HealthyNCT03723434
Physiology of Interregional Connectivity in the Human Brain
A study testing Single-pulse transcranial magnetic stimulation (spTMS), Paired associative stimulation (PAS) and Repetitive transcranial magnetic stimulation (rTMS) in people with Healthy and Stroke, run by Shirley Ryan AbilityLab at 1 site in United States.
Trial summary
The purpose of this study is to understand the physiology of connectivity between cortical regions in the human brain in healthy participants and in patients with white matter lesions. Read more about this study
- Who is it for?
- Ages 18 to 85 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy, Stroke, Traumatic Brain Injury
- What is being tested?
- Single-pulse transcranial magnetic stimulation (spTMS), Paired associative stimulation (PAS) and Repetitive transcranial magnetic stimulation (rTMS)
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 76 participants
- Where
- 1 siteUnited States
- Study dates
- 31 May 2017to Nov 2020
- Phase
- Interventional
- 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 85 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Age from 18 to 85 years
- Right-handed
- Normal hearing and (corrected) vision
- Able to understand and give informed consent
- English speaker
- Age from 18 to 85 years
Show all 13Show fewer
- Stroke (ischemic subcortical, intermediate level, chronic phase 3 weeks or more from lesion)
- TBI (closed-skull, intermediate level, chronic phase 3 weeks or more from lesion)
- MS (white matter subcortical lesion)
- Clinical and radiological evidence supporting the above diagnoses
- One or more behavioral symptoms possibly linked to the white matter lesion(s)
- Stable medical condition
- English speaker
Who cannot join
- Cardiac pacemaker or pacemaker wires; neurostimulators; implanted pumps
- Metal in the body (rods, plates, screws, shrapnel, dentures, IUD) or metallic particles in the eye
- Surgical clips in the head or previous neurosurgery
- Any magnetic particles in the body
- Cochlear implants
- Prosthetic heart valves
Show all 19Show fewer
- Epilepsy or any other type of seizure history
- Any neurological diagnoses or medications influencing brain function
- History of significant head trauma (i.e., extended loss of consciousness, neurological sequelae)
- Known structural brain lesion
- Significant other disease (heart disease, malignant tumors, mental disorders)
- Significant claustrophobia; Ménière's disease
- Pregnancy (ruled out by urine ß-HCG if answers to screening questions suggest that pregnancy is possible), breast feeding
- Non prescribed drug use
- Failure to perform the behavioral tasks or neuropsychological evaluation tests
- Prisoners
- Same as above, excluding the requirement of no structural brain lesion, and medications influencing brain function are allowed
- Patients with cortical lesions or CSF-filled cysts/cavities near the TMS sites
- MS patients with acute exacerbation
Trial locations and contacts
1 site in 1 country.
United States1 site, 1 recruiting
- Recruiting
Shirley Ryan AbilityLab
Chicago, Illinois, 60611
Tommi Raij, MD, PhD, 312-238-4401, tommi.raij@northwestern.edu
About this study
The purpose of this study is to understand the physiology of connectivity between cortical regions in the human brain in healthy participants and in patients with white matter lesions. Specifically, the investigators will examine the effects of paired associative stimulation (PAS) which consists in delivering brief (< 1 ms) current pulses separated by a short millisecond-level time interval ("asynchrony") to two cortical areas. The used techniques are all non-invasive and considered safe in humans: transcranial magnetic stimulation (TMS), electroencephalography (EEG), magnetic resonance imaging (MRI), and functional MRI (fMRI). Based on prior literature in animals and human studies, it is hypothesized that PAS may increase or decrease effective connectivity between the stimulated areas depending on the asynchrony value. The main outcome measure is source-resolved EEG responses evoked by single-pulse TMS; this is a more direct measure of neuronal changes occurring at the targeted cortical area than motor evoked potentials (MEPs) or sensor-level EEG responses used in previous studies.
Read the detailed description
This study consists of two experiments.
In Experiment A, healthy participants without disorders or medications influencing brain function (N=24) will be recruited. A range of negative and positive asynchronies (from minus 50 to + 50 ms) will be tested. To allow comparison with prior studies that used MEPs as outcome measures, in 12 participants the primary motor cortex in the left and right hemisphere will be targeted. In another 12 participants, two cortical areas within the same hemisphere will be stimulated.
In Experiment B, participants with stroke, traumatic brain injury (TBI), or multiple sclerosis (MS) (total maximum N across all such participants is 52) will be recruited. These participants are required to have one or more subcortical white matter lesions, which would be expected to result in cortico-cortical disconnections. Here, the investigators will only test PAS with positive asynchronies, with the goal of testing if the findings observed in healthy participants are similar in participants with white matter lesions. It will also be examined if the PAS-induced connectivity changes persist beyond the stimulation sessions if PAS is given repeatedly over several days. PAS will be applied to two cortical targets that have been disconnected from each other. The rationale for including more than one disorder in Experiment B is that the disconnections are in all cases caused by white matter lesions and the results may therefore be similar. To detect possible differences between disorders, the data from the three groups will also be analyzed separately.
- Conditions
- Healthy, Stroke, Traumatic Brain Injury, Multiple Sclerosis
- Being tested
- Single-pulse transcranial magnetic stimulation (spTMS), Paired associative stimulation (PAS), Repetitive transcranial magnetic stimulation (rTMS)
- Keywords
- Human, Brain, Connectivity, Stroke, Traumatic brain injury, Multiple sclerosis, Transcranial magnetic stimulation, Paired associative stimulation, Electroencephalography, Magnetic resonance imaging
- Medical subject headings
- Stroke, Brain Injuries, Traumatic, Multiple Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Single-pulse transcranial magnetic stimulation (spTMS)Device
Single-pulse TMS (spTMS) will be delivered with a TMS stimulator (MagPro X100 w/ MagOption, MagVenture, Farum, Denmark) and a figure-of-eight TMS coil. 80 spTMS will be repeated at 0.2 Hz. An MRI-based TMS navigation system will be used to navigate the TMS coil (Localite, St Augustin, Germany).
Paired associative stimulation (PAS)Device
Paired associative stimulation (PAS) will be applied with two TMS stimulators (MagPro X100 w/ MagOption, MagVenture, Farum, Denmark) and two TMS coils. The pulses from each stimulator/coil will be repeated at 0.2 Hz, duration of run 15 minutes (180 pulses for each stimulator/coil). In different sessions, we will deliver PAS with different asynchrony values to examine their effects on effective connectivity. Coils will be navigated using an MRI-based TMS navigation system (Localite, St Augustin, Germany).
Repetitive transcranial magnetic stimulation (rTMS)Device
Repetitive TMS (rTMS) will be applied at 1 and 20 Hz with a TMS stimulator (MagPro X100 w/ MagOption, MagVenture, Farum, Denmark) and a figure-of-eight TMS coil. 300 rTMS pulses will be delivered during 1 and 20 Hz stimulation. An MRI-based TMS navigation system will be used to navigate the TMS coil (Localite, St Augustin, Germany).
| Study group | Role | What they receive |
|---|---|---|
| Healthy Participants | Active comparator | Healthy participants without disorders or medications influencing brain function will be scanned with MRI and undergo single-pulse TMS and PAS during several visits, each with a different asynchrony, while EEG and MEPs are recorded. Receives: Device: Single-pulse transcranial magnetic stimulation (spTMS); Device: Paired associative stimulation (PAS); Device: Repetitive transcranial magnetic stimulation (rTMS) |
| Patients | Experimental | Participants with stroke, traumatic brain injury (TBI), or multiple sclerosis (MS) will be scanned with MRI and undergo single-pulse TMS and paired associative stimulation during several visits while EEG is recorded. Receives: Device: Single-pulse transcranial magnetic stimulation (spTMS); Device: Paired associative stimulation (PAS) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes in EEG effective connectivity
EEG will be recorded with a 64-channel whole-head TMS-compatible device (NeurOne, Bittium, Kuopio, Finland). Data will be collected before (Pre-PAS) and at 1 minute (Post-PAS T1) and at 60 minutes (Post-PAS T60) after PAS. To record spTMS-evoked EEG responses the investigators will deliver 80 single TMS pulses to the two areas receiving PAS, one target after the other in separate runs. Effective connectivity will be measured by comparing the source-resolved EEG evoked response waveforms before (Pre-PAS) and at 1 (Post-PAS T1) and at 60 minutes after PAS (Post-PAS T60).
Measured: Experiment A: Within-session (before versus after PAS at 1 and 60 minutes). Experiment B: Within-session (before versus after PAS at 1 and 60 minutes). Across-sessions (persistence of changes up to 1 month after last PAS session).
Changes in resting-state EEG coherence
Resting-state EEG will be recorded with a 64-channel whole-head device (NeurOne, Bittium, Kuopio, Finland). Data will be collected before (Pre-PAS) and at 1 minute (Post-PAS T1) and at 60 minutes (Post-PAS T60) after PAS. Resting-state EEG coherence will be computed in the source space for the two areas receiving PAS from 1 to 100 Hz.
Measured: Experiment A: Within-session (before versus after PAS at 1 and 60 minutes). Experiment B: Within-session (before versus after PAS at 1 and 60 minutes). Across-sessions (persistence of changes up to 1 month after last PAS session).
Secondary outcomes (3)
Motor evoked potentials (MEPs)
To assess the effects of PAS in participants where the primary motor cortex (M1) was targeted, spTMS will be administered to the M1 at 110% of resting motor threshold (rMT) while MEPs are recorded from the contralateral hand (NeurOne, Bittium, Kuopio, Finland). The MEPs will be recorded before (Pre-PAS), at 1 minute (Post-PAS T1) and at 60 minutes (Post-PAS T60) after PAS.
Measured: Experiment A: Within-session (before versus after PAS at 1 and 60 minutes). Experiment B: Done only in patients where the M1 was targeted with PAS.
MRI functional connectivity
Functional connectivity will be assessed with resting-state MRI (rs-MRI).
Measured: Experiment A: Baseline. Experiment B: Baseline to 1 month after the last PAS session.
MRI structural connectivity
Structural connectivity will be assessed with diffusion tensor imaging (DTI).
Measured: Experiment A: Baseline. Experiment B: Baseline to 1 month after the last PAS session.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Oct 2018
- Study start31 May 2017
- Primary completionNov 2020 (estimated)
- Study completionNov 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HealthyStudies of the same condition, open and under way.
- More trials run by Shirley Ryan AbilityLabThe 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
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- PAS will be applied to two cortical targets at different asynchronies to modulate connectivity. PAS may selectively increase or decrease effective connectivity depending on the asynchrony. Negative asynchronies are expected to decrease effective connectivity, whereas positive asynchronies to increase it.
- Masking
- None (open label)
- Enrolment
- 76 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Shirley Ryan AbilityLab
- Sponsor type
- University, hospital or other
- Collaborators
- Northwestern University
- Responsible party
- Principal investigator, Tommi Raij, Shirley Ryan AbilityLab
- Investigators
- Tommi Raij, MD, PhD, Principal investigator, Shirley Ryan AbilityLab 355 East Erie St, Chicago, IL Department of Physical Medicine and Rehabilitation, Feinberg School of Medicine, Northwestern University, Chicago, IL
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03723434
- Sponsor's protocol ID
- STU00204239
- Status last verified
- Oct 2018
- First submitted
- 22 Oct 2018
- Last updated
- 29 Oct 2018
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Oct 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Physiology of Interregional Connectivity in the Human Brain
- ClinicalTrials.gov ID
- NCT03723434
- Acronym / sponsor ID
- STU00204239
- Conditions
- Healthy, Stroke, Traumatic Brain Injury, Multiple Sclerosis
- Keywords
- Human, Brain, Connectivity, Stroke, Traumatic brain injury, Multiple sclerosis, Transcranial magnetic stimulation, Paired associative stimulation
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 76 participants (estimated)
- Lead sponsor
- Shirley Ryan AbilityLabUniversity, hospital or other
- Collaborators
- Northwestern University
- Study start
- 31 May 2017 (actual)
- Primary completion
- Nov 2020 (estimated)
- Study completion
- Nov 2020 (estimated)
- First posted
- 29 Oct 2018 (actual)
- 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.
The purpose of this study is to understand the physiology of connectivity between cortical regions in the human brain in healthy participants and in patients with white matter lesions. Specifically, the investigators will examine the effects of paired associative stimulation (PAS) which consists in delivering brief (< 1 ms) current pulses separated by a short millisecond-level time interval ("asynchrony") to two cortical areas. The used techniques are all non-invasive and considered safe in humans: transcranial magnetic stimulation (TMS), electroencephalography (EEG), magnetic resonance imaging (MRI), and functional MRI (fMRI). Based on prior literature in animals and human studies, it is hypothesized that PAS may increase or decrease effective connectivity between the stimulated areas depending on the asynchrony value. The main outcome measure is source-resolved EEG responses evoked by single-pulse TMS; this is a more direct measure of neuronal changes occurring at the targeted cortical area than motor evoked potentials (MEPs) or sensor-level EEG responses used in previous studies.
Detailed description
This study consists of two experiments.
In Experiment A, healthy participants without disorders or medications influencing brain function (N=24) will be recruited. A range of negative and positive asynchronies (from minus 50 to + 50 ms) will be tested. To allow comparison with prior studies that used MEPs as outcome measures, in 12 participants the primary motor cortex in the left and right hemisphere will be targeted. In another 12 participants, two cortical areas within the same hemisphere will be stimulated.
In Experiment B, participants with stroke, traumatic brain injury (TBI), or multiple sclerosis (MS) (total maximum N across all such participants is 52) will be recruited. These participants are required to have one or more subcortical white matter lesions, which would be expected to result in cortico-cortical disconnections. Here, the investigators will only test PAS with positive asynchronies, with the goal of testing if the findings observed in healthy participants are similar in participants with white matter lesions. It will also be examined if the PAS-induced connectivity changes persist beyond the stimulation sessions if PAS is given repeatedly over several days. PAS will be applied to two cortical targets that have been disconnected from each other. The rationale for including more than one disorder in Experiment B is that the disconnections are in all cases caused by white matter lesions and the results may therefore be similar. To detect possible differences between disorders, the data from the three groups will also be analyzed separately.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- PAS will be applied to two cortical targets at different asynchronies to modulate connectivity. PAS may selectively increase or decrease effective connectivity depending on the asynchrony. Negative asynchronies are expected to decrease effective connectivity, whereas positive asynchronies to increase it.
| Arm | Type | Receives |
|---|---|---|
| Healthy Participants | Active comparator | Device: Single-pulse transcranial magnetic stimulation (spTMS), Device: Paired associative stimulation (PAS), Device: Repetitive transcranial magnetic stimulation (rTMS)Healthy participants without disorders or medications influencing brain function will be scanned with MRI and undergo single-pulse TMS and PAS during several visits, each with a different asynchrony, while EEG and MEPs are recorded. |
| Patients | Experimental | Device: Single-pulse transcranial magnetic stimulation (spTMS), Device: Paired associative stimulation (PAS)Participants with stroke, traumatic brain injury (TBI), or multiple sclerosis (MS) will be scanned with MRI and undergo single-pulse TMS and paired associative stimulation during several visits while EEG is recorded. |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Age from 18 to 85 years
- Right-handed
- Normal hearing and (corrected) vision
- Able to understand and give informed consent
- English speaker
Key exclusion criteria (19 listed)
- Cardiac pacemaker or pacemaker wires; neurostimulators; implanted pumps
- Metal in the body (rods, plates, screws, shrapnel, dentures, IUD) or metallic particles in the eye
- Surgical clips in the head or previous neurosurgery
- Any magnetic particles in the body
- Cochlear implants
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 |
|---|---|---|
| Single-pulse transcranial magnetic stimulation (spTMS)Single-pulse TMS (spTMS) will be delivered with a TMS stimulator (MagPro X100 w/ MagOption, MagVenture, Farum, Denmark) and a figure-of-eight TMS coil. 80 spTMS will be repeated at 0.2 Hz. An MRI-based TMS navigation system will be used to navigate the TMS coil (Localite, St Augustin, Germany). | Device | Healthy Participants, Patients |
| Paired associative stimulation (PAS)Paired associative stimulation (PAS) will be applied with two TMS stimulators (MagPro X100 w/ MagOption, MagVenture, Farum, Denmark) and two TMS coils. The pulses from each stimulator/coil will be repeated at 0.2 Hz, duration of run 15 minutes (180 pulses for each stimulator/coil). In different sessions, we will deliver PAS with different asynchrony values to examine their effects on effective connectivity. Coils will be navigated using an MRI-based TMS navigation system (Localite, St Augustin, Germany). | Device | Healthy Participants, Patients |
| Repetitive transcranial magnetic stimulation (rTMS)Repetitive TMS (rTMS) will be applied at 1 and 20 Hz with a TMS stimulator (MagPro X100 w/ MagOption, MagVenture, Farum, Denmark) and a figure-of-eight TMS coil. 300 rTMS pulses will be delivered during 1 and 20 Hz stimulation. An MRI-based TMS navigation system will be used to navigate the TMS coil (Localite, St Augustin, Germany). | Device | Healthy Participants |
Primary outcome
Changes in EEG effective connectivity
Time frame: Experiment A: Within-session (before versus after PAS at 1 and 60 minutes). Experiment B: Within-session (before versus after PAS at 1 and 60 minutes). Across-sessions (persistence of changes up to 1 month after last PAS session).
EEG will be recorded with a 64-channel whole-head TMS-compatible device (NeurOne, Bittium, Kuopio, Finland). Data will be collected before (Pre-PAS) and at 1 minute (Post-PAS T1) and at 60 minutes (Post-PAS T60) after PAS. To record spTMS-evoked EEG responses the investigators will deliver 80 single TMS pulses to the two areas receiving PAS, one target after the other in separate runs. Effective connectivity will be measured by comparing the source-resolved EEG evoked response waveforms before (Pre-PAS) and at 1 (Post-PAS T1) and at 60 minutes after PAS (Post-PAS T60).
Changes in resting-state EEG coherence
Time frame: Experiment A: Within-session (before versus after PAS at 1 and 60 minutes). Experiment B: Within-session (before versus after PAS at 1 and 60 minutes). Across-sessions (persistence of changes up to 1 month after last PAS session).
Resting-state EEG will be recorded with a 64-channel whole-head device (NeurOne, Bittium, Kuopio, Finland). Data will be collected before (Pre-PAS) and at 1 minute (Post-PAS T1) and at 60 minutes (Post-PAS T60) after PAS. Resting-state EEG coherence will be computed in the source space for the two areas receiving PAS from 1 to 100 Hz.
3 secondary outcomes
Motor evoked potentials (MEPs)
Time frame: Experiment A: Within-session (before versus after PAS at 1 and 60 minutes). Experiment B: Done only in patients where the M1 was targeted with PAS.
MRI functional connectivity
Time frame: Experiment A: Baseline. Experiment B: Baseline to 1 month after the last PAS session.
MRI structural connectivity
Time frame: Experiment A: Baseline. Experiment B: Baseline to 1 month after the last PAS session.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Oct 2018.
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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.
Tommi Raij, MD, PhD principal investigator
Shirley Ryan AbilityLab 355 East Erie St, Chicago, IL Department of Physical Medicine and Rehabilitation, Feinberg School of Medicine, Northwestern University, Chicago, IL
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Single-pulse transcranial magnetic stimulation (spTMS), Paired associative stimulation (PAS) and Repetitive transcranial magnetic stimulation (rTMS) in people with Healthy and Stroke, run by Shirley Ryan AbilityLab 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 13 inclusion and 19 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: status not confirmed, as of the sponsor's last update on 29 Oct 2018. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Tommi Raij, MD, PhD (312-238-4401, tommi.raij@northwestern.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Changes in EEG effective connectivity (time frame: Experiment A: Within-session (before versus after PAS at 1 and 60 minutes). Experiment B: Within-session (before versus after PAS at 1 and 60 minutes). Across-sessions (persistence of changes up to 1 month after last PAS session).). 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 29 Oct 2018.