Trial Outcomes & Findings for rTMS and Botulinum Toxin in Benign Essential Blepharospasm (NCT NCT02370875)
NCT ID: NCT02370875
Last Updated: 2023-09-15
Results Overview
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.
Recruitment status
COMPLETED
Study phase
NA
Target enrollment
12 participants
Primary outcome timeframe
2 weeks after rTMS
Results posted on
2023-09-15
Participant Flow
Unit of analysis: sets of eyes
Participant milestones
| Measure |
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.
|
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.
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|---|---|---|
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Overall Study
STARTED
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6 6
|
6 6
|
|
Overall Study
COMPLETED
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6 6
|
6 6
|
|
Overall Study
NOT COMPLETED
|
0 0
|
0 0
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Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
rTMS and Botulinum Toxin in Benign Essential Blepharospasm
Baseline characteristics by cohort
| Measure |
Real rTMS Stimulation
n=6 sets of eyes
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.
|
Sham rTMS Stimulation
n=6 sets of eyes
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.
|
Total
n=12 sets of eyes
Total of all reporting groups
|
|---|---|---|---|
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Age, Categorical
<=18 years
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
4 Participants
n=93 Participants
|
4 Participants
n=4 Participants
|
8 Participants
n=27 Participants
|
|
Age, Categorical
>=65 years
|
2 Participants
n=93 Participants
|
2 Participants
n=4 Participants
|
4 Participants
n=27 Participants
|
|
Age, Continuous
|
68.8 Years
STANDARD_DEVIATION 7.4 • n=93 Participants
|
69.3 Years
STANDARD_DEVIATION 7.2 • n=4 Participants
|
69.1 Years
STANDARD_DEVIATION 7.1 • n=27 Participants
|
|
Sex: Female, Male
Female
|
4 Participants
n=93 Participants
|
5 Participants
n=4 Participants
|
9 Participants
n=27 Participants
|
|
Sex: Female, Male
Male
|
2 Participants
n=93 Participants
|
1 Participants
n=4 Participants
|
3 Participants
n=27 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
White
|
6 Participants
n=93 Participants
|
6 Participants
n=4 Participants
|
12 Participants
n=27 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Region of Enrollment
United States
|
6 participants
n=93 Participants
|
6 participants
n=4 Participants
|
12 participants
n=27 Participants
|
|
BEB severity on Jankovic Rating Scale
|
3.1 Score on evaluation
STANDARD_DEVIATION 0.1 • n=6 sets of eyes
|
2.5 Score on evaluation
STANDARD_DEVIATION 1.1 • n=6 sets of eyes
|
2.8 Score on evaluation
STANDARD_DEVIATION 0.5 • n=12 sets of eyes
|
|
BEB frequency on Jankovic Rating Scale
|
3.3 Score on evaluation
STANDARD_DEVIATION 0.7 • n=6 sets of eyes
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2.6 Score on evaluation
STANDARD_DEVIATION 1.2 • n=6 sets of eyes
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2.9 Score on evaluation
STANDARD_DEVIATION 0.8 • n=12 sets of eyes
|
|
BEB blink frequency on video rating
|
38.7 Blinks per minute
STANDARD_DEVIATION 15.2 • n=6 sets of eyes
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37 Blinks per minute
STANDARD_DEVIATION 16.7 • n=6 sets of eyes
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37.9 Blinks per minute
STANDARD_DEVIATION 9.2 • n=12 sets of eyes
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PRIMARY outcome
Timeframe: 2 weeks after rTMSThe 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.
Outcome measures
| Measure |
Real rTMS Stimulation
n=6 sets of eyes
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.
|
Sham rTMS Stimulation
n=6 sets of eyes
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.
|
|---|---|---|
|
Change in JRS Severity Score
|
-1.8 Change in score
Standard Deviation 0.8
|
-0.1 Change in score
Standard Deviation 0.23
|
PRIMARY outcome
Timeframe: 2 weeks after rTMSThe 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.
Outcome measures
| Measure |
Real rTMS Stimulation
n=6 sets of eyes
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.
|
Sham rTMS Stimulation
n=6 sets of eyes
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.
|
|---|---|---|
|
Change in JRS Frequency Score
|
-1.4 Change in score
Standard Deviation 0.8
|
-0.1 Change in score
Standard Deviation 0.2
|
PRIMARY outcome
Timeframe: 2 weeks after rTMSA video recording (5 minutes) was scored by two blinded neurologists to count the number of sustained forced eye-blinks.
Outcome measures
| Measure |
Real rTMS Stimulation
n=6 sets of eyes
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.
|
Sham rTMS Stimulation
n=6 sets of eyes
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.
|
|---|---|---|
|
Change in Number of Sustained Forced Eye Blinks
|
-2.3 blinks per 5 minutes
Standard Deviation 0.8
|
-0.5 blinks per 5 minutes
Standard Deviation 0.1
|
PRIMARY outcome
Timeframe: 2 weeks after rTMSA video recording (5 minutes) was scored by two blinded neurologists to count the duration of sustained forced eye-blinks.
Outcome measures
| Measure |
Real rTMS Stimulation
n=6 sets of eyes
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.
|
Sham rTMS Stimulation
n=6 sets of eyes
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.
|
|---|---|---|
|
Change in Duration of Forced Blinks
|
-2.6 Change in seconds
Standard Deviation 1.1
|
-0.3 Change in seconds
Standard Deviation 0.8
|
SECONDARY outcome
Timeframe: 2 weeks after rTMSPopulation: Score from self-reported questionnaire
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.
Outcome measures
| Measure |
Real rTMS Stimulation
n=6 Participants
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.
|
Sham rTMS Stimulation
n=6 Participants
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.
|
|---|---|---|
|
Change in CDQ-24 QOL Score
|
-10.6 Change in score
Standard Deviation 5.1
|
-4.3 Change in score
Standard Deviation 2.1
|
SECONDARY outcome
Timeframe: 2 weeks after rTMSChange 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.
Outcome measures
| Measure |
Real rTMS Stimulation
n=6 Participants
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.
|
Sham rTMS Stimulation
n=6 Participants
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.
|
|---|---|---|
|
Change in CDQ-24 ADL Subscore
|
-30 Change in score
Standard Deviation 12.1
|
-15 Change in score
Standard Deviation 13.2
|
SECONDARY outcome
Timeframe: 2 weeks after rTMSChange 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.
Outcome measures
| Measure |
Real rTMS Stimulation
n=6 Participants
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.
|
Sham rTMS Stimulation
n=6 Participants
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.
|
|---|---|---|
|
Change in Social Subscale of CDQ-24
|
-15 Change in score
Standard Deviation 11.2
|
-2.5 Change in score
Standard Deviation 13.2
|
Adverse Events
Real rTMS Stimulation
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Sham rTMS Stimulation
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
Adverse event data not reported
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place