Focal DystoniaNCT03206112
Loss of Depotentiation in Focal Dystonia
An observational study of Focal Dystonia and Healthy Volunteers, run by National Institute of Neurological Disorders and Stroke (NINDS) at 1 site in United States.
Trial summary
Background Focal dystonia is a brain disorder. It affects a muscle or muscles in a specific part of the body. Researchers think it may be related to excessive training or practice. They want to know more about how much training might trigger focal dystonia. Objectives: To study why people develop focal dystonia. Read more about this study
- Who is it for?
- Ages 18 to 70 yearsHealthy volunteers can take part
- Conditions the study is for
- Focal Dystonia, Healthy Volunteers
- What is being tested?
- PAS25, PAS10 and PAS25-cTBS150
- How many people
- 6 participants
- Where
- 1 siteUnited States
- Study dates
- 20 Sep 2017to 9 Apr 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 70 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Subjects (patients and healthy volunteers) are recruited through the NIH Patient Recruitment and Public Liaison Office and from individuals who have participated in prior studies and are interested in being contacted for additional studies. Additionally, individuals who have contacted NIH to volunteer for research studies will be considered for recruitment.
Who may be able to join
- At least 18 years old.*
- Able to give informed consent.
- Able to comply with all study procedures.
- Abstain from alcohol for at least 48 hours prior to each study visit and caffeine on the day of the visit.
- Have no neurological or psychiatric disorders established by history and physical/neurological examination.
- = A maximum of 10 subjects who are over the age of 70 will be screened for plasticity. If none of these subjects have plasticity, we will not accrue any more subjects over the age of 70.
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- At least 18-years old.*
- Able to give informed consent.
- Able to comply with all study procedures.
- Abstain from alcohol for at least 48 hours prior to each visit of the study and caffeine on the day of the visit.
- Have an established diagnosis of focal dystonia.
- No botulinum toxin injections at least in the past 3 months.
- = A maximum of 10 subjects who are over the age of 70 will be screened for plasticity. If none of these subjects have plasticity, we will not accrue any more subjects over the age of 70.
Who cannot join
- Self-reported consumption of > 14 alcoholic drinks/week for a man and > 7 alcoholic drinks/week for a woman.
- Focal dystonia patients: presence of abnormal findings on neurological examination except for the diagnosis of focal dystonia. Healthy volunteers: no abnormal findings on neurological examination.
- History of or current brain tumor, stroke, head trauma with loss of consciousness, epilepsy or seizures.
- Have a Baclofen pump, or have neurostimulators for pain.
- Pregnant or breastfeeding women.
- Current episode of major depression or any major psychiatric illness.
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- Presence of any metal in the eye or skull area such as a brain stimulator, shrapnel, surgical metal, clips in the brain, cochlear implants, metal fragments in the eye.
- Presence of pacemaker, intracardiac lines, implanted pumps or stimulators.
- Known hearing loss.
- Cognitive impairment.
- NIH staff from HMCS.
- Healthy Volunteers:
- -Taking medications that act directly on the central nervous system such as anti- epileptics, anti-histamines, anti-parkinsonian medication, medication for insomnia, anti-depressants, anti-anxiety medication.
- Focal Dystonia Patients:
- -Taking medications that act directly on the central nervous system such as anti- epileptics, anti-parkinsonian medication, medication for insomnia.
- NOTE: Patients taking anti-histamines, anti-depressants or anti-anxiety medications will not be excluded from the protocol. However, only patients who have mild symptoms and agree to temporarily stop the medications during the experiment will be included.
- Patients with mild symptoms of depression will be confirmed using Hamilton Depression Rating Scale with total scores below 13. Patients with mild symptoms of anxiety will be confirmed using Hamilton Anxiety Rating Scale with total scores below 17. Patients will be required to stop their medication at least 5 half- lives of the drug, but no longer than 5 days (even if the half-life is longer than 24 hours) before each experimental session.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
About this study
Background
Focal dystonia is a brain disorder. It affects a muscle or muscles in a specific part of the body. Researchers think it may be related to excessive training or practice. They want to know more about how much training might trigger focal dystonia.
Read more
Objectives:
To study why people develop focal dystonia. To study how brain plasticity changes with focal dystonia.
Eligibility:
People at least 18 years of age with focal dystonia.
Healthy volunteers the same age are also needed.
Design:
Participants will be screened with a physical exam and questions. They may have blood and urine tests.
Participants will have up to 3 testing visits.
Participants will have small electrodes stuck on the skin on the hands or arms. Muscle activity will be recorded.
Participants will have transcranial magnetic stimulation (TMS). A wire coil will be placed onto the scalp. A brief electrical current will pass through the coil. The current will create a magnetic field that affects brain activity.
Participants may be asked to tense certain muscles or do simple actions during TMS.
A nerve at the wrist will get weak electrical stimulation. The stimulation may be paired with TMS for very short times.
Participants will receive repeated magnetic pulses. Participants will receive a total of 150 pulses during a 10-second period. An entire testing visit will last about 3 hours.
...
Read the detailed description
Objectives
Simulation paradigms can induce plastic changes in brain excitability. Paired associative stimulation (PAS) with an interstimulus interval of 25 ms (PAS25) induces a long-term potentiation (LTP)-like effect while that at an interval of 10 ms (PAS10) induces a long-term depression (LTD)-like effect. The LTP-like effect induced by PAS25 is exaggerated in patients with focal dystonia. The LTD-like effect with PAS10 is also increased in focal dystonia but not in the target area of PAS. Depotentiation refers to the reversal of LTP by which LTP is abolished by a following procedure that has no effect when it is given alone. Brain-derived neurotrophic factor has a variety of roles in modulating both LTP and LTD. The Val66Met single nucleotide polymorphism is related to abnormal cortical plasticity. In this protocol, we propose a study to test the hypothesis that depotentiation is weaker in focal dystonia patients compared to healthy controls. In addition, motor cortical inhibition is decreased in focal dystonia. We will test the changes in motor cortical inhibition following different interventional procedures in focal dystonia. We will also test the relationship between depotentiation and LTP/LTD-like effects in focal dystonia patients.
Study population
We intend to study up to 20 patients with focal dystonia and 20 age-matched healthy volunteers. Subjects will complete up to 3 study visits involving 3 different interventional procedures. Various outcome measures will be performed during each study visit.
Design
This is a hypothesis-driven study. We will compare the depotentiation effect in patients with focal dystonia to that in healthy volunteers. Patients will be evaluated with a clinical rating scale during the screening visit. Three interventional procedures will be tested during three study visits. Specifically, PAS25-cTBS150 tests the primary hypothesis with a depotentiation effect. PAS25 tests LTP-like effect and PAS10 tests the LTD-like effect. We will investigate the difference in outcome measures between patients and healthy volunteers after the interventional procedures. We will perform genetic tests to identify the brain-derived neurotrophic factor genotype in the patients and healthy volunteers.
Outcome measures
The primary outcome measure is motor-evoked potential (MEP) induced by transcranial magnetic stimulation immediately after the interventional procedure of PAS25-cTBS150. We will compare MEP amplitude in patients with that in healthy volunteers to identify whether depotentiation is weaker in focal dystonia. The secondary outcome measures are MEP amplitudes at other time points after the PAS25-cTBS150 procedure. We will also perform exploratory studies to investigate the effects of interventional procedures of PAS25 and PAS10 alone. We will test the relationship between depotentiation and LTP/LTD-like effects in focal dystonia. We will also study other exploratory outcome measures such as: resting and active motor threshold, MEP recruitment curve, excitability of motor cortical circuits (short- and long-interval intracortical inhibition, and intracortical facilitation) after three different interventional procedures.
- Conditions
- Focal Dystonia, Healthy Volunteers
- Being tested
- PAS25, PAS10, PAS25-cTBS150
- Keywords
- Focal Dystonia, Healthy Volunteers, Paired Associative Stimulation (PAS)
- Medical subject headings
- Dystonic Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PAS25Other
We will record surface electromyography from the target abductor pollicis brevis muscle and adjacent first dorsal interosseous and abductor digiti minimi muscles.
PAS10Other
We will record surface electromyography from the target abductor pollicis brevis muscle and adjacent first dorsal interosseous and abductor digiti minimi muscles. TBS is a special form of
PAS25-cTBS150Other
We will record surface electromyography from the target abductor pollicis brevis muscle and adjacent first dorsal interosseous and abductor digiti minimi muscles.
| Study group | Role | What they receive |
|---|---|---|
| Focal Dystonia | Subjects diagnosed with Focal Dystonia Receives: Other: PAS25; Other: PAS10; Other: PAS25-cTBS150 | |
| Healthy Volunteers | Healthy Volunteers Receives: Other: PAS25; Other: PAS10; Other: PAS25-cTBS150 |
What is being measured
The primary outcome is the main question the study is designed to answer.
MEP amplitude immediately after the PAS25-cTBS150 (depotentiation) protocol
compare MEP amplitude in patients with that in healthy volunteers to identify whether depotentiation is weaker in focal dystonia
Measured: throughout
Secondary outcomes (1)
MEP amplitudes
MEP amplitudes at other time points after the PAS25-cTBS150 procedure
Measured: throughout
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jul 2017
- Study start20 Sep 2017
- Primary completion9 Apr 2020
- Study completion9 Apr 2020
Why it stopped: PI leaving the NIH
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Focal DystoniaStudies 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-control
- Time perspective
- Cross-sectional
- Enrolment
- 6 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
- NCT03206112
- Sponsor's protocol ID
- 170123
- Other IDs
- 17-N-0123
- Status last verified
- Apr 2020
- First submitted
- 30 Jun 2017
- Last updated
- 6 May 2020
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 May 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Loss of Depotentiation in Focal Dystonia
- ClinicalTrials.gov ID
- NCT03206112
- Acronym / sponsor ID
- 170123
- Conditions
- Focal Dystonia, Healthy Volunteers
- Keywords
- Focal Dystonia, Healthy Volunteers, Paired Associative Stimulation (PAS)
- Study type
- Observational
- Recruitment status
- TerminatedReason stopped: PI leaving the NIH
- Enrolment
- 6 participants (actual)
- Lead sponsor
- National Institute of Neurological Disorders and Stroke (NINDS)US National Institutes of Health
- Study start
- 20 Sep 2017 (actual)
- Primary completion
- 9 Apr 2020 (actual)
- Study completion
- 9 Apr 2020 (actual)
- First posted
- 2 Jul 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
Focal dystonia is a brain disorder. It affects a muscle or muscles in a specific part of the body. Researchers think it may be related to excessive training or practice. They want to know more about how much training might trigger focal dystonia.
Objectives:
To study why people develop focal dystonia. To study how brain plasticity changes with focal dystonia.
Eligibility:
People at least 18 years of age with focal dystonia.
Healthy volunteers the same age are also needed.
Design:
Participants will be screened with a physical exam and questions. They may have blood and urine tests.
Participants will have up to 3 testing visits.
Participants will have small electrodes stuck on the skin on the hands or arms. Muscle activity will be recorded.
Participants will have transcranial magnetic stimulation (TMS). A wire coil will be placed onto the scalp. A brief electrical current will pass through the coil. The current will create a magnetic field that affects brain activity.
Participants may be asked to tense certain muscles or do simple actions during TMS.
A nerve at the wrist will get weak electrical stimulation. The stimulation may be paired with TMS for very short times.
Participants will receive repeated magnetic pulses. Participants will receive a total of 150 pulses during a 10-second period. An entire testing visit will last about 3 hours.
...
Detailed description
Objectives
Simulation paradigms can induce plastic changes in brain excitability. Paired associative stimulation (PAS) with an interstimulus interval of 25 ms (PAS25) induces a long-term potentiation (LTP)-like effect while that at an interval of 10 ms (PAS10) induces a long-term depression (LTD)-like effect. The LTP-like effect induced by PAS25 is exaggerated in patients with focal dystonia. The LTD-like effect with PAS10 is also increased in focal dystonia but not in the target area of PAS. Depotentiation refers to the reversal of LTP by which LTP is abolished by a following procedure that has no effect when it is given alone. Brain-derived neurotrophic factor has a variety of roles in modulating both LTP and LTD. The Val66Met single nucleotide polymorphism is related to abnormal cortical plasticity. In this protocol, we propose a study to test the hypothesis that depotentiation is weaker in focal dystonia patients compared to healthy controls. In addition, motor cortical inhibition is decreased in focal dystonia. We will test the changes in motor cortical inhibition following different interventional procedures in focal dystonia. We will also test the relationship between depotentiation and LTP/LTD-like effects in focal dystonia patients.
Study population
We intend to study up to 20 patients with focal dystonia and 20 age-matched healthy volunteers. Subjects will complete up to 3 study visits involving 3 different interventional procedures. Various outcome measures will be performed during each study visit.
Design
This is a hypothesis-driven study. We will compare the depotentiation effect in patients with focal dystonia to that in healthy volunteers. Patients will be evaluated with a clinical rating scale during the screening visit. Three interventional procedures will be tested during three study visits. Specifically, PAS25-cTBS150 tests the primary hypothesis with a depotentiation effect. PAS25 tests LTP-like effect and PAS10 tests the LTD-like effect. We will investigate the difference in outcome measures between patients and healthy volunteers after the interventional procedures. We will perform genetic tests to identify the brain-derived neurotrophic factor genotype in the patients and healthy volunteers.
Outcome measures
The primary outcome measure is motor-evoked potential (MEP) induced by transcranial magnetic stimulation immediately after the interventional procedure of PAS25-cTBS150. We will compare MEP amplitude in patients with that in healthy volunteers to identify whether depotentiation is weaker in focal dystonia. The secondary outcome measures are MEP amplitudes at other time points after the PAS25-cTBS150 procedure. We will also perform exploratory studies to investigate the effects of interventional procedures of PAS25 and PAS10 alone. We will test the relationship between depotentiation and LTP/LTD-like effects in focal dystonia. We will also study other exploratory outcome measures such as: resting and active motor threshold, MEP recruitment curve, excitability of motor cortical circuits (short- and long-interval intracortical inhibition, and intracortical facilitation) after three different interventional procedures.
Study design
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Focal Dystonia | – | Other: PAS25, Other: PAS10, Other: PAS25-cTBS150Subjects diagnosed with Focal Dystonia |
| Healthy Volunteers | – | Other: PAS25, Other: PAS10, Other: PAS25-cTBS150Healthy Volunteers |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Subjects (patients and healthy volunteers) are recruited through the NIH Patient Recruitment and Public Liaison Office and from individuals who have participated in prior studies and are interested in being contacted for additional studies. Additionally, individuals who have contacted NIH to volunteer for research studies will be considered for recruitment.
Key inclusion criteria (13 listed)
- At least 18 years old.*
- Able to give informed consent.
- Able to comply with all study procedures.
- Abstain from alcohol for at least 48 hours prior to each study visit and caffeine on the day of the visit.
- Have no neurological or psychiatric disorders established by history and physical/neurological examination.
Key exclusion criteria (17 listed)
- Self-reported consumption of > 14 alcoholic drinks/week for a man and > 7 alcoholic drinks/week for a woman.
- Focal dystonia patients: presence of abnormal findings on neurological examination except for the diagnosis of focal dystonia. Healthy volunteers: no abnormal findings on neurological examination.
- History of or current brain tumor, stroke, head trauma with loss of consciousness, epilepsy or seizures.
- Have a Baclofen pump, or have neurostimulators for pain.
- Pregnant or breastfeeding women.
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 |
|---|---|---|
| PAS25We will record surface electromyography from the target abductor pollicis brevis muscle and adjacent first dorsal interosseous and abductor digiti minimi muscles. | Other | Focal Dystonia, Healthy Volunteers |
| PAS10We will record surface electromyography from the target abductor pollicis brevis muscle and adjacent first dorsal interosseous and abductor digiti minimi muscles. TBS is a special form of | Other | Focal Dystonia, Healthy Volunteers |
| PAS25-cTBS150We will record surface electromyography from the target abductor pollicis brevis muscle and adjacent first dorsal interosseous and abductor digiti minimi muscles. | Other | Focal Dystonia, Healthy Volunteers |
Primary outcome
MEP amplitude immediately after the PAS25-cTBS150 (depotentiation) protocol
Time frame: throughout
compare MEP amplitude in patients with that in healthy volunteers to identify whether depotentiation is weaker in focal dystonia
1 secondary outcome
MEP amplitudes
Time frame: throughout
Results and safety
The study was stopped early (reason given: PI leaving the NIH). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 May 2020.
- 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 Focal Dystonia 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 13 inclusion and 17 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: stopped early, as of the sponsor's last update on 6 May 2020. 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 was stopped early (reason given: PI leaving the NIH). Results are not available in the source record.
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 amplitude immediately after the PAS25-cTBS150 (depotentiation) protocol (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 6 May 2020.