Ignite Creation Date:
2024-05-06 @ 10:16 AM
Last Modification Date:
2024-10-26 @ 12:27 PM
Study NCT ID:
NCT03206112
Status:
TERMINATED
Last Update Posted:
2020-05-06
First Post:
2017-06-30
Brief Title:
Loss of Depotentiation in Focal Dystonia
Sponsor:
National Institute of Neurological Disorders and Stroke NINDS
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Loss of Depotentiation in Focal Dystonia
Status:
TERMINATED
Status Verified Date:
2020-04
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
PI leaving the NIH
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief 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 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
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 LTPLTD-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 LTPLTD-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
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 LTPLTD-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 LTPLTD-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 Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 17-N-0123 | None | None | None |