StrokeNCT02188420
Finding an Optimal Latency for Paired Associative Stimulation in People With Chronic Stroke
A study testing Transcranial Magnetic Stimulation will be applied to the primary motor cortex at the interstimulus interval of ("Latency" - 3ms), Transcranial Magnetic Stimulation will be applied to the primary motor cortex at the interstimulus interval of ("Latency" - 5ms) and ranscranial Magnetic Stimulation will be applied to the primary motor cortex at the interstimulus interval of ("Latency" - 7ms) in people with Stroke, run by University of Minnesota at 1 site in United States.
Trial summary
After a stroke, there is an exaggerated inhibitory influence from the non-stroke hemisphere to the stroke hemisphere. Brain stimulation using repetitive transcranial magnetic stimulation (rTMS) to the non-stroke hemisphere can decrease this inhibition. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Stroke
- What is being tested?
- Transcranial Magnetic Stimulation will be applied to the primary motor cortex at the interstimulus interval of ("Latency" - 3ms), Transcranial Magnetic Stimulation will be applied to the primary motor cortex at the interstimulus interval of ("Latency" - 5ms) and ranscranial Magnetic Stimulation will be applied to the primary motor cortex at the interstimulus interval of ("Latency" - 7ms)
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 4 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2014to Dec 2016
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- stroke (ischemic or hemorrhagic) of greater than 6 months duration
- impairment in the paretic hand
- over 18 years old
- male or female
- on mini mental status exam must have score of 22 or higher
- must have elicitable motor evoked potential (MEP)
Who cannot join
- seizure within the past two years
- receptive aphasia
- epileptogenic medication
- major psychiatric disorder
- other interfering comorbidities
- pregnancy
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Minnesota Clinical and Translational Science Institute
Minneapolis, Minnesota, 55414
About this study
Official title: Effect of Different Interpulse Intervals of Paired Associative Stimulation on Cortical Excitability in People With Chronic Stroke
After a stroke, there is an exaggerated inhibitory influence from the non-stroke hemisphere to the stroke hemisphere. Brain stimulation using repetitive transcranial magnetic stimulation (rTMS) to the non-stroke hemisphere can decrease this inhibition. Paired Associative Stimulation (PAS) may be a more effective way to produce this same inhibition, as shown in healthy subjects. However, it is not known whether this will translate to people with stroke. PAS consists of a peripheral nerve stimulus paired a short time later with a cortical stimulus to change the excitability within the brain. Thus the investigators will apply PAS to people with stroke, but the investigators need to first determine the most effective interpulse interval (IPI) between the peripheral and cortical stimuli. Our research question is which of three different IPIs is most effective in changing the excitability of the brain.
The purpose of this study is to determine the optimal IPI between a peripheral nerve pulse and a cortical stimulus that will be most effective in changing excitability of the brain in people with chronic stroke. The investigators hypothesize that the cortical excitability of the nonstroke hemisphere will be most inhibited with the latency-5ms condition.
Read the detailed description
Numerous PAS studies have been done in healthy subjects and all have been done safely. The proper interpulse interval in healthy individuals between the peripheral nerve stimulus and the cortical stimulus is known to be "latency-5ms." However, this may be different in individuals with stroke.
Specific Aim: what is the optimal interpulse interval to achieve the maximum inhibitory effect in the nonstroke hemisphere?
We will recruit three subjects with chronic stroke. Electroencephalography (EEG) will be used to determine the latency between the peripheral nerve stimulus and the sensory evoked potential in each subject. We will then assess the following IPIs on each subject in a random order: "latency" - 3ms, -5ms and -7ms. There will be a fourth condition of "latency" + 100ms (known to have no effect) to be used as a control. The washout period will be at least one week between each of these conditions.
The optimal IPI will be determined from these tests by comparing single pulse transcranial magnetic stimulation (TMS) measures for cortical excitability. Prior to each treatment, each subject will receive 20 single pulse cortical stimuli to serve as pretest data. The post tests for each condition will consist of 20 single pulse cortical stimuli at 0, 5, 10, 15, 30, 45 and 60 minutes after the PAS condition. Data analysis will consist of a single-subject analysis with the two standard deviation bandwidth method of each post-test compared to pre-test.
We hypothesize that there will be no adverse advents and that this optimal IPI will be "latency"-5ms.
- Conditions
- Stroke
- Being tested
- Transcranial Magnetic Stimulation will be applied to the primary motor cortex at the interstimulus interval of ("Latency" - 3ms), Transcranial Magnetic Stimulation will be applied to the primary motor cortex at the interstimulus interval of ("Latency" - 5ms), ranscranial Magnetic Stimulation will be applied to the primary motor cortex at the interstimulus interval of ("Latency" - 7ms), Transcranial Magnetic Stimulation Time 100ms
- Keywords
- PAS, TMS, Stroke, Paired Associative Stimulation, Transcranial Magnetic Stimulation
- Medical subject headings
- Stroke
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Transcranial Magnetic Stimulation will be applied to the primary motor cortex at the interstimulus interval of ("Latency" - 3ms)Device
Also called TMS, Magstim
Transcranial Magnetic Stimulation will be applied to the primary motor cortex at the interstimulus interval of ("Latency" - 3ms) where "latency" refers to the amount of time for the arrival of a sensory evoked potential as determined by EEG.
Transcranial Magnetic Stimulation will be applied to the primary motor cortex at the interstimulus interval of ("Latency" - 5ms)Device
Also called TMS
Transcranial Magnetic Stimulation 5ms
ranscranial Magnetic Stimulation will be applied to the primary motor cortex at the interstimulus interval of ("Latency" - 7ms)Device
Also called TMS
Transcranial Magnetic Stimulation 7ms
Transcranial Magnetic Stimulation Time 100msDevice
Also called TMS
Active Compator
| Study group | Role | What they receive |
|---|---|---|
| N20-3ms, N20-5ms, N20+100ms, N20-7ms | Experimental | Transcranial Magnetic Stimulation will be applied to the primary motor cortex at the interstimulus interval of ("Latency" - 3ms) where "latency" refers to the amount of time for the arrival of a sensory evoked potential as determined by EEG. Wash out period of 1 week then next level will be applied Receives: Device: Transcranial Magnetic Stimulation will be applied to the primary motor cortex at the interstimulus interval of ("Latency" - 3ms) |
| N20-5ms, N20-3ms, N20-7ms, N20+100ms | Experimental | Transcranial Magnetic Stimulation will be applied to the primary motor cortex at the interstimulus interval of ("Latency" - 5ms) where "latency" refers to the amount of time for the arrival of a sensory evoked potential as determined by EEG. Wash out period of 1 week then next level will be applied
Latency minus 7ms Wash out period of 1 week Latency plus 100ms Active comparator Receives: Device: Transcranial Magnetic Stimulation will be applied to the primary motor cortex at the interstimulus interval of ("Latency" - 5ms) |
| N20-7ms, N20-5ms, N20-3ms,N20+100ms | Experimental | Transcranial Magnetic Stimulation will be applied to the primary motor cortex at the interstimulus interval of ("Latency" - 7ms) where "latency" refers to the amount of time for the arrival of a sensory evoked potential as determined by EEG. Wash out period of 1 week then next level will be applied Receives: Device: ranscranial Magnetic Stimulation will be applied to the primary motor cortex at the interstimulus interval of ("Latency" - 7ms) |
| N20-3ms, N20+100ms, N20-5ms, N20-7ms | Active comparator | Transcranial Magnetic Stimulation will be applied to the primary motor cortex at the interstimulus interval of ("Latency" - 100ms) where "latency" refers to the amount of time for the arrival of a sensory evoked potential as determined by EEG. Wash out period of 1 week Receives: Device: Transcranial Magnetic Stimulation Time 100ms |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Cortical Excitability Using Single TMS Pulses
Assess average size of 20 motor evoked potentials via electromyography (EMG) signal resulting from single TMS pulses to the motor cortex. Measurements taken before and after paired associative stimulation treatment at each session.
Measured: Change from pretest (immediately prior to PAS application) to posttest which will occur over the 60 minutes that follow PAS application.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jul 2014 (estimated)
- Study startSep 2014
- Primary completionMay 2015
- Study completionDec 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for StrokeStudies of the same condition, open and under way.
- More trials run by University of MinnesotaThe 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Device feasibility
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 4 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Minnesota
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Kate Frost, MS, Principal investigator, University of Minnesota
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02188420
- Sponsor's protocol ID
- 1406M51743
- Status last verified
- Feb 2025
- First submitted
- 30 Jun 2014
- Last updated
- 6 Feb 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 6 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Different Interpulse Intervals of Paired Associative Stimulation on Cortical Excitability in People With Chronic Stroke
- ClinicalTrials.gov ID
- NCT02188420
- Acronym / sponsor ID
- 1406M51743
- Conditions
- Stroke
- Keywords
- PAS, TMS, Stroke, Paired Associative Stimulation, Transcranial Magnetic Stimulation
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 4 participants (actual)
- Lead sponsor
- University of MinnesotaUniversity, hospital or other
- Study start
- Sep 2014
- Primary completion
- May 2015 (actual)
- Study completion
- Dec 2016 (actual)
- First posted
- 11 Jul 2014 (estimated)
- Results
- Posted 6 Feb 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
After a stroke, there is an exaggerated inhibitory influence from the non-stroke hemisphere to the stroke hemisphere. Brain stimulation using repetitive transcranial magnetic stimulation (rTMS) to the non-stroke hemisphere can decrease this inhibition. Paired Associative Stimulation (PAS) may be a more effective way to produce this same inhibition, as shown in healthy subjects. However, it is not known whether this will translate to people with stroke. PAS consists of a peripheral nerve stimulus paired a short time later with a cortical stimulus to change the excitability within the brain. Thus the investigators will apply PAS to people with stroke, but the investigators need to first determine the most effective interpulse interval (IPI) between the peripheral and cortical stimuli. Our research question is which of three different IPIs is most effective in changing the excitability of the brain.
The purpose of this study is to determine the optimal IPI between a peripheral nerve pulse and a cortical stimulus that will be most effective in changing excitability of the brain in people with chronic stroke. The investigators hypothesize that the cortical excitability of the nonstroke hemisphere will be most inhibited with the latency-5ms condition.
Detailed description
Numerous PAS studies have been done in healthy subjects and all have been done safely. The proper interpulse interval in healthy individuals between the peripheral nerve stimulus and the cortical stimulus is known to be "latency-5ms." However, this may be different in individuals with stroke.
Specific Aim: what is the optimal interpulse interval to achieve the maximum inhibitory effect in the nonstroke hemisphere?
We will recruit three subjects with chronic stroke. Electroencephalography (EEG) will be used to determine the latency between the peripheral nerve stimulus and the sensory evoked potential in each subject. We will then assess the following IPIs on each subject in a random order: "latency" - 3ms, -5ms and -7ms. There will be a fourth condition of "latency" + 100ms (known to have no effect) to be used as a control. The washout period will be at least one week between each of these conditions.
The optimal IPI will be determined from these tests by comparing single pulse transcranial magnetic stimulation (TMS) measures for cortical excitability. Prior to each treatment, each subject will receive 20 single pulse cortical stimuli to serve as pretest data. The post tests for each condition will consist of 20 single pulse cortical stimuli at 0, 5, 10, 15, 30, 45 and 60 minutes after the PAS condition. Data analysis will consist of a single-subject analysis with the two standard deviation bandwidth method of each post-test compared to pre-test.
We hypothesize that there will be no adverse advents and that this optimal IPI will be "latency"-5ms.
Study design
- Primary purpose
- Device feasibility
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind (participant)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| N20-3ms, N20-5ms, N20+100ms, N20-7ms | Experimental | Device: Transcranial Magnetic Stimulation will be applied to the primary motor cortex at the interstimulus interval of ("Latency" - 3ms)Transcranial Magnetic Stimulation will be applied to the primary motor cortex at the interstimulus interval of ("Latency" - 3ms) where "latency" refers to the amount of time for the arrival of a sensory evoked potential as determined by EEG. Wash out period of 1 week then next level will be applied |
| N20-5ms, N20-3ms, N20-7ms, N20+100ms | Experimental | Device: Transcranial Magnetic Stimulation will be applied to the primary motor cortex at the interstimulus interval of ("Latency" - 5ms)Transcranial Magnetic Stimulation will be applied to the primary motor cortex at the interstimulus interval of ("Latency" - 5ms) where "latency" refers to the amount of time for the arrival of a sensory evoked potential as determined by EEG. Wash out period of 1 week then next level will be applied Latency minus 7ms Wash out period of 1 week Latency plus 100ms Active comparator |
| N20-7ms, N20-5ms, N20-3ms,N20+100ms | Experimental | Device: ranscranial Magnetic Stimulation will be applied to the primary motor cortex at the interstimulus interval of ("Latency" - 7ms)Transcranial Magnetic Stimulation will be applied to the primary motor cortex at the interstimulus interval of ("Latency" - 7ms) where "latency" refers to the amount of time for the arrival of a sensory evoked potential as determined by EEG. Wash out period of 1 week then next level will be applied |
| N20-3ms, N20+100ms, N20-5ms, N20-7ms | Active comparator | Device: Transcranial Magnetic Stimulation Time 100msTranscranial Magnetic Stimulation will be applied to the primary motor cortex at the interstimulus interval of ("Latency" - 100ms) where "latency" refers to the amount of time for the arrival of a sensory evoked potential as determined by EEG. Wash out period of 1 week |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- stroke (ischemic or hemorrhagic) of greater than 6 months duration
- impairment in the paretic hand
- over 18 years old
- male or female
- on mini mental status exam must have score of 22 or higher
Key exclusion criteria (6 listed)
- seizure within the past two years
- receptive aphasia
- epileptogenic medication
- major psychiatric disorder
- other interfering comorbidities
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 |
|---|---|---|
| Transcranial Magnetic Stimulation will be applied to the primary motor cortex at the interstimulus interval of ("Latency" - 3ms)Also: TMS, MagstimTranscranial Magnetic Stimulation will be applied to the primary motor cortex at the interstimulus interval of ("Latency" - 3ms) where "latency" refers to the amount of time for the arrival of a sensory evoked potential as determined by EEG. | Device | N20-3ms, N20-5ms, N20+100ms, N20-7ms |
| Transcranial Magnetic Stimulation will be applied to the primary motor cortex at the interstimulus interval of ("Latency" - 5ms)Also: TMSTranscranial Magnetic Stimulation 5ms | Device | N20-5ms, N20-3ms, N20-7ms, N20+100ms |
| ranscranial Magnetic Stimulation will be applied to the primary motor cortex at the interstimulus interval of ("Latency" - 7ms)Also: TMSTranscranial Magnetic Stimulation 7ms | Device | N20-7ms, N20-5ms, N20-3ms,N20+100ms |
| Transcranial Magnetic Stimulation Time 100msAlso: TMSActive Compator | Device | N20-3ms, N20+100ms, N20-5ms, N20-7ms |
Primary outcome
Change in Cortical Excitability Using Single TMS Pulses
Time frame: Change from pretest (immediately prior to PAS application) to posttest which will occur over the 60 minutes that follow PAS application.
Assess average size of 20 motor evoked potentials via electromyography (EMG) signal resulting from single TMS pulses to the motor cortex. Measurements taken before and after paired associative stimulation treatment at each session.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Feb 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Web-Based Tele-Rehabilitation Using Action Observation and Mirror Therapy for Subacute Stroke: A Randomized Controlled Trial
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Early Motor-Cognitive Integrative Training on Cognitive and Motor Performance in Patients With Aneurysmal Subarachnoid Hemorrhage
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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.
Kate Frost, MS principal investigator
University of Minnesota
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Transcranial Magnetic Stimulation will be applied to the primary motor cortex at the interstimulus interval of ("Latency" - 3ms), Transcranial Magnetic Stimulation will be applied to the primary motor cortex at the interstimulus interval of ("Latency" - 5ms) and ranscranial Magnetic Stimulation will be applied to the primary motor cortex at the interstimulus interval of ("Latency" - 7ms) in people with Stroke, run by University of Minnesota 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 6 inclusion and 6 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 6 Feb 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.
Are results available for this study?
Yes. Results are posted in the registry (first posted 6 Feb 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Change in Cortical Excitability Using Single TMS Pulses (time frame: Change from pretest (immediately prior to PAS application) to posttest which will occur over the 60 minutes that follow PAS application.). 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 Feb 2025.