BlepharospasmPhase 2NCT00411255
Brain Stimulation to Treat Blepharospasm or Meige Syndrome
A Phase 2 study testing repetitive transcranial magnetic stimulation (rTMS) in people with Blepharospasm and Focal Dystonia, run by National Institute of Neurological Disorders and Stroke (NINDS) at 1 site in United States.
Trial summary
This research study will examine whether magnetic or electrical stimulation of the brain can improve the involuntary closure of the eyelids in patients with blepharospasm or Meige syndrome; conditions that belong to a group of neurological disorders called dystonias. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Blepharospasm, Focal Dystonia
- What is being tested?
- repetitive transcranial magnetic stimulation (rTMS)
- Type of treatment
- Surgery or procedure
- How many people
- 22 participants
- Where
- 1 siteUnited States
- Study dates
- 22 Jun 2006to 7 Apr 2009
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with idiopathic BSP or Meige-Syndrome (=BSP plus oromandibular dystonia).
- Age 18 years or older.
- Normal findings in the medical history, physical and neurological examination, except for dystonia (in cases that patients have not had an H\& P at the NIH within the last 12 months; they will undergo all these exams on the first study day).
- Last treatment with botulinum toxin more than three months ago.
- Age 18 years or older
- Normal findings in the medical history, physical and neurological examination
- No history of neuroleptic medications/ prior use of neuroleptics (such as Haldol(Registered Trademark))
- Not been treated or taken anti-depressants, anti-seizure medication, anticholinergic drugs (such as Artane(Registered Trademark)) and muscle relaxants within the past 4 weeks
Who cannot join
- Any of the following will exclude a patient from the study:
- Other disease with involuntary blinking (Hemifacial spasm, Tic disorder, Tardive Dyskinesia, Tardive dystonia, etc).
- BSP and normal recovery of R2 in BRR.
- Participation in a clinical trial in the 2 weeks preceding the study.
- History of seizure disorder.
- Pregnancy- a pregnancy test will be performed for women of childbearing potential.
Show all 13Show fewer
- Symptoms of a clinically relevant illness in the 4 weeks before the first study day, including history of any other neurological disorders or conditions requiring the use of anti-depressants, neuroleptic medications or anti-seizure meds., anticholinergic drugs and muscle relaxants.
- History of neuroleptic medications/prior use of neuroleptics.
- A botulinum toxin injection within 3 months of starting the protocol
- Any condition that requires the use of anti-depressants, anti-psychotic or anti-seizure medications
- Cannot follow the instruction through the entire recording
- Not able to provide consent to participate in the study
- Patients will be screened and recruited from the outpatient clinic of the HMCS, NINDS. Age matched volunteers will be recruited from the NIH Patient Recruitment and Public Liaison Office.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institute of Neurological Disorders and Stroke (NINDS), 9000 Rockville
Bethesda, Maryland, 20892
About this study
Official title: Blepharospasm and the Experimental Modulation of Cortical Excitability in Primary and Secondary Motor Areas. A Pilot Study.
This research study will examine whether magnetic or electrical stimulation of the brain can improve the involuntary closure of the eyelids in patients with blepharospasm or Meige syndrome; conditions that belong to a group of neurological disorders called dystonias. Blepharospasm and Meige syndrome cause excessive involuntary closure of the eyelids or blinking. In an earlier study of patients with writer's cramp, which is another form of dystonia, symptoms improved temporarily with brain stimulation.
Interested people 18 years of age or older with blepharospasm or Meige syndrome may be eligible for this study. Candidates are screened with a medical history, physical examination and a blink reflex test.
Read more
Participants undergo brain stimulation and evaluations before and after the stimulation to test the response, as follows:
Procedures
- Transcranial magnetic stimulation (TMS): A wire coil is held on the patient's scalp. A brief electrical current is passed through the coil, creating a magnetic pulse that stimulates the brain. The subject hears a click and may feel a pulling sensation on the skin under the coil. There may be a twitch in the muscles of the face, arm or leg. The subject may be asked to tense certain muscles slightly or perform other simple actions. The effect of TMS on the muscles is detected with small metal disk electrodes taped to the skin of the arms or legs. TMS is done on eight of the ten test days.
- Repetitive TMS (rTMS): The same procedure as TMS, except repeated magnetic pulses are delivered in short bursts. RTMS is done on eight of the ten test days.
- Theta burst stimulation (TBS): A form of rTMS that involves short bursts of impulses. TBS is done on four study days.
- Cathodal transcranial DC stimulation (tDCS): Two conductive-rubber electrodes placed in saline-soaked sponges are positioned over two areas of the head. A constant weak electrical current flow is applied for 20 minutes. tDCS is done on two study days.
Evaluations
- Physician observation: The subject's eyes are videotaped for 5 minutes before and after each TMS session. A physician then counts how many times the subject blinked during the 5 minutes.
- Questionnaire: Subjects are asked to rate their symptoms before and after brain stimulation.
- Electrophysiological test of the blink reflex: Wires are taped to the skin on the nose and temple to record the eye movement during blinking. A thin plastic rod is placed on the skin over the right e...
Read the detailed description
BACKGROUND: Blepharospasm (BSP) is a common form of focal dystonia, but the etiology and underlying pathophysiological mechanisms are still obscure. BSP is characterized by excessive involuntary closure of the eyelids. Pathological changes in excitability in the primary motor cortex (MC) and secondary motor areas, such as the anterior cingulate (AC), pre-and supplementary cortex (PMC, SMA) are suggested from electrophysiological and brain imaging studies. It is conceivable that modulation of excitability in some of these areas may lead to amelioration of the symptoms of BSP. Cortical excitability can be experimentally changed by various well-established electrophysiological techniques non-invasively.
METHODS: In this pilot protocol, studying 30 patients with BSP, we will use repetitive transcranial magnetic stimulation (rTMS) over the AC, PMC, SMA and MC in two different inhibitory modes: low frequency rTMS ((lf) rTMS) and continuous theta burst stimulation cTBS. Furthermore, we will apply transcranial direct stimulation (tDCS) in an inhibitory mode (cathodal tDCS) over the MC and low intensity high frequency supraorbital electrical stimulation; the latter will be performed in patients and in 7 healthy subjects. The effects on blepharospasm will be objectively measured by electrophysiological measures (blink reflex recovery curve (BRR), blink rate observation by an investigator blinded to the intervention, and a subjective rating by the patient.
OBJECTIVES: We hypothesize that we will find variable amounts of clinical improvement in BSP patients with these different methods. With this study, we aim to get more insight to the underlying pathophysiological mechanisms of BSP and identify which method of non-invasive brain stimulation may be clinically most efficacious.
- Conditions
- Blepharospasm, Focal Dystonia
- Being tested
- repetitive transcranial magnetic stimulation (rTMS)
- Keywords
- Blink Reflex, Transcranial Magnetic Stimulation (TMS), Dystonia, Blepharospasm, BSP, Focal Dystonia
- Medical subject headings
- Blepharospasm, Dystonic Disorders, Dystonia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
repetitive transcranial magnetic stimulation (rTMS)Procedure or surgery
Three arms on three different days 180 stimuli will be delivered to the AC with a sham coil, with the H-coil and with a standard circular coil in separate sessions.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Dec 2006 (estimated)
- Study start22 Jun 2006
- Primary completion7 Apr 2009
- Study completion7 Apr 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for BlepharospasmStudies of the same condition, open and under way.
- More trials run by National Institute of Neurological Disorders and Stroke (NINDS)The 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 2
- Primary purpose
- Supportive care
- Intervention model
- Crossover
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 22 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00411255
- Sponsor's protocol ID
- 060192
- Other IDs
- 06-N-0192
- Status last verified
- 19 Feb 2010
- First submitted
- 12 Dec 2006
- Last updated
- 2 Jul 2017
- Results posted
- No
Publications
Antal A, Kincses TZ, Nitsche MA, Bartfai O, Paulus W. Excitability changes induced in the human primary visual cortex by transcranial direct current stimulation: direct electrophysiological evidence. Invest Ophthalmol Vis Sci. 2004 Feb;45(2):702-7. doi: 10.1167/iovs.03-0688.
PubMed 14744917Aramideh M, Koelman JH, Speelman JD, Ongerboer de Visser B. Eyelid movement disorders and electromyography. Lancet. 2001 Mar 10;357(9258):805-6. doi: 10.1016/s0140-6736(05)71235-6. No abstract available.
PubMed 11254003Aramideh M, Eekhof JL, Bour LJ, Koelman JH, Speelman JD, Ongerboer de Visser BW. Electromyography and recovery of the blink reflex in involuntary eyelid closure: a comparative study. J Neurol Neurosurg Psychiatry. 1995 Jun;58(6):692-8. doi: 10.1136/jnnp.58.6.692.
PubMed 7608667
Study at a glance
From the registry record, last updated by the sponsor on 2 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Blepharospasm and the Experimental Modulation of Cortical Excitability in Primary and Secondary Motor Areas. A Pilot Study.
- ClinicalTrials.gov ID
- NCT00411255
- Acronym / sponsor ID
- 060192
- Conditions
- Blepharospasm, Focal Dystonia
- Keywords
- Blink Reflex, Transcranial Magnetic Stimulation (TMS), Dystonia, Blepharospasm, BSP, Focal Dystonia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 22 participants (actual)
- Lead sponsor
- National Institute of Neurological Disorders and Stroke (NINDS)US National Institutes of Health
- Study start
- 22 Jun 2006
- Primary completion
- 7 Apr 2009 (actual)
- Study completion
- 7 Apr 2009 (actual)
- First posted
- 13 Dec 2006 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This research study will examine whether magnetic or electrical stimulation of the brain can improve the involuntary closure of the eyelids in patients with blepharospasm or Meige syndrome; conditions that belong to a group of neurological disorders called dystonias. Blepharospasm and Meige syndrome cause excessive involuntary closure of the eyelids or blinking. In an earlier study of patients with writer's cramp, which is another form of dystonia, symptoms improved temporarily with brain stimulation.
Interested people 18 years of age or older with blepharospasm or Meige syndrome may be eligible for this study. Candidates are screened with a medical history, physical examination and a blink reflex test.
Participants undergo brain stimulation and evaluations before and after the stimulation to test the response, as follows:
Procedures
- Transcranial magnetic stimulation (TMS): A wire coil is held on the patient's scalp. A brief electrical current is passed through the coil, creating a magnetic pulse that stimulates the brain. The subject hears a click and may feel a pulling sensation on the skin under the coil. There may be a twitch in the muscles of the face, arm or leg. The subject may be asked to tense certain muscles slightly or perform other simple actions. The effect of TMS on the muscles is detected with small metal disk electrodes taped to the skin of the arms or legs. TMS is done on eight of the ten test days.
- Repetitive TMS (rTMS): The same procedure as TMS, except repeated magnetic pulses are delivered in short bursts. RTMS is done on eight of the ten test days.
- Theta burst stimulation (TBS): A form of rTMS that involves short bursts of impulses. TBS is done on four study days.
- Cathodal transcranial DC stimulation (tDCS): Two conductive-rubber electrodes placed in saline-soaked sponges are positioned over two areas of the head. A constant weak electrical current flow is applied for 20 minutes. tDCS is done on two study days.
Evaluations
- Physician observation: The subject's eyes are videotaped for 5 minutes before and after each TMS session. A physician then counts how many times the subject blinked during the 5 minutes.
- Questionnaire: Subjects are asked to rate their symptoms before and after brain stimulation.
- Electrophysiological test of the blink reflex: Wires are taped to the skin on the nose and temple to record the eye movement during blinking. A thin plastic rod is placed on the skin over the right e...
Detailed description
BACKGROUND: Blepharospasm (BSP) is a common form of focal dystonia, but the etiology and underlying pathophysiological mechanisms are still obscure. BSP is characterized by excessive involuntary closure of the eyelids. Pathological changes in excitability in the primary motor cortex (MC) and secondary motor areas, such as the anterior cingulate (AC), pre-and supplementary cortex (PMC, SMA) are suggested from electrophysiological and brain imaging studies. It is conceivable that modulation of excitability in some of these areas may lead to amelioration of the symptoms of BSP. Cortical excitability can be experimentally changed by various well-established electrophysiological techniques non-invasively.
METHODS: In this pilot protocol, studying 30 patients with BSP, we will use repetitive transcranial magnetic stimulation (rTMS) over the AC, PMC, SMA and MC in two different inhibitory modes: low frequency rTMS ((lf) rTMS) and continuous theta burst stimulation cTBS. Furthermore, we will apply transcranial direct stimulation (tDCS) in an inhibitory mode (cathodal tDCS) over the MC and low intensity high frequency supraorbital electrical stimulation; the latter will be performed in patients and in 7 healthy subjects. The effects on blepharospasm will be objectively measured by electrophysiological measures (blink reflex recovery curve (BRR), blink rate observation by an investigator blinded to the intervention, and a subjective rating by the patient.
OBJECTIVES: We hypothesize that we will find variable amounts of clinical improvement in BSP patients with these different methods. With this study, we aim to get more insight to the underlying pathophysiological mechanisms of BSP and identify which method of non-invasive brain stimulation may be clinically most efficacious.
Study design
- Primary purpose
- Supportive care
- Intervention model
- Crossover
- Masking
- Single blind (participant)
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Patients with idiopathic BSP or Meige-Syndrome (=BSP plus oromandibular dystonia).
- Age 18 years or older.
- Normal findings in the medical history, physical and neurological examination, except for dystonia (in cases that patients have not had an H\& P at the NIH within the last 12 months; they will undergo all these exams on the first study day).
- Last treatment with botulinum toxin more than three months ago.
- Age 18 years or older
Key exclusion criteria (13 listed)
- Other disease with involuntary blinking (Hemifacial spasm, Tic disorder, Tardive Dyskinesia, Tardive dystonia, etc).
- BSP and normal recovery of R2 in BRR.
- Participation in a clinical trial in the 2 weeks preceding the study.
- History of seizure disorder.
- Pregnancy- a pregnancy test will be performed for women of childbearing potential.
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 |
|---|---|---|
| repetitive transcranial magnetic stimulation (rTMS)Three arms on three different days 180 stimuli will be delivered to the AC with a sham coil, with the H-coil and with a standard circular coil in separate sessions. | Procedure or surgery | – |
Primary outcome
Not reported in the source record.
1 secondary outcome
Patient report the subject rating of their symptoms before and after intervention.
Time frame: Before, immediately after, and one hour after the intervention.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jul 2017.
- Background: PubMed 14744917Antal A, Kincses TZ, Nitsche MA, Bartfai O, Paulus W. Excitability changes induced in the human primary visual cortex by transcranial direct current stimulation: direct electrophysiological evidence. Invest Ophthalmol Vis Sci. 2004 Feb;45(2):702-7. doi: 10.1167/iovs.03-0688.
- Background: PubMed 11254003Aramideh M, Koelman JH, Speelman JD, Ongerboer de Visser B. Eyelid movement disorders and electromyography. Lancet. 2001 Mar 10;357(9258):805-6. doi: 10.1016/s0140-6736(05)71235-6. No abstract available.
- Background: PubMed 7608667Aramideh M, Eekhof JL, Bour LJ, Koelman JH, Speelman JD, Ongerboer de Visser BW. Electromyography and recovery of the blink reflex in involuntary eyelid closure: a comparative study. J Neurol Neurosurg Psychiatry. 1995 Jun;58(6):692-8. doi: 10.1136/jnnp.58.6.692.
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing repetitive transcranial magnetic stimulation (rTMS) in people with Blepharospasm and Focal Dystonia, run by National Institute of Neurological Disorders and Stroke (NINDS) 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 8 inclusion and 13 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 2 Jul 2017. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00411255, which also lists 3 linked publications.
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 2 Jul 2017.