updated

2023-09-15

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Benign Essential Blepharospasm

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.

Interventions

DEVICEMagstim RapidStim2

Application of repetitious transcranial magnetic stimulation (TMS) pulses using Magstim RapidStim2 to a specific brain target at predefined stimulation parameters.

DEVICESham Magstim RapidStim2

Same procedure as real rTMS without stimulating the cerebral cortex.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

TRIPLE (Subject, Caregiver, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

30 Years to 75 Years

Healthy volunteers

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.

Design outcomes

Primary

Measure	Time frame	Description
Change in JRS Severity Score	2 weeks after rTMS	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	2 weeks after rTMS	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	2 weeks after rTMS	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	2 weeks after rTMS	A video recording (5 minutes) was scored by two blinded neurologists to count the duration of sustained forced eye-blinks.

Secondary

Measure	Time frame	Description
Change in CDQ-24 ADL Subscore	2 weeks after rTMS	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	2 weeks after rTMS	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.
Change in CDQ-24 QOL Score	2 weeks after rTMS	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.

Countries

United States

Participant flow

Participants by arm

Arm	Count
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. Magstim RapidStim2: Application of repetitious transcranial magnetic stimulation (TMS) pulses using Magstim RapidStim2 to a specific brain target at predefined stimulation parameters.	6
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. Magstim RapidStim2: Application of repetitious transcranial magnetic stimulation (TMS) pulses using Magstim RapidStim2 to a specific brain target at predefined stimulation parameters.	6
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. Sham Magstim RapidStim2: Same procedure as real rTMS without stimulating the cerebral cortex.	6
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. Sham Magstim RapidStim2: Same procedure as real rTMS without stimulating the cerebral cortex.	6
Total	24

Baseline characteristics

Characteristic	Real rTMS Stimulation	Sham rTMS Stimulation	Total
Age, Categorical <=18 years	0 Participants	0 Participants	0 Participants
Age, Categorical >=65 years	2 Participants	2 Participants	4 Participants
Age, Categorical Between 18 and 65 years	4 Participants	4 Participants	8 Participants
Age, Continuous	68.8 Years STANDARD_DEVIATION 7.4	69.3 Years STANDARD_DEVIATION 7.2	69.1 Years STANDARD_DEVIATION 7.1
BEB blink frequency on video rating	38.7 Blinks per minute STANDARD_DEVIATION 15.2	37 Blinks per minute STANDARD_DEVIATION 16.7	37.9 Blinks per minute STANDARD_DEVIATION 9.2
BEB frequency on Jankovic Rating Scale	3.3 Score on evaluation STANDARD_DEVIATION 0.7	2.6 Score on evaluation STANDARD_DEVIATION 1.2	2.9 Score on evaluation STANDARD_DEVIATION 0.8
BEB severity on Jankovic Rating Scale	3.1 Score on evaluation STANDARD_DEVIATION 0.1	2.5 Score on evaluation STANDARD_DEVIATION 1.1	2.8 Score on evaluation STANDARD_DEVIATION 0.5
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Black or African American	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) White	6 Participants	6 Participants	12 Participants
Region of Enrollment United States	6 participants	6 participants	12 participants
Sex: Female, Male Female	4 Participants	5 Participants	9 Participants
Sex: Female, Male Male	2 Participants	1 Participants	3 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 6	0 / 6
other Total, other adverse events	0 / 6	0 / 6
serious Total, serious adverse events	0 / 6	0 / 6

Outcome results

Primary

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.