StrokeNCT00366184
Influence of Theta Burst Stimulation and Carbidopa-Levodopa on Motor Performance in Stroke Patients
An observational study of Stroke, run by National Institute of Neurological Disorders and Stroke (NINDS) at 1 site in United States.
Trial 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 patient's scalp. Read more about this study
- Who is it for?
- Ages 18 to 90 years
- Conditions the study is for
- Stroke
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- 8 Aug 2006to 26 May 2010
- 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 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- PATIENTS:
- Age 18 - 90
- Ischemic cerebral infarction more than 6 months prior to testing not involving cortical motor areas
- Initial severe paresis (MRC Grade 2 or less in hand muscles) with considerable motor recovery
- Ability to make ballistic thumb abduction or wrist extension movements in the affected hand
- HEALTHY SUBJECTS:
Show all 9Show fewer
- Age 18 - 90
- Right handed
- Able to concentrate and to perform the tasks required
Who cannot join
- PATIENTS:
- More than one ischemic stroke, or any hemorrhagic stroke
- Large cortical stroke
- Significant cognitive impairment, defined as a Mini Mental State Examination score of 23 or less
- History of seizures or other neurological illness (except stroke)
- History of alcohol or drug abuse
Show all 20Show fewer
- Inability to make necessary thumb abduction or wrist extension movements
- Current or recent use of neuroleptic medication, tricyclic anti-depressants or monoamine oxidase inhibitors
- History of narrow angle glaucoma
- Contraindications to TMS - presence of cardiac pacemaker, intracardiac lines, implanted pumps or stimulators, or metal objects inside the eye or skull
- Pregnancy (as the effects of TBS on the fetus are as yet unknown)
- Uncontrolled medical (e.g. cardiovascular disease expressed as uncontrolled arrhythmias, shortness of breath, or overt signs of severe peripheral edema at the initial neurological exam, severe rheumatoid arthritis, arthritic joint deformity, active cancer or renal disease), or psychiatric problems (defined as having received medical treatment from a psychiatrist).
- HEALTHY SUBJECTS:
- Contraindications to TMS (as above)
- Pregnancy (see above)
- History of seizures or other neurological illness
- History of alcohol or drug abuse
- History of depression / psychiatric illness requiring use of anti-psychotic drugs or anti-depressants
- Current or recent use of neuroleptic medication, tricyclic anti-depressants or monoamine oxidase inhibitors
- History of narrow angle glaucoma
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: Influencing Motor Performance in Patients With Stroke by Combined Theta Burst Stimulation and Carbidopa-Levodopa
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 patient's 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 Parkinson's 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.
Read more
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.
Read the 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 TBS/sham and Carbidopa-Levodopa/placebo. 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-Levodopa/placebo, 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 Investigator's 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.
- Conditions
- Stroke
- Keywords
- Neuromodulation, Stroke, Motor Cortex, Motor Learning, L-Dopa, Transcranial Magnetic Stimulation, Levodopa, Healthy Volunteer, HV
- Medical subject headings
- Stroke
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Aug 2006 (estimated)
- Study start8 Aug 2006
- Study completion26 May 2010
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 StrokeStudies 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
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00366184
- Sponsor's protocol ID
- 060225
- Other IDs
- 06-N-0225
- Status last verified
- 26 May 2010
- First submitted
- 17 Aug 2006
- Last updated
- 2 Jul 2017
- Results posted
- No
Publications
Conforto AB, Kaelin-Lang A, Cohen LG. Increase in hand muscle strength of stroke patients after somatosensory stimulation. Ann Neurol. 2002 Jan;51(1):122-5. doi: 10.1002/ana.10070.
PubMed 11782992Di Lazzaro V, Pilato F, Saturno E, Oliviero A, Dileone M, Mazzone P, Insola A, Tonali PA, Ranieri F, Huang YZ, Rothwell JC. Theta-burst repetitive transcranial magnetic stimulation suppresses specific excitatory circuits in the human motor cortex. J Physiol. 2005 Jun 15;565(Pt 3):945-50. doi: 10.1113/jphysiol.2005.087288. Epub 2005 Apr 21.
PubMed 15845575Donoghue JP. Plasticity of adult sensorimotor representations. Curr Opin Neurobiol. 1995 Dec;5(6):749-54. doi: 10.1016/0959-4388(95)80102-2.
PubMed 8805413
Study at a glance
From the registry record, last updated by the sponsor on 2 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Influencing Motor Performance in Patients With Stroke by Combined Theta Burst Stimulation and Carbidopa-Levodopa
- ClinicalTrials.gov ID
- NCT00366184
- Acronym / sponsor ID
- 060225
- Conditions
- Stroke
- Keywords
- Neuromodulation, Stroke, Motor Cortex, Motor Learning, L-Dopa, Transcranial Magnetic Stimulation, Levodopa, Healthy Volunteer
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- National Institute of Neurological Disorders and Stroke (NINDS)US National Institutes of Health
- Study start
- 8 Aug 2006
- Study completion
- 26 May 2010
- First posted
- 21 Aug 2006 (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.
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 patient's 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 Parkinson's 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.
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 TBS/sham and Carbidopa-Levodopa/placebo. 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-Levodopa/placebo, 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 Investigator's 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 design
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Age 18 - 90
- Ischemic cerebral infarction more than 6 months prior to testing not involving cortical motor areas
- Initial severe paresis (MRC Grade 2 or less in hand muscles) with considerable motor recovery
- Ability to make ballistic thumb abduction or wrist extension movements in the affected hand
- Age 18 - 90
Key exclusion criteria (20 listed)
- More than one ischemic stroke, or any hemorrhagic stroke
- Large cortical stroke
- Significant cognitive impairment, defined as a Mini Mental State Examination score of 23 or less
- History of seizures or other neurological illness (except stroke)
- History of alcohol or drug abuse
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
Not reported in the source record.
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 2 Jul 2017.
- Background: PubMed 11782992Conforto AB, Kaelin-Lang A, Cohen LG. Increase in hand muscle strength of stroke patients after somatosensory stimulation. Ann Neurol. 2002 Jan;51(1):122-5. doi: 10.1002/ana.10070.
- Background: PubMed 15845575Di Lazzaro V, Pilato F, Saturno E, Oliviero A, Dileone M, Mazzone P, Insola A, Tonali PA, Ranieri F, Huang YZ, Rothwell JC. Theta-burst repetitive transcranial magnetic stimulation suppresses specific excitatory circuits in the human motor cortex. J Physiol. 2005 Jun 15;565(Pt 3):945-50. doi: 10.1113/jphysiol.2005.087288. Epub 2005 Apr 21.
- Background: PubMed 8805413Donoghue JP. Plasticity of adult sensorimotor representations. Curr Opin Neurobiol. 1995 Dec;5(6):749-54. doi: 10.1016/0959-4388(95)80102-2.
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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.
The record lists no contact. Use the official record to reach the sponsor.
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 Stroke, 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 9 inclusion and 20 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 2 Jul 2017. 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.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00366184, 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 2 Jul 2017.