Normal PhysiologyNCT06050603
MRI Guided Closed-loop TMS-EEG
A study testing TMS in people with Normal Physiology and Amnestic Mild Cognitive Impairment, run by Sunnybrook Health Sciences Centre at 1 site in Canada.
Trial summary
The goal of this interventional study is to develop an individualized approach using transcranial magnetic stimulation (TMS) in a high-precision manner. This approach will use TMS to modulate brain activity at multiple locations simultaneously. Read more about this study
- Who is it for?
- Ages 18 to 80 yearsHealthy volunteers can take part
- Conditions the study is for
- Normal Physiology, Amnestic Mild Cognitive Impairment
- What is being tested?
- TMS
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 160 participants
- Where
- 1 siteCanada
- Study dates
- 7 Sep 2023to 31 Jul 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Ages between 18 and 65 years;
- Healthy with no history of neurological impairment;
- Normal or correct-to-normal vision.
- Age 50-80 years;
- MCI clinical criteria: (a) self- or informant-reported cognitive complaint; (b) preserved independence in functional abilities; and (c) absence of dementia;
- Objective cognitive impairment supported by the following measures of general cognitive function: (a) Mini-Mental State Exam (MMSE) 24-27 (inclusive); (b) Montreal Cognitive Assessment (MoCA) 18-26 (inclusive); or (c) Clinical Dementia Rating Scale score of 0.5;
- Normal or correct-to-normal vision.
Who cannot join
- Women who are pregnant or breastfeeding;
- History of seizure (childhood febrile seizures are acceptable and these subjects may be included in the study), history of epilepsy in self or first degree relatives, stroke, brain tumor, brain surgery, head injury, known structural brain lesion;
- Have metal in the eye or skull area, brain stimulator, surgical metal, clips in the brain, cochlear implants, mental fragments in the eye, as these make TMS unsafe;
- Have non-MRI compatible metal in the body, for example metallic (forromagnetic) implants (e.g., cardiac pacemaker, aneurysm clip);
- Subjects who are uncomfortable in small closed spaces (have claustrophobia), unable to lie comfortably supine for up to 1 hour, and would feel uncomfortable in the MRI machine;
- Participation in any other study involving non-invasive brain stimulation less than two weeks ago;
- Abnormal findings on neurological examination that we will perform.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Canada1 site, 1 recruiting
- Recruiting
Sunnybrook Health Sciences Centre
Toronto, Ontario, M4N 3M5
Fa-Hsuan Lin, PhD, 416-480-6100 ext. 65709, fhlin@sri.utoronto.ca
Hsin-Ju Lee, PhD, 416-480-6100 ext. 63285, hsinju.lee@utoronto.ca
About this study
Official title: Spatiotemporally Precise Neuromodulation by Transcranial Magnetic Stimulation Guided by Multimodal Neuroimaging
The goal of this interventional study is to develop an individualized approach using transcranial magnetic stimulation (TMS) in a high-precision manner. This approach will use TMS to modulate brain activity at multiple locations simultaneously. Functional magnetic resonance imaging (fMRI) and electroencephalograph (EEG) will record the responses and guide the stimulation. Specifically, the placement and orientation of TMS coils will be tailored to stimulate the targeted functional brain areas informed by fMRI. To maximize the interventional effect, stimulation pulses will be delivered based on EEG oscillations.
Read the detailed description
Background:
Transcranial magnetic stimulation (TMS) is a non-invasive technique that uses a transient electromagnetic field over a small area of the scalp to alter neuronal activity. It has been approved by Health Canada for the treatment of major depressive disorder and obsessive-compulsive disorder. Despite its clinical prevalence, TMS has a response rate of less than 50% and high intra- and inter-subject variability. Even among healthy subjects, the probability of inducing neuro-modulatory effects can be as low as 50%.
Design:
Depending on the study's aims, participants will have to visit Sunnybrook Health Sciences Centre two or three times on separate days. Participants will be screened with a medical record review before their first visit.
In the first visit, participants will have a magnetic resonance imaging (MRI) session. During the MRI session, participants will be brought inside an MRI scanner to collect images, including structural and functional MRI scans. During structural scans, participants will be asked to stay inside the MRI while images are taken. During functional MRI scans, participants will be asked to take rests with eyes open, watching and/or listening to audiovisual stimuli, and respond to stimuli by button pressing. Before starting MRI scans, a short training on the task will be taken. An additional assessment and, if necessary, training sessions will be conducted to ensure that participants undergo imaging while being able to keep their heads sufficiently for acceptable fMRI data quality. Before entering the MRI room, participants will be asked to remove any metal or magnetic sensitive objects (e.g., jewelry, keys, credit cards) to ensure safety. Earplugs or earphones will be provided to participants to reduce the loud noise produced by the MRI scanner. During the MRI scans, participants will perform the same task as notified in the training session. Short breaks will be arranged between tasks. The entire MRI procedure will take approximately one hour. If electroencephalograph (EEG) is to be recorded during MRI scans, an additional one hour is needed for EEG preparation before the MRI scans. After MRI scans, participants may be asked to rate their feelings toward the audiovisual stimuli, cognitive states, and emotional states on a computer.
Participants will be asked to attend TMS-MRI experiments twice on separate days for aim 1. In the TMS-MRI session, participants will take TMS and MRI separately. For TMS, participants will be led to a treatment room and seated in a comfortable chair in a slightly reclined position. A research staff will place an electromagnetic coil softly against each participant's head. A TMS coil will painlessly deliver magnetic pulses stimulating nerve cells at predetermined intervals. Electrodes may be mounted on the participants' wrists and around the eyes to monitor muscle activities. The treatment protocol for each participant will be based on his/her MRI scans, EEG signals, or motor responses. This step may be helped by using a camera. During TMS, participants will hear clicking sounds generated by the TMS coil and may have touching or twitching senses over their faces. After TMS, participants will be brought to an MRI room for MRI scans as described above. A rating of the participant's feelings and task performance may be taken after MRI scans.
For aims 2 and 3, participants will be asked to attend a TMS-EEG-MRI experiment once. In the TMS-EEG-MRI session, participants will first undergo TMS and EEG together. Then, participants will undergo an MRI. For TMS-EEG, participants will be led to a treatment room and seated in a comfortable chair in a slightly reclined position. Each participant will be asked to wear an EEG cap. A device is then used to measure the EEG electrode locations over the cap. Then, conductive gel will be applied to EEG electrodes over the cap. Participants may feel skin scratching when the research staffs apply the conductive gel. Additional electrodes will be attached around the participants' eyes and wrists to monitor muscle movement. During TMS, a research staff will place an electromagnetic coil softly against the participant's head. A TMS coil will painlessly deliver magnetic pulses that stimulate nerve cells. The investigators will determine the treatment protocol based on each participant's MRI scans, EEG signals, or motor responses. This step may be helped by using a camera. During TMS, participants will hear clicking sounds generated by the TMS coil and may have touching or twitching senses over their faces. After TMS, participants will be brought to an MRI room for MRI scans as described above. A rating of the participants' feelings and task performance may be taken after MRI scans.
- Being tested
- TMS
- Keywords
- Transcranial Magnetic Stimulation, Memory Impairments
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TMSDevice
The target locations of TMS will be cortical regions defined by either anatomical landmarks or functional regions derived from the individual's functional and structural MRI for Aim 1. TMS target locations for Aim 2 and 3 are determined by Aim 1's results. These TMS target regions will be guided by a navigation system.
TMS will be parametrically varied with combinations of pulse strength and frequencies based on experimental conditions. TMS strength will be referred to the resting motor threshold (rMT), which will be determined independently for each participant. TMS pulses will be delivered at fixed time instants for Aim 2 and at time instants based on the phase of oscillatory neural activity for Aim 3.
| Study group | Role | What they receive |
|---|---|---|
| Experimental_Aim1: Healthy Volunteers | Experimental | All participants will receive all conditions and the order of all conditions will be counterbalanced across participants. Statistical comparisons will be within-subjects. Receives: Device: TMS |
| Experimental_Aim2: Amnestic Mild Cognitive Impairment | Experimental | All participants will receive all conditions and the order of all conditions will be counterbalanced across participants. Statistical comparisons will be within-subjects. Receives: Device: TMS |
What is being measured
The primary outcome is the main question the study is designed to answer.
Functional connectivity measured by fMRI
Functional connectivity during resting state and psychological tasks
Measured: At baseline and immediately after treatment
Response accuracy to psychological tasks
accuracy, or rate of conditioned responses
Measured: At baseline and immediately after treatment
Reaction times
Measured: At baseline and immediately after treatment
Secondary outcomes (1)
EEG functional connectivity
Pearson correlation coefficients (r) between electrodes
Measured: At baseline and immediately after treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Sep 2023
- Study start7 Sep 2023
- Primary completion31 Jul 2027 (estimated)
- Study completion31 Jul 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Normal PhysiologyStudies of the same condition, open and under way.
- 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
- Single group
- Masking
- None (open label)
- Enrolment
- 160 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Sunnybrook Health Sciences Centre
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Fa-Hsuan Lin, Sunnybrook Health Sciences Centre
- Investigators
- Fa-Hsuan Lin, PhD, Principal investigator, Sunnybrook Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06050603
- Sponsor's protocol ID
- SUN-5474
- Status last verified
- Aug 2024
- First submitted
- 3 Sep 2023
- Last updated
- 13 Aug 2024
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Spatiotemporally Precise Neuromodulation by Transcranial Magnetic Stimulation Guided by Multimodal Neuroimaging
- ClinicalTrials.gov ID
- NCT06050603
- Acronym / sponsor ID
- SUN-5474
- Keywords
- Transcranial Magnetic Stimulation, Memory Impairments
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 160 participants (estimated)
- Lead sponsor
- Sunnybrook Health Sciences CentreUniversity, hospital or other
- Study start
- 7 Sep 2023 (actual)
- Primary completion
- 31 Jul 2027 (estimated)
- Study completion
- 31 Jul 2027 (estimated)
- First posted
- 22 Sep 2023 (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 goal of this interventional study is to develop an individualized approach using transcranial magnetic stimulation (TMS) in a high-precision manner. This approach will use TMS to modulate brain activity at multiple locations simultaneously. Functional magnetic resonance imaging (fMRI) and electroencephalograph (EEG) will record the responses and guide the stimulation. Specifically, the placement and orientation of TMS coils will be tailored to stimulate the targeted functional brain areas informed by fMRI. To maximize the interventional effect, stimulation pulses will be delivered based on EEG oscillations.
Detailed description
Background:
Transcranial magnetic stimulation (TMS) is a non-invasive technique that uses a transient electromagnetic field over a small area of the scalp to alter neuronal activity. It has been approved by Health Canada for the treatment of major depressive disorder and obsessive-compulsive disorder. Despite its clinical prevalence, TMS has a response rate of less than 50% and high intra- and inter-subject variability. Even among healthy subjects, the probability of inducing neuro-modulatory effects can be as low as 50%.
Design:
Depending on the study's aims, participants will have to visit Sunnybrook Health Sciences Centre two or three times on separate days. Participants will be screened with a medical record review before their first visit.
In the first visit, participants will have a magnetic resonance imaging (MRI) session. During the MRI session, participants will be brought inside an MRI scanner to collect images, including structural and functional MRI scans. During structural scans, participants will be asked to stay inside the MRI while images are taken. During functional MRI scans, participants will be asked to take rests with eyes open, watching and/or listening to audiovisual stimuli, and respond to stimuli by button pressing. Before starting MRI scans, a short training on the task will be taken. An additional assessment and, if necessary, training sessions will be conducted to ensure that participants undergo imaging while being able to keep their heads sufficiently for acceptable fMRI data quality. Before entering the MRI room, participants will be asked to remove any metal or magnetic sensitive objects (e.g., jewelry, keys, credit cards) to ensure safety. Earplugs or earphones will be provided to participants to reduce the loud noise produced by the MRI scanner. During the MRI scans, participants will perform the same task as notified in the training session. Short breaks will be arranged between tasks. The entire MRI procedure will take approximately one hour. If electroencephalograph (EEG) is to be recorded during MRI scans, an additional one hour is needed for EEG preparation before the MRI scans. After MRI scans, participants may be asked to rate their feelings toward the audiovisual stimuli, cognitive states, and emotional states on a computer.
Participants will be asked to attend TMS-MRI experiments twice on separate days for aim 1. In the TMS-MRI session, participants will take TMS and MRI separately. For TMS, participants will be led to a treatment room and seated in a comfortable chair in a slightly reclined position. A research staff will place an electromagnetic coil softly against each participant's head. A TMS coil will painlessly deliver magnetic pulses stimulating nerve cells at predetermined intervals. Electrodes may be mounted on the participants' wrists and around the eyes to monitor muscle activities. The treatment protocol for each participant will be based on his/her MRI scans, EEG signals, or motor responses. This step may be helped by using a camera. During TMS, participants will hear clicking sounds generated by the TMS coil and may have touching or twitching senses over their faces. After TMS, participants will be brought to an MRI room for MRI scans as described above. A rating of the participant's feelings and task performance may be taken after MRI scans.
For aims 2 and 3, participants will be asked to attend a TMS-EEG-MRI experiment once. In the TMS-EEG-MRI session, participants will first undergo TMS and EEG together. Then, participants will undergo an MRI. For TMS-EEG, participants will be led to a treatment room and seated in a comfortable chair in a slightly reclined position. Each participant will be asked to wear an EEG cap. A device is then used to measure the EEG electrode locations over the cap. Then, conductive gel will be applied to EEG electrodes over the cap. Participants may feel skin scratching when the research staffs apply the conductive gel. Additional electrodes will be attached around the participants' eyes and wrists to monitor muscle movement. During TMS, a research staff will place an electromagnetic coil softly against the participant's head. A TMS coil will painlessly deliver magnetic pulses that stimulate nerve cells. The investigators will determine the treatment protocol based on each participant's MRI scans, EEG signals, or motor responses. This step may be helped by using a camera. During TMS, participants will hear clicking sounds generated by the TMS coil and may have touching or twitching senses over their faces. After TMS, participants will be brought to an MRI room for MRI scans as described above. A rating of the participants' feelings and task performance may be taken after MRI scans.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Experimental_Aim1: Healthy Volunteers | Experimental | Device: TMSAll participants will receive all conditions and the order of all conditions will be counterbalanced across participants. Statistical comparisons will be within-subjects. |
| Experimental_Aim2: Amnestic Mild Cognitive Impairment | Experimental | Device: TMSAll participants will receive all conditions and the order of all conditions will be counterbalanced across participants. Statistical comparisons will be within-subjects. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Ages between 18 and 65 years;
- Healthy with no history of neurological impairment;
- Normal or correct-to-normal vision.
- Age 50-80 years;
- MCI clinical criteria: (a) self- or informant-reported cognitive complaint; (b) preserved independence in functional abilities; and (c) absence of dementia;
Key exclusion criteria (7 listed)
- Women who are pregnant or breastfeeding;
- History of seizure (childhood febrile seizures are acceptable and these subjects may be included in the study), history of epilepsy in self or first degree relatives, stroke, brain tumor, brain surgery, head injury, known structural brain lesion;
- Have metal in the eye or skull area, brain stimulator, surgical metal, clips in the brain, cochlear implants, mental fragments in the eye, as these make TMS unsafe;
- Have non-MRI compatible metal in the body, for example metallic (forromagnetic) implants (e.g., cardiac pacemaker, aneurysm clip);
- Subjects who are uncomfortable in small closed spaces (have claustrophobia), unable to lie comfortably supine for up to 1 hour, and would feel uncomfortable in the MRI machine;
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 |
|---|---|---|
| TMSThe target locations of TMS will be cortical regions defined by either anatomical landmarks or functional regions derived from the individual's functional and structural MRI for Aim 1. TMS target locations for Aim 2 and 3 are determined by Aim 1's results. These TMS target regions will be guided by a navigation system. TMS will be parametrically varied with combinations of pulse strength and frequencies based on experimental conditions. TMS strength will be referred to the resting motor threshold (rMT), which will be determined independently for each participant. TMS pulses will be delivered at fixed time instants for Aim 2 and at time instants based on the phase of oscillatory neural activity for Aim 3. | Device | Experimental_Aim1: Healthy Volunteers, Experimental_Aim2: Amnestic Mild Cognitive Impairment |
Primary outcome
Functional connectivity measured by fMRI
Time frame: At baseline and immediately after treatment
Functional connectivity during resting state and psychological tasks
Response accuracy to psychological tasks
Time frame: At baseline and immediately after treatment
accuracy, or rate of conditioned responses
Reaction times
Time frame: At baseline and immediately after treatment
1 secondary outcome
EEG functional connectivity
Time frame: At baseline and immediately after treatment
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Aug 2024.
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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.
Fa-Hsuan Lin, PhD principal investigator
Sunnybrook Research Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing TMS in people with Normal Physiology and Amnestic Mild Cognitive Impairment, run by Sunnybrook Health Sciences Centre at 1 site in Canada.
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 7 inclusion and 7 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: looking for participants now, as of the sponsor's last update on 13 Aug 2024. 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 Canada. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Fa-Hsuan Lin, PhD (416-480-6100 ext. 65709, fhlin@sri.utoronto.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Functional connectivity measured by fMRI (time frame: At baseline and immediately after treatment). The study lists 3 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 13 Aug 2024.