Ignite Creation Date:
2024-05-05 @ 5:01 PM
Last Modification Date:
2024-10-26 @ 9:27 AM
Study NCT ID:
NCT00366184
Status:
COMPLETED
Last Update Posted:
2017-07-02
First Post:
2006-08-17
Brief Title:
Influence of Theta Burst Stimulation and Carbidopa-Levodopa on Motor Performance in Stroke Patients
Sponsor:
National Institute of Neurological Disorders and Stroke NINDS
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Influencing Motor Performance in Patients With Stroke by Combined Theta Burst Stimulation and Carbidopa-Levodopa
Status:
COMPLETED
Status Verified Date:
2010-05-26
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This study will examine whether transcranial magnetic stimulation TMS of the brain used in combination with carbidopa-levodopa is more effective in temporarily improving the speed of hand movement in stoke patients than TMS alone In TMS a wire coil is held on the patients scalp A brief electrical current is passed through the coil creating a magnetic pulse that stimulates the brain The effect of TMS on the muscles is detected with small metal disk electrodes taped to the skin of the arms or legs Carbidopa-levodopa is a medication usually used to treat Parkinsons disease but it may improve the effect of theta burst stimulation
Two kinds of TMS are used in this study In single-pulse TMS one or two pulses are delivered at a time in order to measure brain activity at that moment In repetitive TMS rTMS a series of pulses are given in short bursts temporarily altering brain activity The type of rTMS used in this study is called theta burst stimulation
Healthy normal volunteers and people who had a stroke 6 months or more before entering the study may be eligible to participate All candidates must be between 18 and 90 years of age Stroke patients must have had significant hand weakness and made a moderate or good recovery and must be able to move either the thumb or the wrist on the affected hand reasonably well Normal volunteers must be right-handed
Participants complete the testing for this study in four main sessions scheduled at least a week apart and five short follow-up sessions At each main session participants take either a carbidopa-levodopa tablet or a placebo a look-alike inactive substance Stroke patients have their arm and hand function assessed using two tests One requires them to insert pegs into holes the other includes writing lifting various objects and performing activities like turning pages feeding or stacking checkers
All subjects complete a questionnaire regarding their mood and alertness and then perform tests of thumb or wrist movement For this test a small electrical stimulus is applied to the side of the hand and the subject must respond to the stimulus as quickly as possible by making a thumb or wrist movement This is repeated several times over about 3 minutes A second test follows in which the subject moves the thumb or wrist in response to a beep from a speaker This test is repeated several times over about 8 minutes Some measurements are taken using single-pulse TMS during the beginning middle and end of this test In two of the four sessions theta burst stimulation is applied after the single-pulse TMS and in the other two sessions sham theta burst stimulation is applied
Five follow-up sessions are scheduled one day after each main session and one week following the final one In these sessions subjects perform an abbreviated form of the thumb movement tests
Two kinds of TMS are used in this study In single-pulse TMS one or two pulses are delivered at a time in order to measure brain activity at that moment In repetitive TMS rTMS a series of pulses are given in short bursts temporarily altering brain activity The type of rTMS used in this study is called theta burst stimulation
Healthy normal volunteers and people who had a stroke 6 months or more before entering the study may be eligible to participate All candidates must be between 18 and 90 years of age Stroke patients must have had significant hand weakness and made a moderate or good recovery and must be able to move either the thumb or the wrist on the affected hand reasonably well Normal volunteers must be right-handed
Participants complete the testing for this study in four main sessions scheduled at least a week apart and five short follow-up sessions At each main session participants take either a carbidopa-levodopa tablet or a placebo a look-alike inactive substance Stroke patients have their arm and hand function assessed using two tests One requires them to insert pegs into holes the other includes writing lifting various objects and performing activities like turning pages feeding or stacking checkers
All subjects complete a questionnaire regarding their mood and alertness and then perform tests of thumb or wrist movement For this test a small electrical stimulus is applied to the side of the hand and the subject must respond to the stimulus as quickly as possible by making a thumb or wrist movement This is repeated several times over about 3 minutes A second test follows in which the subject moves the thumb or wrist in response to a beep from a speaker This test is repeated several times over about 8 minutes Some measurements are taken using single-pulse TMS during the beginning middle and end of this test In two of the four sessions theta burst stimulation is applied after the single-pulse TMS and in the other two sessions sham theta burst stimulation is applied
Five follow-up sessions are scheduled one day after each main session and one week following the final one In these sessions subjects perform an abbreviated form of the thumb movement tests
Detailed Description:
OBJECTIVE
Theta Burst Stimulation TBS is a type of sub-threshold repetitive Transcranial Magnetic Stimulation rTMS which has effects on the excitability of human motor cortex that outlast stimulation by up to an hour TBS also affects performance of a motor task for up to 30 minutes after stimulation in healthy subjects and improves reaction times and increases corticospinal excitability in patients with chronic stroke Talelli 2005 The advantages of TBS over other non-invasive brain stimulation strategies are its low intensity short duration of application and long lasting effects
The spectrum of behavioral effects investigated is so far modest Evidence is accumulating that dopaminergic agents enhance synaptic plasticity Otani 1998 and improve motor training in healthy humans Meintzchel 2005 After stroke Carbidopa-Levodopa has also enhanced the response to physiotherapy and motor learning Scheidtmann 2001 Floel 2005 This protocol aims to test the hypothesis that Carbidopa-Levodopa may enhance the beneficial effect of TBS on reaction times in patients with chronic stroke
STUDY POPULATION
We plan to investigate 18 patients with motor impairment more than 6 months after ischemic stroke and 10 healthy volunteers Approval is sought for a total of 28 patients and 30 healthy volunteers to account for possible dropouts and pilot experiments described below
DESIGN
Each subject will be asked to participate in 4 sessions at least a week apart The experiment will test simple reaction times in the thumb or wrist of the paretic hand before and 7 minutes after either genuine or sham TBS This will be followed by a measure of motor learning using a well-characterized paradigm Muellbacher 2001 which involves optimizing an externally paced ballistic thumb or wrist movement and TMS measurement of corticospinal excitability Performance of the learned task will be further assessed and TMS measures made at 2 hours 1 day and 1 week following the training session The experimental design for the four sessions will be 2x2 with TBSsham and Carbidopa-Levodopaplacebo For TBS the patient will be given 3 minutes of either genuine or sham TBS to the hand representation of the motor cortex Huang 2005 For Carbidopa-Levodopaplacebo identical preparations from the NIH pharmacy will be given 1 hour beforehand TBS has previously been used in 72 healthy subjects 7 studies in Europe and in 10 patients with chronic stroke 2 studies in the Lead Associate Investigators lab in London No side effects or seizures have been reported Ten normal volunteers will be studied first to optimize experimental settings
OUTCOME MEASURES
The primary outcome measure will be reaction times Improvement in peak acceleration in the learning task will constitute a secondary measure We expect to see improved reaction times with genuine TBS vs sham and will look for an interaction whereby Carbidopa-Levodopa may enhance this effect vs placebo This would suggest that synergy between dopaminergic modulation and TBS may show promise to produce clinical gains after stroke
Theta Burst Stimulation TBS is a type of sub-threshold repetitive Transcranial Magnetic Stimulation rTMS which has effects on the excitability of human motor cortex that outlast stimulation by up to an hour TBS also affects performance of a motor task for up to 30 minutes after stimulation in healthy subjects and improves reaction times and increases corticospinal excitability in patients with chronic stroke Talelli 2005 The advantages of TBS over other non-invasive brain stimulation strategies are its low intensity short duration of application and long lasting effects
The spectrum of behavioral effects investigated is so far modest Evidence is accumulating that dopaminergic agents enhance synaptic plasticity Otani 1998 and improve motor training in healthy humans Meintzchel 2005 After stroke Carbidopa-Levodopa has also enhanced the response to physiotherapy and motor learning Scheidtmann 2001 Floel 2005 This protocol aims to test the hypothesis that Carbidopa-Levodopa may enhance the beneficial effect of TBS on reaction times in patients with chronic stroke
STUDY POPULATION
We plan to investigate 18 patients with motor impairment more than 6 months after ischemic stroke and 10 healthy volunteers Approval is sought for a total of 28 patients and 30 healthy volunteers to account for possible dropouts and pilot experiments described below
DESIGN
Each subject will be asked to participate in 4 sessions at least a week apart The experiment will test simple reaction times in the thumb or wrist of the paretic hand before and 7 minutes after either genuine or sham TBS This will be followed by a measure of motor learning using a well-characterized paradigm Muellbacher 2001 which involves optimizing an externally paced ballistic thumb or wrist movement and TMS measurement of corticospinal excitability Performance of the learned task will be further assessed and TMS measures made at 2 hours 1 day and 1 week following the training session The experimental design for the four sessions will be 2x2 with TBSsham and Carbidopa-Levodopaplacebo For TBS the patient will be given 3 minutes of either genuine or sham TBS to the hand representation of the motor cortex Huang 2005 For Carbidopa-Levodopaplacebo identical preparations from the NIH pharmacy will be given 1 hour beforehand TBS has previously been used in 72 healthy subjects 7 studies in Europe and in 10 patients with chronic stroke 2 studies in the Lead Associate Investigators lab in London No side effects or seizures have been reported Ten normal volunteers will be studied first to optimize experimental settings
OUTCOME MEASURES
The primary outcome measure will be reaction times Improvement in peak acceleration in the learning task will constitute a secondary measure We expect to see improved reaction times with genuine TBS vs sham and will look for an interaction whereby Carbidopa-Levodopa may enhance this effect vs placebo This would suggest that synergy between dopaminergic modulation and TBS may show promise to produce clinical gains after stroke
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
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 |
|---|---|---|---|
| 06-N-0225 | None | None | None |