Benign Essential BlepharospasmNCT02370875
rTMS and Botulinum Toxin in Benign Essential Blepharospasm
A study testing Magstim RapidStim2 in people with Benign Essential Blepharospasm, run by University of Florida at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 30 to 75 years
- Conditions the study is for
- Benign Essential Blepharospasm
- What is being tested?
- Magstim RapidStim2
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 12 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2015to Nov 2017
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 30 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Center for Movement Disorders and Neurorestoration
Gainesville, Florida, 32607
About this study
Official title: 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.
Read the 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.
- Conditions
- Benign Essential Blepharospasm
- Being tested
- Magstim RapidStim2, Sham Magstim RapidStim2
- Medical subject headings
- Benign essential blepharospasm
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Magstim RapidStim2Device
Application of repetitious transcranial magnetic stimulation (TMS) pulses using Magstim RapidStim2 to a specific brain target at predefined stimulation parameters.
Sham Magstim RapidStim2Device
Same procedure as real rTMS without stimulating the cerebral cortex.
| Study group | Role | What they receive |
|---|---|---|
| Real rTMS stimulation | Experimental | 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. Receives: Device: Magstim RapidStim2 |
| Sham rTMS Stimulation | Sham comparator | 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. Receives: Device: Sham Magstim RapidStim2 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 2 weeks after rTMS
Secondary outcomes (3)
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.
Measured: 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.
Measured: 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.
Measured: 2 weeks after rTMS
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Feb 2015 (estimated)
- Study startFeb 2015
- Primary completionMay 2017
- Study completionNov 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Benign Essential BlepharospasmStudies of the same condition, open and under way.
- More trials run by University of FloridaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Outcomes assessor
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Florida
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Aparna Wagle-Shukla, MD, Principal investigator, University of Florida
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02370875
- Sponsor's protocol ID
- 201400993
- Status last verified
- Sep 2023
- First submitted
- 10 Feb 2015
- Last updated
- 15 Sep 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 15 Sep 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Combined Effects of rTMS and Botulinum Toxin in Benign Essential Blepharospasm: A Novel Approach
- ClinicalTrials.gov ID
- NCT02370875
- Acronym / sponsor ID
- 201400993
- Conditions
- Benign Essential Blepharospasm
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- University of FloridaUniversity, hospital or other
- Study start
- Feb 2015 (actual)
- Primary completion
- May 2017 (actual)
- Study completion
- Nov 2017 (actual)
- First posted
- 25 Feb 2015 (estimated)
- Results
- Posted 15 Sep 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Real rTMS stimulation | Experimental | Device: Magstim RapidStim2Repetitious 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. |
| Sham rTMS Stimulation | Sham comparator | Device: Sham Magstim RapidStim2During 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. |
Who may qualify
- Ages
- 30 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- 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.
Key exclusion criteria (5 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Magstim RapidStim2Application of repetitious transcranial magnetic stimulation (TMS) pulses using Magstim RapidStim2 to a specific brain target at predefined stimulation parameters. | Device | Real rTMS stimulation |
| Sham Magstim RapidStim2Same procedure as real rTMS without stimulating the cerebral cortex. | Device | Sham rTMS Stimulation |
Primary outcome
Change in JRS Severity Score
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 2 weeks after rTMS
A video recording (5 minutes) was scored by two blinded neurologists to count the duration of sustained forced eye-blinks.
3 secondary outcomes
Change in CDQ-24 QOL Score
Time frame: 2 weeks after rTMS
Change in CDQ-24 ADL Subscore
Time frame: 2 weeks after rTMS
Change in Social Subscale of CDQ-24
Time frame: 2 weeks after rTMS
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Sep 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Effects of DaxibotulinumtoxinA for Blepharospasm and Hemifacial Spasm
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Aparna Wagle-Shukla, MD principal investigator
University of Florida
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Magstim RapidStim2 in people with Benign Essential Blepharospasm, run by University of Florida at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 15 Sep 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in JRS Severity Score (time frame: 2 weeks after rTMS). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Sep 2023.