Writer's CrampEarly Phase 1NCT02504905
Propensity to Develop Plasticity in the Parieto-Motor Networks in Dystonia From the Perspective of Abnormal High-Order Motor Processing
A Early Phase 1 study testing TMS in people with Writer's Cramp and Healthy Volunteers, run by National Institute of Neurological Disorders and Stroke (NINDS) at 1 site in United States.
Trial summary
Background: People with dystonia have muscle contractions they can t control. These cause slow, repeated motions or abnormal postures. People with dystonia have abnormalities in certain parts of the brain. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Writer's Cramp, Healthy Volunteers, Cervical Dystonia
- What is being tested?
- TMS
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 58 participants
- Where
- 1 siteUnited States
- Study dates
- 20 Aug 2015to 25 Jul 2021
- Phase
- Early Phase 1
- 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
Who may be able to join
- Between the ages of 18 and 65 years
- Right-handed
- English speaking
- For patients only: confirmed diagnosis of cervical dystonia (PAR-CD) or writer s cramp (PAR-WC).
- For patients treated with anticholinergics and/or benzodiazepines, they must be willing and safely able to abstain from any of these medication for a period of at least 5 plasma half-lives of the individual drug prior to study participation (2 days for trihexyphenidyl which has a plasma half life around 4 hours; 12 days, for clonazepam which has a half-life of 18-50 hours).
- For HVs only: absence of dystonia or other neurological disorder with any effect on the motor or sensory systems
- Ability to give informed consent
- Ability to comply with all study procedures, based on the judgment by the investigator(s).
Who cannot join
- Any of the following will exclude patients from the study:
- Secondary forms of dystonia, including tardive dyskinesia.
- Dystonic tremor where the tremor is the sole or principal abnormality.
- Botulinum toxin treatment < 3 months prior to visit.
- Any of the following will exclude patients or healthy controls from the study:
- Illegal drug use within the past 6 months based on history alone. The intent is to exclude those with drug use that may affect study results.
Show all 18Show fewer
- Self-reported consumption of 7 alcoholic drinks a week for women and >14 alcoholic drinks a week for man.
- Abnormal findings on neurologic exam (other than dystonia in patient group).
- History of or current brain tumor, stroke, head trauma with loss of consciousness > few seconds, epilepsy or seizures.
- Current diagnosis of major depression or any major mental disorders (axis I disorders).
- Current diagnosis of neurologic disorder other than dystonia.
- Presence of pacemaker, intracardiac lines, implanted pumps or stimulators, or metal objects inside the eye or skull. Dental fillings and dental braces are allowed.
- Known hearing loss.
- Open scalp wounds or scalp infection.
- Current pregnancy.
- Taking benzodiazepines at the time of the study or within 12 days prior to the study.
- Taking anticholinergics at the time of the study or within 2 days prior to the study.
- Taking at the time of the study or within 2 weeks prior to the study any medication that acts as a central nervous system stimulant or that is known to lower seizure threshold, including, imipramine, amitriptyline, doxepine, nortriptyline, maprotiline, chlorpromazine, foscarnet, ganciclovir, ritonavir, amphetamines, ketamine, gamma-hydroxybutyrate (GHB), theophylline, mianserin, fluoxetine, fluvoxamine, paroxetine, sertraline, citalopram, reboxetine, venlafaxine, duloxetine, bupropion, mirtazapine, fluphenazine, pimozide, haloperidol, olanzapine, quetiapine, aripiprazole, ziprasidone, risperidone, chloroquine, mefloquine, imipenem, penicillin, ampicillin, cephalosporins, metronidazole, isoniazid, levofloxacin, cyclosporin, chlorambucil, vincristine, methotrexate, cytosine arabinoside, BCNU, lithium, antihistamines, and sympathomimetics.
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: Propensity to Develop Plasticity in the Parieto-motor Network in Dystonia From the Perspective of Abnormal High-Order Motor Processing
Background:
- People with dystonia have muscle contractions they can t control. These cause slow, repeated motions or abnormal postures. People with dystonia have abnormalities in certain parts of the brain. Researchers want to study the activity of two different brain areas in people with writer s cramp and cervical dystonia.
Read more
Objective:
- To compare brain activity in people with dystonia to that in healthy people.
Eligibility:
- Right-handed people ages of 18-65 with cervical dystonia or writer s cramp.
- Healthy volunteers the same ages.
Design:
- Participants will be screened with a physical exam. They will answer questions about being right- or left-handed.
- At study visit 1, participants will:<TAB>
- Have a neurological exam.
- Answer questions about how their disease impacts their daily activities.
- Have a structural magnetic resonance imaging (MRI) scan. Participants will lie on a table that can slide <TAB>in and out of a metal cylinder. This is surrounded by a strong magnetic field.
- Do 2 simple computer tasks.
- At study visit 2:
- Participants will have transcranial magnetic stimulations (TMS) at 2 places on the head. Two wire coils will be held on the scalp. A brief electrical current creates a magnetic pulse that affects brain activity. Muscles of the face, arm, or leg might twitch. Participants may have to tense certain muscles or do simple tasks during TMS. They may be asked to rate any discomfort caused by TMS.
- Muscle activity in the right hand will be recorded by electrodes stuck to the skin of that hand.
Read the detailed description
Objective:
The purpose of this protocol is to improve understanding of the pathophysiology of dystonia by performing an electrophysiological study using plasticity induction protocols based on dual-site transcranial magnetic stimulation (TMS). We hypothesize that dystonic patients have enhanced responsiveness to plasticity induction in the parieto-motor network. The clinical significance of such an enhanced plasticity will be evaluated by correlating the plasticity measurements with subjects' performance on two tasks engaging high-order motor processing and involving the parietal cortex.
Study population
This study will explore the parieto-motor network (PAR study). There will be two independent arms in each study: one will compare patients with writer s cramp (WC) and age-matched healthy volunteers (HV); and the other one will compare patients with cervical dystonia (CD) with age-matched HVs. The power analysis of thePAR study indicates that we need to enroll 17 patients and 17 healthy volunteers in each arm, with an additional 3 added to account for drop-outs. Therefore, we request a maximum of 20 subjects per patient group and 40 subjects for the control groups.
Design
Subjects will come for one screening visit and two outpatient study visits. During the first study visit patients will be scored clinically for dystonia. They will also undergo a structural magnetic resonance imaging (MRI) to locate the parietal target during the stimulation session. At least 24 hours later, during study visit two, subjects will receive TMS. TMS-induced electromyographic (EMG) activity of hand muscles will be recorded as motor evoked potentials (MEPs). Using single TMS shocks, we will measure at baseline, the input-output (I-O) curve for the right first dorsal interosseous (FDI) muscle MEPs. Then, the subjects will receive a plasticity induction protocol aiming to induce plasticity in the pathway linking the posterior parietal (PP) cortex and the primary motor cortex (M1). To that end, transcranial stimulation will be applied repeatedly (100 pairs) to the left angular gyrus in the PP cortex and to the left M1. At the end of the intervention, the I-O curve will be measured again over the next 50 minutes.
Outcome measures
The amplitude of the MEPs in the I-O curves gives information about corticospinal excitability as a function of TMS stimulation. The primary outcome measure will be the relative change of the MEP size with respect to time (before and 15-20 min after the plasticity intervention). The difference in MEP size will be compared between the HV and the patient groups using a T test.
- Conditions
- Writer's Cramp, Healthy Volunteers, Cervical Dystonia
- Being tested
- TMS
- Keywords
- Parietal Lobe, Plasticity, Dystonia, Transcranial Magnetic Stimulation (TMS)
- Medical subject headings
- Dystonic Disorders, Torticollis, Dystonia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TMSDevice
single TMS pulses at intensities in random order from 0 to 100% (increasing at 5% intervals) of stimulator output at a frequency of 0.1 Hz. Three pulses will be delivered at each intensity. MEPs will be recorded and their amplitudes will be plotted against the corresponding stimulation intensity. This curve will provide three significant parameters: (a) S50 intensity (intensity for which we get a MEP 50 % of its maximal size); (b) estimated resting motor threshold (RMT): the abscissa where the tangent to the slope crosses the x axis; and (c) the maximum MEP ( plateau value).
| Study group | Role | What they receive |
|---|---|---|
| PAR-CD | Experimental | CD and age/sex matched HV control Receives: Device: TMS |
| PAR-WC | Experimental | WC and age/sex matched HV control Receives: Device: TMS |
What is being measured
The primary outcome is the main question the study is designed to answer.
MEP size at S50 with respect to time (before, and 15-20 min after PAS intervention)
The size of the MEP in the EMG signal gives information about corticospinal excitability as a function of TMS stimulation. An increase in average MEP after the end of PAS intervention implies development of LTP-like plasticity in the pathway linking the parietal cortex or the cerebellum to M1. A decrease would imply development of LTD-like plasticity.
Measured: throughout
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jul 2015 (estimated)
- Study start20 Aug 2015
- Primary completion25 Jul 2021
- Study completion25 Jul 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Writer's CrampStudies of the same condition, open and under way.
- 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
- Early Phase 1
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Factorial
- Masking
- None (open label)
- Enrolment
- 58 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Institute of Neurological Disorders and Stroke (NINDS)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Hyun Joo Cho, M.D., Principal investigator, National Institute of Neurological Disorders and Stroke (NINDS)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02504905
- Sponsor's protocol ID
- 150167
- Other IDs
- 15-N-0167
- Status last verified
- Mar 2025
- First submitted
- 21 Jul 2015
- Last updated
- 5 Mar 2025
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: This protocol pre-dates plans to share IPD, we expect to share deidentified data after publication upon request to comply with NIH policies.
Study at a glance
From the registry record, last updated by the sponsor on 5 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Propensity to Develop Plasticity in the Parieto-motor Network in Dystonia From the Perspective of Abnormal High-Order Motor Processing
- ClinicalTrials.gov ID
- NCT02504905
- Acronym / sponsor ID
- 150167
- Conditions
- Writer's Cramp, Healthy Volunteers, Cervical Dystonia
- Keywords
- Parietal Lobe, Plasticity, Dystonia, Transcranial Magnetic Stimulation (TMS)
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 58 participants (actual)
- Lead sponsor
- National Institute of Neurological Disorders and Stroke (NINDS)US National Institutes of Health
- Study start
- 20 Aug 2015 (actual)
- Primary completion
- 25 Jul 2021 (actual)
- Study completion
- 25 Jul 2021 (actual)
- First posted
- 22 Jul 2015 (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.
Background:
- People with dystonia have muscle contractions they can t control. These cause slow, repeated motions or abnormal postures. People with dystonia have abnormalities in certain parts of the brain. Researchers want to study the activity of two different brain areas in people with writer s cramp and cervical dystonia.
Objective:
- To compare brain activity in people with dystonia to that in healthy people.
Eligibility:
- Right-handed people ages of 18-65 with cervical dystonia or writer s cramp.
- Healthy volunteers the same ages.
Design:
- Participants will be screened with a physical exam. They will answer questions about being right- or left-handed.
- At study visit 1, participants will:<TAB>
- Have a neurological exam.
- Answer questions about how their disease impacts their daily activities.
- Have a structural magnetic resonance imaging (MRI) scan. Participants will lie on a table that can slide <TAB>in and out of a metal cylinder. This is surrounded by a strong magnetic field.
- Do 2 simple computer tasks.
- At study visit 2:
- Participants will have transcranial magnetic stimulations (TMS) at 2 places on the head. Two wire coils will be held on the scalp. A brief electrical current creates a magnetic pulse that affects brain activity. Muscles of the face, arm, or leg might twitch. Participants may have to tense certain muscles or do simple tasks during TMS. They may be asked to rate any discomfort caused by TMS.
- Muscle activity in the right hand will be recorded by electrodes stuck to the skin of that hand.
Detailed description
Objective:
The purpose of this protocol is to improve understanding of the pathophysiology of dystonia by performing an electrophysiological study using plasticity induction protocols based on dual-site transcranial magnetic stimulation (TMS). We hypothesize that dystonic patients have enhanced responsiveness to plasticity induction in the parieto-motor network. The clinical significance of such an enhanced plasticity will be evaluated by correlating the plasticity measurements with subjects' performance on two tasks engaging high-order motor processing and involving the parietal cortex.
Study population
This study will explore the parieto-motor network (PAR study). There will be two independent arms in each study: one will compare patients with writer s cramp (WC) and age-matched healthy volunteers (HV); and the other one will compare patients with cervical dystonia (CD) with age-matched HVs. The power analysis of thePAR study indicates that we need to enroll 17 patients and 17 healthy volunteers in each arm, with an additional 3 added to account for drop-outs. Therefore, we request a maximum of 20 subjects per patient group and 40 subjects for the control groups.
Design
Subjects will come for one screening visit and two outpatient study visits. During the first study visit patients will be scored clinically for dystonia. They will also undergo a structural magnetic resonance imaging (MRI) to locate the parietal target during the stimulation session. At least 24 hours later, during study visit two, subjects will receive TMS. TMS-induced electromyographic (EMG) activity of hand muscles will be recorded as motor evoked potentials (MEPs). Using single TMS shocks, we will measure at baseline, the input-output (I-O) curve for the right first dorsal interosseous (FDI) muscle MEPs. Then, the subjects will receive a plasticity induction protocol aiming to induce plasticity in the pathway linking the posterior parietal (PP) cortex and the primary motor cortex (M1). To that end, transcranial stimulation will be applied repeatedly (100 pairs) to the left angular gyrus in the PP cortex and to the left M1. At the end of the intervention, the I-O curve will be measured again over the next 50 minutes.
Outcome measures
The amplitude of the MEPs in the I-O curves gives information about corticospinal excitability as a function of TMS stimulation. The primary outcome measure will be the relative change of the MEP size with respect to time (before and 15-20 min after the plasticity intervention). The difference in MEP size will be compared between the HV and the patient groups using a T test.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Factorial
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| PAR-CD | Experimental | Device: TMSCD and age/sex matched HV control |
| PAR-WC | Experimental | Device: TMSWC and age/sex matched HV control |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Between the ages of 18 and 65 years
- Right-handed
- English speaking
- For patients only: confirmed diagnosis of cervical dystonia (PAR-CD) or writer s cramp (PAR-WC).
- For patients treated with anticholinergics and/or benzodiazepines, they must be willing and safely able to abstain from any of these medication for a period of at least 5 plasma half-lives of the individual drug prior to study participation (2 days for trihexyphenidyl which has a plasma half life around 4 hours; 12 days, for clonazepam which has a half-life of 18-50 hours).
Key exclusion criteria (18 listed)
- Secondary forms of dystonia, including tardive dyskinesia.
- Dystonic tremor where the tremor is the sole or principal abnormality.
- Botulinum toxin treatment < 3 months prior to visit.
- Illegal drug use within the past 6 months based on history alone. The intent is to exclude those with drug use that may affect study results.
- Self-reported consumption of 7 alcoholic drinks a week for women and >14 alcoholic drinks a week for man.
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 |
|---|---|---|
| TMSsingle TMS pulses at intensities in random order from 0 to 100% (increasing at 5% intervals) of stimulator output at a frequency of 0.1 Hz. Three pulses will be delivered at each intensity. MEPs will be recorded and their amplitudes will be plotted against the corresponding stimulation intensity. This curve will provide three significant parameters: (a) S50 intensity (intensity for which we get a MEP 50 % of its maximal size); (b) estimated resting motor threshold (RMT): the abscissa where the tangent to the slope crosses the x axis; and (c) the maximum MEP ( plateau value). | Device | PAR-CD, PAR-WC |
Primary outcome
MEP size at S50 with respect to time (before, and 15-20 min after PAS intervention)
Time frame: throughout
The size of the MEP in the EMG signal gives information about corticospinal excitability as a function of TMS stimulation. An increase in average MEP after the end of PAS intervention implies development of LTP-like plasticity in the pathway linking the parietal cortex or the cerebellum to M1. A decrease would imply development of LTD-like plasticity.
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 5 Mar 2025.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- Individual participant dataSharing planned: Undecided. This protocol pre-dates plans to share IPD, we expect to share deidentified data after publication upon request to comply with NIH policies.
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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.
Hyun Joo Cho, 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?
A Early Phase 1 study testing TMS in people with Writer's Cramp and Healthy Volunteers, 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 18 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 5 Mar 2025. 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?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
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.
What does the primary outcome measure?
MEP size at S50 with respect to time (before, and 15-20 min after PAS intervention) (time frame: throughout). 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 5 Mar 2025.