Movement DisordersNCT03263013
Non-invasive Intermittent Theta Burst Stimulation of the Dorsolateral Prefrontal Cortex in People With Functional Movement Disorders
An observational study of Movement Disorders, run by National Institute of Neurological Disorders and Stroke (NINDS) at 1 site in United States.
Trial summary
Background: Functional movement disorder (FMD) causes involuntary movements, such as spasms, shaking, or jerks. These symptoms are not due to a recognized neurological or medical cause. Researchers want to better understand how the brain works to cause these symptoms. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Movement Disorders
- How many people
- 7 participants
- Where
- 1 siteUnited States
- Study dates
- 29 Mar 2018to 5 Feb 2020
- Phase
- Observational
- 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 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: FMD subjects will be recruited from patients assessed at the HMCS Clinic of NINDS/NIH, from the HMCS database, and from protocol 07-N-0190. Patients who have previously participated in protocol 07-N-0190 will be contacted over the telephone and offered participation in the study.
Who may be able to join
- Diagnosis of clinically definite functional movement disorder (as made by a neurologist)
- Ability to give informed consent
- Male and female participants between 18- 65 years of age
- Participation in protocol 07-N-0190
- Right handed (self-report)
- Ability to comply with all study procedures
- Abstinence from alcohol for at least 48 hrs prior to the study and caffeine on the day ofthe study (based on oral interview)
Who cannot join
- History of significant central nervous system disorders (primary or comorbid) such as neurodegenerative disorders, stroke, movement disorders, multiple sclerosis or epilepsy (clinical exam, MRI findings)
- History of psychotic disorder or bipolar disorder (clinical exam and/or SCID). Current acute mania and psychosis will also be excluded. As some degree of depressive symptoms is common in FMD patients, moderate unipolar depression will not be exclusionary (HAM-D score less than or equal to 18 will not be excluded)
- Current obsessive compulsive disorder (OCD) or post-traumatic stress disorder (PTSD)
- Active illicit substance use within the last 6 months (clinical exam and/or SCID).
- Current suicidal ideation (Columbia-Suicide Severity Rating Scale)
- Disease severity requiring inpatient treatment (clinical exam)
Show all 25Show fewer
- Patients with movement symptoms at rest that may substantially inhibit resolution, comfort, or safety of MRI (clinical exam)
- Previous brain neurosurgery (self-reported history)
- History of head trauma that resulted in loss of consciousness for more than several seconds (self-reported history, TMS safety screening questionnaire, MRI findings)
- Regular use in the past 2 weeks of any of the following classes of medications: antiepileptics (except benzodiazepines, gabapentin and pregabalin), anti-parkinsonian medications, muscle relaxants, opiate medications and tricyclic antidepressants (selfreported history)
- Any history of seizures other than febrile childhood seizures (self-reported history)
- Family history of epilepsy (self-reported history, TMS safety screening)
- Patients with recurring fainting spells (self-reported history, TMS safety screening)
- Significant medical illness, including liver failure, kidney failure, congestive heart failure (clinical exam and/or medical records)
- Patients with documented hearing loss greater than or equal to 15dB at any frequency (medical records)
- Any psychiatric, medical or social condition whether or not listed above, due to which, in the judgment of the PI and after any consults if indicated, participation in the study is not in the best interest of the patient.
- Breastfeeding (self-report)
- NINDS employee/staff
- Subjects who have contraindications to MRI (we will follow the NMR Center guidelines for MR safety). Some of the exclusions are:
- Have non-MRI compatible metal in the body, such as a cardiac pacemaker, brain stimulator, shrapnel, surgical metal, clips in the brain or on blood vessels, cochlear implants, artificial heart valves or ferromagnetic fragments in the eye or oral cavity as these make having an MRI unsafe.
- Unable to lie flat on the back for the expected length of the experiment (50 minutes).
- Have an abnormality on the brain imaging or neurologic examination not related to the diagnosis.
- Uncomfortable being in a small space for the expected length of the experiment (50 minutes).
- Non-removable body piercing or tattoo posing MRI risk
- Pregnancy (urine pregnancy test)
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
About this study
Official title: Non-invasive Intermittent Theta Burst Stimulation of the Dorsolateral Prefrontal Cortex in Patients With Functional Movement Disorders
Background:
Functional movement disorder (FMD) causes involuntary movements, such as spasms, shaking, or jerks. These symptoms are not due to a recognized neurological or medical cause. Researchers want to better understand how the brain works to cause these symptoms.
Read more
Objective:
To test if intermittent theta burst stimulation (iTBS) affects brain areas involved in FMD symptoms. Also, to look at the effect of iTBS on mood and motor symptoms.
Eligibility:
Right-handed people ages 18-65 who have FMD and participated in protocol 07-N-0190
Design:
Participants will have 4 visits.
In Visit 1, participants will be screened with:
Medical history
Physical exam
Urine test
Questionnaires
Visit 1 might also include a brain MRI and functional MRI. The MRI scanner is a cylinder surrounded by a strong magnetic field. They will lie on a table that can slide in and out of the cylinder. For the functional MRI, they will be asked to perform tasks during the MRI scan.
Visit 2 will be 1-2 weeks after Visit 1. Visits 2, 3, and 4 will be no more than 48 hours apart. These include:
Electromyography: Small electrodes are taped to the skin. Muscle activity is recorded while participants receive magnetic stimulation of the brain.
Transcranial magnetic stimulation and iTBS: A wire coil is held on the scalp. A brief electrical current passes through the coil and creates a magnetic pulse to stimulate the brain. During iTBS, participants will sit quietly and watch a nature documentary. They will wear earplugs and a cap.
MRI
Functional MRI
Questionnaires
Read the detailed description
Objectives:
The purpose of this protocol is to investigate feasibility and safety of intermittent theta burst stimulation (iTBS) targeting the left dorsolateral prefrontal cortex (DLPFC) in patients with functional movement disorders (FMD). We further aim at exploring whether iTBS of the DLPFC modulates amygdala activity, by investigating iTBS effects on resting-state fronto-amygdala connectivity and on amygdala BOLD response to valenced stimuli.
Study population:
FMD patients (N=6), aged 18-65 years, admitted at the Human Motor Control Section (HMCS) clinic, who have completed protocol 07-N-0190.
Design:
Participants will undergo four outpatient visits. On Visit #1 (baseline), patients will undergo a screening session to assess their eligibility to participate in the current study. They will undergo neurological and psychiatric assessment, as well as structural and functional magnetic resonance imaging. Intermittent TBS will be performed on three separated visits (Visit #2, #3 and #4; iTBS1, iTBS 2 and iTBS 3). During each visit, participants will receive three iTBS sessions over 1-hour, with a 15-minute interval between sessions. Each session will last 190 seconds and a total of 600 pulses will be delivered. Magnetic field intensity will be set at 120% of that participants observed daily resting motor threshold. The target will be identified using the neuronavigation system Brainsight. Following each iTBS visit, behavioral and functional imaging data will be collected.
Outcome measures:
Our primary outcomes will be to evaluate the safety and feasibility of different doses of iTBS of the left DLPFC in patients with FMD. In addition, in order to investigate amygdala engagement by DLPFC iTBS, the following exploratory outcomes will be analyzed: (1) Amygdala BOLD signal change in response to valenced stimuli, from baseline to iTBS3; (2) Amygdala BOLD signal change in response to valenced stimuli, from baseline to each timepoint (iTBS1- iTBS3), for each valence stimuli; (3) Change in fronto-amygdalar resting state functional connectivity, from baseline to iTBS3 (z-score); (4) Change in fronto-amygdalar resting state functional connectivity from baseline to each time point (iTBS1- iTBS3); (5) Change in the valence and arousal subjective levels, using the self-assessment Manikin, from baseline to each time point (iTBS1- iTBS3); (6) Correlations of percent amygdala BOLD signal change with changes in arousal and valence level; (7) Change in the scores on the simplified version of the FMD-RS from pre- to post treatment, for each timepoint.
- Conditions
- Movement Disorders
- Keywords
- Functional (BOLD) MRI
- Medical subject headings
- Movement Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| FMD patients | patients with a diagnosis of clinically definite FMD who have been assessed at the HMCS clinic, and who have completed protocol 07-N-0190. |
What is being measured
The primary outcome is the main question the study is designed to answer.
to evaluate the safety and feasibility of different doses of iTBS of the left DLPFC in patients with FMD.
Percent of subjects experiencing adverse events (i.e., seizures, etc.)
Measured: throughout life of the protocol
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Aug 2017
- Study start29 Mar 2018
- Primary completion5 Feb 2020
- Study completion5 Feb 2020
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 Movement DisordersStudies 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
- Observational
- Observational model
- Case only
- Time perspective
- Prospective
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Mark Hallett, M.D., Principal investigator, National Institute of Neurological Disorders and Stroke (NINDS)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03263013
- Sponsor's protocol ID
- 170160
- Other IDs
- 17-N-0160
- Status last verified
- Jul 2021
- First submitted
- 25 Aug 2017
- Last updated
- 22 Jul 2021
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Stone J, Carson A, Duncan R, Roberts R, Coleman R, Warlow C, Murray G, Pelosi A, Cavanagh J, Matthews K, Goldbeck R, Sharpe M. Which neurological diseases are most likely to be associated with "symptoms unexplained by organic disease". J Neurol. 2012 Jan;259(1):33-8. doi: 10.1007/s00415-011-6111-0. Epub 2011 Jun 16.
PubMed 21674198Carson A, Stone J, Hibberd C, Murray G, Duncan R, Coleman R, Warlow C, Roberts R, Pelosi A, Cavanagh J, Matthews K, Goldbeck R, Hansen C, Sharpe M. Disability, distress and unemployment in neurology outpatients with symptoms 'unexplained by organic disease'. J Neurol Neurosurg Psychiatry. 2011 Jul;82(7):810-3. doi: 10.1136/jnnp.2010.220640. Epub 2011 Jan 21.
PubMed 21257981Gelauff J, Stone J, Edwards M, Carson A. The prognosis of functional (psychogenic) motor symptoms: a systematic review. J Neurol Neurosurg Psychiatry. 2014 Feb;85(2):220-6. doi: 10.1136/jnnp-2013-305321. Epub 2013 Sep 12.
PubMed 24029543
Study at a glance
From the registry record, last updated by the sponsor on 22 Jul 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Non-invasive Intermittent Theta Burst Stimulation of the Dorsolateral Prefrontal Cortex in Patients With Functional Movement Disorders
- ClinicalTrials.gov ID
- NCT03263013
- Acronym / sponsor ID
- 170160
- Conditions
- Movement Disorders
- Keywords
- Functional (BOLD) MRI
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 7 participants (actual)
- Lead sponsor
- National Institute of Neurological Disorders and Stroke (NINDS)US National Institutes of Health
- Study start
- 29 Mar 2018 (actual)
- Primary completion
- 5 Feb 2020 (actual)
- Study completion
- 5 Feb 2020 (actual)
- First posted
- 28 Aug 2017 (actual)
- 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.
Background:
Functional movement disorder (FMD) causes involuntary movements, such as spasms, shaking, or jerks. These symptoms are not due to a recognized neurological or medical cause. Researchers want to better understand how the brain works to cause these symptoms.
Objective:
To test if intermittent theta burst stimulation (iTBS) affects brain areas involved in FMD symptoms. Also, to look at the effect of iTBS on mood and motor symptoms.
Eligibility:
Right-handed people ages 18-65 who have FMD and participated in protocol 07-N-0190
Design:
Participants will have 4 visits.
In Visit 1, participants will be screened with:
Medical history
Physical exam
Urine test
Questionnaires
Visit 1 might also include a brain MRI and functional MRI. The MRI scanner is a cylinder surrounded by a strong magnetic field. They will lie on a table that can slide in and out of the cylinder. For the functional MRI, they will be asked to perform tasks during the MRI scan.
Visit 2 will be 1-2 weeks after Visit 1. Visits 2, 3, and 4 will be no more than 48 hours apart. These include:
Electromyography: Small electrodes are taped to the skin. Muscle activity is recorded while participants receive magnetic stimulation of the brain.
Transcranial magnetic stimulation and iTBS: A wire coil is held on the scalp. A brief electrical current passes through the coil and creates a magnetic pulse to stimulate the brain. During iTBS, participants will sit quietly and watch a nature documentary. They will wear earplugs and a cap.
MRI
Functional MRI
Questionnaires
Detailed description
Objectives:
The purpose of this protocol is to investigate feasibility and safety of intermittent theta burst stimulation (iTBS) targeting the left dorsolateral prefrontal cortex (DLPFC) in patients with functional movement disorders (FMD). We further aim at exploring whether iTBS of the DLPFC modulates amygdala activity, by investigating iTBS effects on resting-state fronto-amygdala connectivity and on amygdala BOLD response to valenced stimuli.
Study population:
FMD patients (N=6), aged 18-65 years, admitted at the Human Motor Control Section (HMCS) clinic, who have completed protocol 07-N-0190.
Design:
Participants will undergo four outpatient visits. On Visit #1 (baseline), patients will undergo a screening session to assess their eligibility to participate in the current study. They will undergo neurological and psychiatric assessment, as well as structural and functional magnetic resonance imaging. Intermittent TBS will be performed on three separated visits (Visit #2, #3 and #4; iTBS1, iTBS 2 and iTBS 3). During each visit, participants will receive three iTBS sessions over 1-hour, with a 15-minute interval between sessions. Each session will last 190 seconds and a total of 600 pulses will be delivered. Magnetic field intensity will be set at 120% of that participants observed daily resting motor threshold. The target will be identified using the neuronavigation system Brainsight. Following each iTBS visit, behavioral and functional imaging data will be collected.
Outcome measures:
Our primary outcomes will be to evaluate the safety and feasibility of different doses of iTBS of the left DLPFC in patients with FMD. In addition, in order to investigate amygdala engagement by DLPFC iTBS, the following exploratory outcomes will be analyzed: (1) Amygdala BOLD signal change in response to valenced stimuli, from baseline to iTBS3; (2) Amygdala BOLD signal change in response to valenced stimuli, from baseline to each timepoint (iTBS1- iTBS3), for each valence stimuli; (3) Change in fronto-amygdalar resting state functional connectivity, from baseline to iTBS3 (z-score); (4) Change in fronto-amygdalar resting state functional connectivity from baseline to each time point (iTBS1- iTBS3); (5) Change in the valence and arousal subjective levels, using the self-assessment Manikin, from baseline to each time point (iTBS1- iTBS3); (6) Correlations of percent amygdala BOLD signal change with changes in arousal and valence level; (7) Change in the scores on the simplified version of the FMD-RS from pre- to post treatment, for each timepoint.
Study design
- Observational model
- Case only
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| FMD patients | – | –patients with a diagnosis of clinically definite FMD who have been assessed at the HMCS clinic, and who have completed protocol 07-N-0190. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- FMD subjects will be recruited from patients assessed at the HMCS Clinic of NINDS/NIH, from the HMCS database, and from protocol 07-N-0190. Patients who have previously participated in protocol 07-N-0190 will be contacted over the telephone and offered participation in the study.
Key inclusion criteria (7 listed)
- Diagnosis of clinically definite functional movement disorder (as made by a neurologist)
- Ability to give informed consent
- Male and female participants between 18- 65 years of age
- Participation in protocol 07-N-0190
- Right handed (self-report)
Key exclusion criteria (25 listed)
- History of significant central nervous system disorders (primary or comorbid) such as neurodegenerative disorders, stroke, movement disorders, multiple sclerosis or epilepsy (clinical exam, MRI findings)
- History of psychotic disorder or bipolar disorder (clinical exam and/or SCID). Current acute mania and psychosis will also be excluded. As some degree of depressive symptoms is common in FMD patients, moderate unipolar depression will not be exclusionary (HAM-D score less than or equal to 18 will not be excluded)
- Current obsessive compulsive disorder (OCD) or post-traumatic stress disorder (PTSD)
- Active illicit substance use within the last 6 months (clinical exam and/or SCID).
- Current suicidal ideation (Columbia-Suicide Severity Rating Scale)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
to evaluate the safety and feasibility of different doses of iTBS of the left DLPFC in patients with FMD.
Time frame: throughout life of the protocol
Percent of subjects experiencing adverse events (i.e., seizures, etc.)
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 22 Jul 2021.
- Background: PubMed 21674198Stone J, Carson A, Duncan R, Roberts R, Coleman R, Warlow C, Murray G, Pelosi A, Cavanagh J, Matthews K, Goldbeck R, Sharpe M. Which neurological diseases are most likely to be associated with "symptoms unexplained by organic disease". J Neurol. 2012 Jan;259(1):33-8. doi: 10.1007/s00415-011-6111-0. Epub 2011 Jun 16.
- Background: PubMed 21257981Carson A, Stone J, Hibberd C, Murray G, Duncan R, Coleman R, Warlow C, Roberts R, Pelosi A, Cavanagh J, Matthews K, Goldbeck R, Hansen C, Sharpe M. Disability, distress and unemployment in neurology outpatients with symptoms 'unexplained by organic disease'. J Neurol Neurosurg Psychiatry. 2011 Jul;82(7):810-3. doi: 10.1136/jnnp.2010.220640. Epub 2011 Jan 21.
- Background: PubMed 24029543Gelauff J, Stone J, Edwards M, Carson A. The prognosis of functional (psychogenic) motor symptoms: a systematic review. J Neurol Neurosurg Psychiatry. 2014 Feb;85(2):220-6. doi: 10.1136/jnnp-2013-305321. Epub 2013 Sep 12.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
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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.
Mark Hallett, M.D. principal investigator
National Institute of Neurological Disorders and Stroke (NINDS)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Movement Disorders, 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 7 inclusion and 25 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 22 Jul 2021. 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.
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.
What does the primary outcome measure?
to evaluate the safety and feasibility of different doses of iTBS of the left DLPFC in patients with FMD. (time frame: throughout life of the protocol). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03263013, 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 22 Jul 2021.