StrokeNCT02867670
TMS as a Biological Marker of Neuroplasticity
An observational study of Stroke and Aphasia, run by University of Pennsylvania at 1 site in United States.
Trial summary
TMS is a non-invasive brain stimulation technique, which can be used to change the activity of a person's brain cells without needles or surgery. In this study, the invesigators are interested in the brain's ability to adapt (also called "neuroplasticity") and regain language functioning after a stroke-specifically… Read more about this study
- Who is it for?
- Ages 18 to 80 years
- What is being tested?
- Transcranial Magnetic Stimulation
- Type of treatment
- Medical device
- How many people
- 41 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2013to Jun 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 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Individuals who have had one or more strokes and are now experiencing the symptoms of aphasia. Aphasia is a communication disorder which may result in difficulties speaking,understanding speech, or both.
Who may be able to join
- Must have Aphasia due to stroke
- Stroke must have occurred at least 6 months ago
- Native English speaker
- Willing \& able to have a MRI
Who cannot join
- Disorders of the brain other than stroke (i.e. tumor, Parkinsons, cancer... etc.)
- History of seizures/ or epilepsy
- Pacemaker or other implanted electronic devices
- Consumption of medications that lower seizure threshold
- History of psychiatric disorders
- History of tinnitus
- Current abuse of drugs or alcohol
- Pregnant or plan to get pregnant
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
About this study
TMS is a non-invasive brain stimulation technique, which can be used to change the activity of a person's brain cells without needles or surgery. In this study, the invesigators are interested in the brain's ability to adapt (also called "neuroplasticity") and regain language functioning after a stroke-specifically, they want to determine whether how a person's brain responds to TMS in the short term can be used to predict how well they will recover language abilities in the long term.
Read the detailed description
Aphasia is an impairment of language that may occur after a stroke (or other brain injuries). A person with aphasia may experience difficulties speaking, understanding speech, reading, writing, or any combination of these symptoms. Despite advances in understanding of language systems and functional neuroplasticity after brain injury, accurate predictors of aphasia recovery after stroke remain elusive. In order to better understand, predict, and enhance language improvement after stroke, there is a critical need to develop tools that can assess the influence of neuroplasticity on recovery.
Transcranial magnetic stimulation (TMS) is a non-invasive brain stimulation tool that has been used to predict the brain's neuroplastic capacity by assessing physiological responses observed immediately following administration of TMS. Additionally, difference in the physiological response to TMS have been shown to be affected by polymorphism in the gene coding for brain derived neurotrophic factor (BDNF). The current project explores the idea that because neural mechanisms of plasticity are essential determinants of both recovery after brain injury and physiologic response to TMS, magnetic brain stimulation could be employed as an indicator of the capacity for clinically relevant neuroplasticity, and potentially as a predictor of recovery from post-stroke deficits such as aphasia
The goals of this protocol are to 1) explore the utility of theta burst stimulation (TBS), a type of transcranial magnetic stimulation (TMS), as a tool for assessing neuroplasticity in the language system in patients with aphasia due to stroke, 2) and to assess the utility of TBS as a biomarker and predictor of functional recovery in patients with aphasia.
This protocol will encompass two separate but related experiments. In the first experiment, the investigators will apply TBS to brain regions that control language functions in aphasic patients in order to determine whether we can induce a transient improvement in naming ability. They will use a statistical model they have developed to categorize patients as either having High Plasticity or Low Plasticity. The investigators will determine whether this distinction predicts which patients are likely to have greater TBS-induced changes in language performance. In the second experiment, in the same patients, the investigators will apply TBS to the motor cortex to elicit changes in motor evoked potentials (MEPs). Using the same model to form matched groups, we predict that MEPs will be more attenuated in High Plasticity groups compared to the Low Plasticity group.
- Being tested
- Transcranial Magnetic Stimulation
- Keywords
- Transcranial Magnetic Stimulation (TMS)
- Medical subject headings
- Stroke, Aphasia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Transcranial Magnetic StimulationDevice
Also called TMS
TMS is a form of non-invasive brain stimulation which uses magnetic pulses to stimulate regions of the brain from outside the head, on the scalp. Specifically, TMS is performed with a copper-and-plastic coil that emits a magnetic field, which can affect brain cells in specific locations. In this study, researchers will also use a form of TMS called theta-burst stimulation (TBS), where TMS pulses are delivered rapidly over time.
| Study group | Role | What they receive |
|---|---|---|
| Transcranial Magnetic Stimulation of Motor Cortex | All study participants will receive real TMS stimulation over the primary motor cortex in order to collect physiological measures which will later be correlated with measures of neuroplasticity. There is NO placebo stimulation. Receives: Device: Transcranial Magnetic Stimulation | |
| Transcranial Magnetic Stimulation of Language Cortex | All study participants will receive real TMS stimulation over the language cortex and a control site (i.e. vertex). Transient changes in speech production will be recorded and compared to measures of neuroplasticity. There is NO placebo stimulation. Receives: Device: Transcranial Magnetic Stimulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Transient TBS-induced changes in motor evoked potentials (MEPs)
Single-Pulse TMS will be used to measure MEPs prior to and after stimulation. When measuring MEPs, single pulses of TMS will be administered at approximately 120% of motor threshold, and with a minimum interstimulus interval of 5 seconds. Mean MEP amplitudes will be calculated by averaging the MEP amplitudes generated by 20 pulses. MEP measures will be obtained three times in order to establish a stable baseline. This procedure will be followed by TBS delivered to the optimal site in the motor cortex. TBS will be applied to the region of the primary motor cortex (M1) representing the hand. After TBS, MEPs will be acquired, at 0-, 10-, 20-, 30-, 40-, and 60-min post-stimulation.
Measured: Up to 2 week
Transient TBS-induced changes in language performance
Participants will be asked to perform a 40-item picture naming task pre/post TBS stimulation. Stimulation will occur at language cortex and vertex (order will be counterbalanced). Transient changes in naming abilities will be measured directly by assessing naming performance.
Measured: Up to 4 weeks
Secondary outcomes (1)
Safety and Tolerability of TBS in patient with aphasia
We will collect the number of patients with TMS-related adverse events.
Measured: Through study completion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Aug 2016 (estimated)
- Study startJul 2013
- Primary completionJun 2019
- Study completionJun 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for StrokeStudies of the same condition, open and under way.
- More trials run by University of PennsylvaniaThe 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 only
- Time perspective
- Cross-sectional
- Enrolment
- 41 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Pennsylvania
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Roy H Hamilton, MD, MS, Principal investigator, Neurology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02867670
- Sponsor's protocol ID
- 818784
- Status last verified
- Jul 2020
- First submitted
- 3 Jun 2016
- Last updated
- 8 Jul 2020
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Jul 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- TMS as a Biological Marker of Neuroplasticity
- ClinicalTrials.gov ID
- NCT02867670
- Acronym / sponsor ID
- 818784
- Keywords
- Transcranial Magnetic Stimulation (TMS)
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 41 participants (actual)
- Lead sponsor
- University of PennsylvaniaUniversity, hospital or other
- Study start
- Jul 2013
- Primary completion
- Jun 2019 (actual)
- Study completion
- Jun 2020 (actual)
- First posted
- 16 Aug 2016 (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.
TMS is a non-invasive brain stimulation technique, which can be used to change the activity of a person's brain cells without needles or surgery. In this study, the invesigators are interested in the brain's ability to adapt (also called "neuroplasticity") and regain language functioning after a stroke-specifically, they want to determine whether how a person's brain responds to TMS in the short term can be used to predict how well they will recover language abilities in the long term.
Detailed description
Aphasia is an impairment of language that may occur after a stroke (or other brain injuries). A person with aphasia may experience difficulties speaking, understanding speech, reading, writing, or any combination of these symptoms. Despite advances in understanding of language systems and functional neuroplasticity after brain injury, accurate predictors of aphasia recovery after stroke remain elusive. In order to better understand, predict, and enhance language improvement after stroke, there is a critical need to develop tools that can assess the influence of neuroplasticity on recovery.
Transcranial magnetic stimulation (TMS) is a non-invasive brain stimulation tool that has been used to predict the brain's neuroplastic capacity by assessing physiological responses observed immediately following administration of TMS. Additionally, difference in the physiological response to TMS have been shown to be affected by polymorphism in the gene coding for brain derived neurotrophic factor (BDNF). The current project explores the idea that because neural mechanisms of plasticity are essential determinants of both recovery after brain injury and physiologic response to TMS, magnetic brain stimulation could be employed as an indicator of the capacity for clinically relevant neuroplasticity, and potentially as a predictor of recovery from post-stroke deficits such as aphasia
The goals of this protocol are to 1) explore the utility of theta burst stimulation (TBS), a type of transcranial magnetic stimulation (TMS), as a tool for assessing neuroplasticity in the language system in patients with aphasia due to stroke, 2) and to assess the utility of TBS as a biomarker and predictor of functional recovery in patients with aphasia.
This protocol will encompass two separate but related experiments. In the first experiment, the investigators will apply TBS to brain regions that control language functions in aphasic patients in order to determine whether we can induce a transient improvement in naming ability. They will use a statistical model they have developed to categorize patients as either having High Plasticity or Low Plasticity. The investigators will determine whether this distinction predicts which patients are likely to have greater TBS-induced changes in language performance. In the second experiment, in the same patients, the investigators will apply TBS to the motor cortex to elicit changes in motor evoked potentials (MEPs). Using the same model to form matched groups, we predict that MEPs will be more attenuated in High Plasticity groups compared to the Low Plasticity group.
Study design
- Observational model
- Case only
- Time perspective
- Cross-sectional
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Transcranial Magnetic Stimulation of Motor Cortex | – | Device: Transcranial Magnetic StimulationAll study participants will receive real TMS stimulation over the primary motor cortex in order to collect physiological measures which will later be correlated with measures of neuroplasticity. There is NO placebo stimulation. |
| Transcranial Magnetic Stimulation of Language Cortex | – | Device: Transcranial Magnetic StimulationAll study participants will receive real TMS stimulation over the language cortex and a control site (i.e. vertex). Transient changes in speech production will be recorded and compared to measures of neuroplasticity. There is NO placebo stimulation. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Individuals who have had one or more strokes and are now experiencing the symptoms of aphasia. Aphasia is a communication disorder which may result in difficulties speaking,understanding speech, or both.
Key inclusion criteria (4 listed)
- Must have Aphasia due to stroke
- Stroke must have occurred at least 6 months ago
- Native English speaker
- Willing \& able to have a MRI
Key exclusion criteria (8 listed)
- Disorders of the brain other than stroke (i.e. tumor, Parkinsons, cancer... etc.)
- History of seizures/ or epilepsy
- Pacemaker or other implanted electronic devices
- Consumption of medications that lower seizure threshold
- History of psychiatric disorders
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 StimulationAlso: TMSTMS is a form of non-invasive brain stimulation which uses magnetic pulses to stimulate regions of the brain from outside the head, on the scalp. Specifically, TMS is performed with a copper-and-plastic coil that emits a magnetic field, which can affect brain cells in specific locations. In this study, researchers will also use a form of TMS called theta-burst stimulation (TBS), where TMS pulses are delivered rapidly over time. | Device | Transcranial Magnetic Stimulation of Language Cortex, Transcranial Magnetic Stimulation of Motor Cortex |
Primary outcome
Transient TBS-induced changes in motor evoked potentials (MEPs)
Time frame: Up to 2 week
Single-Pulse TMS will be used to measure MEPs prior to and after stimulation. When measuring MEPs, single pulses of TMS will be administered at approximately 120% of motor threshold, and with a minimum interstimulus interval of 5 seconds. Mean MEP amplitudes will be calculated by averaging the MEP amplitudes generated by 20 pulses. MEP measures will be obtained three times in order to establish a stable baseline. This procedure will be followed by TBS delivered to the optimal site in the motor cortex. TBS will be applied to the region of the primary motor cortex (M1) representing the hand. After TBS, MEPs will be acquired, at 0-, 10-, 20-, 30-, 40-, and 60-min post-stimulation.
Transient TBS-induced changes in language performance
Time frame: Up to 4 weeks
Participants will be asked to perform a 40-item picture naming task pre/post TBS stimulation. Stimulation will occur at language cortex and vertex (order will be counterbalanced). Transient changes in naming abilities will be measured directly by assessing naming performance.
1 secondary outcome
Safety and Tolerability of TBS in patient with aphasia
Time frame: Through study completion
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 8 Jul 2020.
- Lab WebsiteLink 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.
Roy H Hamilton, MD, MS principal investigator
Neurology
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 and Aphasia, run by University of Pennsylvania 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 4 inclusion and 8 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 8 Jul 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 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.
What does the primary outcome measure?
Transient TBS-induced changes in motor evoked potentials (MEPs) (time frame: Up to 2 week). The study lists 2 primary outcomes in all. 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 8 Jul 2020.