Mesial Temporal Lobe EpilepsyNCT06521437
Hippocampal Network Function in Epilepsy
A study testing TMS targeting the hippocampus indirectly via its network in people with Mesial Temporal Lobe Epilepsy, run by University of Chicago at 1 site in United States.
Trial summary
The aim of this pilot study is to understand hippocampal network function in mesial temporal lobe epilepsy (MTLE) and to test whether transcranial magnetic stimulation (TMS) targeting the network of the hippocampus can change hippocampal-dependent memory task performance and epileptic activity in people with (MTLE). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Mesial Temporal Lobe Epilepsy
- What is being tested?
- TMS targeting the hippocampus indirectly via its network
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 34 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Jul 2024to Dec 2028
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diagnosis of (pharmacoresistant) MTLE
- Age 18+ years old
- Native English speakers
- Normal or corrected-to-normal near and far vision
- Stable antiepileptic drugs (AED) regimen (unchanged for at least 1 month)
Who cannot join
- Diagnosis of neurological illness other than MTLE
- Taking drugs that impair cognition other than anticonvulsive medication for the treatment of MTLE (e.g., antipsychotics or psychostimulants).
- Children under the age of 18 years
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
About this study
The aim of this pilot study is to understand hippocampal network function in mesial temporal lobe epilepsy (MTLE) and to test whether transcranial magnetic stimulation (TMS) targeting the network of the hippocampus can change hippocampal-dependent memory task performance and epileptic activity in people with (MTLE). Positive findings would implicate the hippocampal network as a source of these typical primary MTLE symptoms.
Subjects with a primary diagnosis of MTLE will be enrolled in a non-randomized, non-blinded pilot experiment to test target engagement and preliminary efficacy of a novel neurostimulation approach targeting the hippocampal network. At baseline, subjects will undergo neurocognitive testing for hippocampal-dependent memory and functional magnetic resonance imagining (fMRI) neuroimaging assessment of brain structure and task-dependent activity. They will also receive scalp-electroencephalography (EEG) to measure interictal epileptiform discharge (IED) frequency at baseline, and will complete a seizure diary for one month. They will then receive high-frequency repetitive TMS targeting an area of parieto-occipital cortex defined based on fMRI connectivity with the hippocampus measured at baseline. The baseline assessments will then be repeated, using an alternate form of the memory test. The investigators will analyze changes from baseline in memory task performance, fMRI activity of the hippocampal network, IED frequency, and reported seizure frequency.
Read the detailed description
The purpose of this pilot study is to investigate hippocampal network dysfunction associated with mesial temporal lobe epilepsy (MTLE) and to examine whether network-targeted transcranial magnetic stimulation (TMS) can affect hippocampal connectivity, cognitive performance, and epileptic activity observed in adult subjects with MTLE.
Subjects will be recruited through the University of Chicago Medicine Comprehensive Epilepsy Center and other local epilepsy centers. Subjects will complete up to 8 experimental sessions (1 baseline experiment/assessment, up to 5 TMS sessions, up to 2 post-treatment experiments/assessments), spread over a two-month period. During the baseline and post-treatment sessions, subjects will undergo electroencephalography (EEG) and functional magnetic resonance imaging (fMRI). EEG will be utilized to examine interictal epileptiform discharge (IED) frequency at rest as well as task-related neural activity recorded from non-invasive scalp EEG electrodes at locations conforming to the International 10-20 positioning system with additional anterior temporal electrodes. MRI scanning procedures will take approximately 45 minutes and include native anatomical (MP-RAGE) as well as functional (EPI) sequences to assess hippocampal network function and task-related activity. During both, the EEG and MRI procedures, subjects will perform a memory task.
One month following the baseline session, subjects will return to the lab for up to 5 TMS intervention sessions. During the one-month period preceding TMS, subjects will complete a daily seizure diary to track baseline seizure frequency prior to the intervention. TMS parameters are determined based on the allowable dosage of TMS delivery, calculated based on published standards for experimental TMS protocols, and in accordance with standard operating procedures for TMS. Subjects will receive brief (~2 to 40s) trains of repetitive TMS with long (>10s) inter-train intervals. Each train of repetitive TMS will include between 20 and 40 individual pulses delivered at frequencies hypothesized to have different effects on memory (e.g., in the theta range). Individual pulse intensity will be calibrated using the motor-threshold method. Post-treatment sessions will once again comprise EEG and fMRI procedures as described above. Following the post-treatment sessions, subjects will continue to complete a daily seizure diary for the next 30 days to track any changes to seizures following treatment. Pre- and post-stimulation data will be compared to assess effects of the intervention on memory performance, hippocampal network function, and epileptic activity.
- Conditions
- Mesial Temporal Lobe Epilepsy
- Being tested
- TMS targeting the hippocampus indirectly via its network
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TMS targeting the hippocampus indirectly via its networkDevice
Subjects will receive high-frequency repetitive TMS to a parieto-occipital location defined in each subject based on high resting-state fMRI connectivity with the hippocampus at baseline
| Study group | Role | What they receive |
|---|---|---|
| Experiment 1 | Experimental | Subjects will be tested for baseline performance on a memory task while in an MRI scanner and with scalp EEG. Subjects will then receive multiple sessions, of repetitive transcranial magnetic stimulation. Post-treatment, baseline assessments will be repeated. Overall study period per subject: 2 months Receives: Device: TMS targeting the hippocampus indirectly via its network |
What is being measured
The primary outcome is the main question the study is designed to answer.
Epileptic activity (IEDs)
Scalp EEG is used to measure IEDs, identified via clinical assessment and quantified
Measured: Measured at baseline and 1 day after stimulation
Secondary outcomes (3)
Memory task performance
Subjects memorize word pairs and then attempt to recall the missing word given one item from each pair after a delay. Total number of words pairs recalled will be measured.
Measured: The memory task is administered at baseline and 1 day after the last stimulation session. Recall will be measured approximately 15 minutes after seeing the word pairs.
fMRI connectivity of the hippocampal network
Subjects will undergo MRI neuroimaging assessment of brain structure and resting-state function. The correlation between the hippocampus and parietal cortex will be measured.
Measured: First day of study (baseline session) and 1 day after last stimulation session.
Seizure frequency reported in seizure diary
Subjects will complete an online seizure diary daily. Number of daily seizures reported will be measured.
Measured: From the baseline session to 30 days following the post-treatment sessions
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jul 2024
- Study start1 Jul 2024
- Primary completionDec 2028 (estimated)
- Study completionDec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Mesial Temporal Lobe EpilepsyStudies of the same condition, open and under way.
- More trials run by University of ChicagoThe 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 34 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Chicago
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Joel Voss, PhD, Principal investigator, University of Chicago
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06521437
- Sponsor's protocol ID
- IRB23-1089
- Status last verified
- Sep 2025
- First submitted
- 8 Jul 2024
- Last updated
- 12 Sep 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Publications
Rossi S, Hallett M, Rossini PM, Pascual-Leone A; Safety of TMS Consensus Group. Safety, ethical considerations, and application guidelines for the use of transcranial magnetic stimulation in clinical practice and research. Clin Neurophysiol. 2009 Dec;120(12):2008-2039. doi: 10.1016/j.clinph.2009.08.016. Epub 2009 Oct 14.
PubMed 19833552
Study at a glance
From the registry record, last updated by the sponsor on 12 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Hippocampal Network Function in Epilepsy
- ClinicalTrials.gov ID
- NCT06521437
- Acronym / sponsor ID
- IRB23-1089
- Conditions
- Mesial Temporal Lobe Epilepsy
- Study type
- Interventional
- Recruitment status
- Enrolling by invitation
- Enrolment
- 34 participants (estimated)
- Lead sponsor
- University of ChicagoUniversity, hospital or other
- Study start
- 1 Jul 2024 (actual)
- Primary completion
- Dec 2028 (estimated)
- Study completion
- Dec 2028 (estimated)
- First posted
- 26 Jul 2024 (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 aim of this pilot study is to understand hippocampal network function in mesial temporal lobe epilepsy (MTLE) and to test whether transcranial magnetic stimulation (TMS) targeting the network of the hippocampus can change hippocampal-dependent memory task performance and epileptic activity in people with (MTLE). Positive findings would implicate the hippocampal network as a source of these typical primary MTLE symptoms.
Subjects with a primary diagnosis of MTLE will be enrolled in a non-randomized, non-blinded pilot experiment to test target engagement and preliminary efficacy of a novel neurostimulation approach targeting the hippocampal network. At baseline, subjects will undergo neurocognitive testing for hippocampal-dependent memory and functional magnetic resonance imagining (fMRI) neuroimaging assessment of brain structure and task-dependent activity. They will also receive scalp-electroencephalography (EEG) to measure interictal epileptiform discharge (IED) frequency at baseline, and will complete a seizure diary for one month. They will then receive high-frequency repetitive TMS targeting an area of parieto-occipital cortex defined based on fMRI connectivity with the hippocampus measured at baseline. The baseline assessments will then be repeated, using an alternate form of the memory test. The investigators will analyze changes from baseline in memory task performance, fMRI activity of the hippocampal network, IED frequency, and reported seizure frequency.
Detailed description
The purpose of this pilot study is to investigate hippocampal network dysfunction associated with mesial temporal lobe epilepsy (MTLE) and to examine whether network-targeted transcranial magnetic stimulation (TMS) can affect hippocampal connectivity, cognitive performance, and epileptic activity observed in adult subjects with MTLE.
Subjects will be recruited through the University of Chicago Medicine Comprehensive Epilepsy Center and other local epilepsy centers. Subjects will complete up to 8 experimental sessions (1 baseline experiment/assessment, up to 5 TMS sessions, up to 2 post-treatment experiments/assessments), spread over a two-month period. During the baseline and post-treatment sessions, subjects will undergo electroencephalography (EEG) and functional magnetic resonance imaging (fMRI). EEG will be utilized to examine interictal epileptiform discharge (IED) frequency at rest as well as task-related neural activity recorded from non-invasive scalp EEG electrodes at locations conforming to the International 10-20 positioning system with additional anterior temporal electrodes. MRI scanning procedures will take approximately 45 minutes and include native anatomical (MP-RAGE) as well as functional (EPI) sequences to assess hippocampal network function and task-related activity. During both, the EEG and MRI procedures, subjects will perform a memory task.
One month following the baseline session, subjects will return to the lab for up to 5 TMS intervention sessions. During the one-month period preceding TMS, subjects will complete a daily seizure diary to track baseline seizure frequency prior to the intervention. TMS parameters are determined based on the allowable dosage of TMS delivery, calculated based on published standards for experimental TMS protocols, and in accordance with standard operating procedures for TMS. Subjects will receive brief (~2 to 40s) trains of repetitive TMS with long (>10s) inter-train intervals. Each train of repetitive TMS will include between 20 and 40 individual pulses delivered at frequencies hypothesized to have different effects on memory (e.g., in the theta range). Individual pulse intensity will be calibrated using the motor-threshold method. Post-treatment sessions will once again comprise EEG and fMRI procedures as described above. Following the post-treatment sessions, subjects will continue to complete a daily seizure diary for the next 30 days to track any changes to seizures following treatment. Pre- and post-stimulation data will be compared to assess effects of the intervention on memory performance, hippocampal network function, and epileptic activity.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Experiment 1 | Experimental | Device: TMS targeting the hippocampus indirectly via its networkSubjects will be tested for baseline performance on a memory task while in an MRI scanner and with scalp EEG. Subjects will then receive multiple sessions, of repetitive transcranial magnetic stimulation. Post-treatment, baseline assessments will be repeated. Overall study period per subject: 2 months |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Diagnosis of (pharmacoresistant) MTLE
- Age 18+ years old
- Native English speakers
- Normal or corrected-to-normal near and far vision
- Stable antiepileptic drugs (AED) regimen (unchanged for at least 1 month)
Key exclusion criteria (3 listed)
- Diagnosis of neurological illness other than MTLE
- Taking drugs that impair cognition other than anticonvulsive medication for the treatment of MTLE (e.g., antipsychotics or psychostimulants).
- Children under the age of 18 years
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 |
|---|---|---|
| TMS targeting the hippocampus indirectly via its networkSubjects will receive high-frequency repetitive TMS to a parieto-occipital location defined in each subject based on high resting-state fMRI connectivity with the hippocampus at baseline | Device | Experiment 1 |
Primary outcome
Epileptic activity (IEDs)
Time frame: Measured at baseline and 1 day after stimulation
Scalp EEG is used to measure IEDs, identified via clinical assessment and quantified
3 secondary outcomes
Memory task performance
Time frame: The memory task is administered at baseline and 1 day after the last stimulation session. Recall will be measured approximately 15 minutes after seeing the word pairs.
fMRI connectivity of the hippocampal network
Time frame: First day of study (baseline session) and 1 day after last stimulation session.
Seizure frequency reported in seizure diary
Time frame: From the baseline session to 30 days following the post-treatment sessions
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 12 Sep 2025.
- Background: PubMed 19833552Rossi S, Hallett M, Rossini PM, Pascual-Leone A; Safety of TMS Consensus Group. Safety, ethical considerations, and application guidelines for the use of transcranial magnetic stimulation in clinical practice and research. Clin Neurophysiol. 2009 Dec;120(12):2008-2039. doi: 10.1016/j.clinph.2009.08.016. Epub 2009 Oct 14.
- Individual participant dataSharing planned: No
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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.
Joel Voss, PhD principal investigator
University of Chicago
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 targeting the hippocampus indirectly via its network in people with Mesial Temporal Lobe Epilepsy, run by University of Chicago 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 5 inclusion and 3 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: enrolling by invitation, as of the sponsor's last update on 12 Sep 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?
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?
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?
Epileptic activity (IEDs) (time frame: Measured at baseline and 1 day after stimulation). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06521437, which also lists 1 linked publication.
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 12 Sep 2025; AzTrials last refreshed its copy on 28 Oct 2026.