Functional Neurological Symptom DisorderEarly Phase 1FND-seizNCT07059325

Accelerated TMS for Seizure-Type Functional Neurologic Disorders

A Early Phase 1 study testing Transcranial Magnetic Stimulation in people with Functional Neurological Symptom Disorder and Functional Seizures, run by Medical University of South Carolina at 1 site in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts

Official record

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Trial summary

Who is it for?: Ages 18 to 65 years
Conditions the study is for: Functional Neurological Symptom Disorder, Functional Seizures
What is being tested?: Transcranial Magnetic Stimulation
Type of treatment: Medical device
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 30 participants
Where: 1 siteUnited States
Study dates: 2 Sep 2025to 1 Jul 2027
Phase: Early Phase 1
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 65 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

>18 years old and <65 years old
English Speaking, can read and write, and able to provide informed consent
Diagnosis of "documented" Functional Seizures as made by an MUSC epileptologist or neurologist using the ILAE recommendations: "by clinician experienced in diagnosis of seizure disorders (on video or in person), showing semiology of typical of FND-seiz, while on EEG plus no epileptiform activity on routine or ambulatory ictal EEG during a typical ictus/event in which the semiology would make ictal epileptiform EEG activity expected during equivalent epileptic seizures"2
In addition to meeting ILAE minimum requirements for FND-seiz diagnosis, must have previously undergone and documented in the electronic medical record a minimum of 24-hours of otherwise normal video EEG without interictal epileptiform findings
Duration of symptoms >3 months and continuing to experience NES at least monthly
Not currently undergoing any psychotherapeutic intervention, agree to forgo any psychotherapeutic intervention during the study, and if previously completed any psychotherapeutic intervention continue to experience monthly non-epileptic seizures

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If on psychotropic medications may choose to continue during the duration of the study at current doses, but consent to not modifying medication doses or switching to alternative psychotropic regimens during the trial
In good general health, as ascertained by medical history
Females of reproductive age (ages 18 to 50) must have a negative urine pregnancy test, performed onsite, and documented in the study record within 72 hours prior to the first TMS session

Who cannot join

History of clinical concern for concomitant epileptic seizures or epilepsy
History of ongoing psychosis, mania, active alcohol or substance use disorder as screened by the PSQ, YMRS, AUDIT, and DAST-10
History of positive screening urine test for drugs of abuse within the last year: cocaine, amphetamines, barbiturates, opiates
Active suicidal intent or a score >2 on question 3 of the HAM-D
Use of medications known to lower the seizure threshold at doses that may increase this risk in the setting of rTMS-iTBS (i.e. buproprion at >300 mg, combinations of tricyclic antidepressants, antipsychotics… as determined by investigators)
History of central nervous system surgeries or clinically relevant structural brain lesions

Show all 12Show fewer

Significant or unstable cardiac, metabolic, oncologic, psychiatric, developmental, or neurologic condition(s) or treatments that may impact safe participation in the study as determined by the study investigators (e.g. poorly-controlled heart failure, current or past cardiac arrhythmia, sustained systolic blood pressure >180, labile diabetes, significant electrolyte abnormality, brain cancer, cognitive impairment, neurodevelopmental disorders, autism spectrum disorder, mania, schizophrenia spectrum or other psychotic disorder, movement disorders, multiple sclerosis, moderate to severe brain injury)
Participation in any clinical trial with an investigational drug or device within the past month or concurrent to study participation
History of TMS exposure
TMS contraindications (e.g., ferromagnetic implants, cochlear implants, conditions or treat-ments that lower seizure threshold - as determined by study investigators).
Current pregnancy or desire to become pregnant during study duration without contraceptive plan
Are a prisoner or in police custody at the time of eligibility screening

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Recruitment Coordinator contact

(843) 637-1358

chasenj@musc.edu

United States1 site, 1 recruiting

Institute of Psychiatry, Brain Stimulation Department
Charleston, South Carolina, 29425
Joseph A Chasen, DO, 843-637-1358, chasenj@musc.edu
Joseph A Chasen, DO
Recruiting

Other trials in United States

About this study

Official title: Accelerated, Left Prefrontal Transcranial Magnetic Stimulation for Functional Seizures; An Open-Label Exploration of Feasibility, Tolerability, and Preliminary Efficacy

The purpose of this project is to assess the feasibility, tolerability, and preliminary efficacy of using an accelerated, intermittent theta burst stimulation (a-iTBS-rTMS) protocol targeting the left dorsolateral prefrontal cortex (l-dlPFC) for Psychogenic Non-Epileptic Seizures (PNES) or Seizure-Type Functional Neurologic Disorder (FND-seiz) in an open-label fashion. Following screening, consent, and enrollment, participants will receive 6-to-10 iTBS-rTMS sessions per day (i.e., theta burst; 600 pulses per session; 6000 pulses per day) over a 3-to-5 treatment days with a target of 30 total sessions (18,000 total pulses). TMS will be targeted to Beam F3 for comparison to the bulk of the literature and to most mimic replicable and clinical use. This proposed iTBS-rTMS protocol was chosen given its previously shown safety, tolerability, and effectiveness in other conditions, but also as it has the potential to shorten treatment to only 3 days, which investigators theorize will be more feasible for patients with FND-seiz.

Feasibility will be measured as the percentage of participants who receive at least 20 treatment sessions within the 3-to-5-day window. Other than self-assessments used in the safety screening process or to monitor TMS benefits and risks, secondary subjective measures will assess previously investigated FND-seiz-specific outcomes, which will be obtained prior to intervention and 4-weeks post-intervention. In addition to monthly seizure frequency, this will include validated measures regarding stigma, health-related QOL, depression, PTSD, somatic symptoms, psychosocial functioning, psychological distress, and clinical and participant impression of improvement and satisfaction. Sub-analysis will further divide participants with mild to no depression and/or PTSD versus moderate to severe depression and/or PTSD to further assess how the TMS effects known to effect other highly comorbid disorders with FND-seiz, may indirectly affect FND-seiz outcomes.

Read the detailed description

Seizure-Type Functional Neurologic Disorders (FND-seiz) are strikingly prevalent-accounting for 5-15% of epilepsy center referrals and up to 40% of epilepsy monitoring unit admissions-when considering the associated barriers to treatment and dismal outcomes. Due to resource-intensive requirements, diagnosis is often delayed by years. In the interim, patients frequently receive inappropriate antiseizure medications and have high utilization of emergency services. Years after diagnosis, many FND-seiz patients continue to experience non-epileptic seizures (NS) and have high rates of disability. Due to stigma and psychosocial barriers, engagement and responses to the standard of care, Cognitive Behavioral Therapy (CBT), are inconsistent. As many patients are told they may have epilepsy prior to receiving an accurate diagnosis, there is an obvious disconnect between the recommended psychological treatment and the physical nature of their symptoms, which can limit acceptance of the diagnosis and subsequently CBT engagement. Furthermore, the only powered RCT (the CODES trial) examining CBT in FND-seiz failed to show a significant seizure reduction at 12 months follow up and the overall effect size was lower than previously thought highlighting the limitations of a "one-size-fits-all" model for a highly comorbid disorder. Ultimately, patients with FND-seiz have been found to have a poorer overall quality of life compared to epilepsy and a standardized mortality rate 2.5 times greater the general population and comparable to that of drug-resistant epilepsy

Together these factors underscore the need for alternate treatments capable of addressing psychosocial challenges unique to FND-seiz or further investigating the underlying neurobiology. Investigators theorize that offering a brain-network based approach may reduce stigma associated with confusion over the "psychological" rather than "neurological" etiologic conception of FND-seiz, which if effective, may be a more feasible for some patients. Brain-imaging research and prior reports of benefit with neurostimulation suggests TMS to the left dorsolateral prefrontal cortex (l-dlPFC) has the potential to improve cortico-limbic or cortico-sensorimotor governance, which Investigators theorize in FND-seiz may decrease NS frequency or improve quality of life. Thus, Investigators aim to investigate the feasibility and tolerability of an accelerated, intermittent theta-burst TMS protocol in FND-seiz to best mimic current clinical trends and optimize TMS feasibility, which may have several applications for the FND-seiz population.

In clinical practice, the known, but rare risk of inducing an epileptic seizure with TMS and the difficulty differentiating epileptic from non-epileptic seizures, may decrease the comfort of TMS providers to use TMS in FND-seiz patients when indicated for other disabling disorders. In tandem with exploring the feasibility and tolerability of this intervention, Investigators hope to employ and investigate an informed safety protocol, with input from experts in the fields of epilepsy and brain stimulation. Helping providers safely screen patients, more decisively exclude patients with an inaccurate diagnosis or concomitant epilepsy and having a protocol to follow when treating FND-seiz patients who experience a NS during TMS stimulation may increase TMS access for FND-seiz patients with other TMS indications. Finally, as preliminary evidence here at MUSC also suggests combining TMS with CBT for other indications may have a synergistic effect and improve attrition with CBT, if TMS is preliminarily efficacious alone in FND-seiz specific outcomes in a small, open-label sample, this investigation may also help optimize future methodologies examining the use of TMS in FND-seiz.

Conditions: Functional Neurological Symptom Disorder, Functional Seizures
Being tested: Transcranial Magnetic Stimulation
Keywords: Mental Health, Psychiatry, Functional Seizures, Transcranial Magnetic Stimulation
Medical subject headings: Conversion Disorder, Psychogenic Nonepileptic Seizures, Psychological Well-Being

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Transcranial Magnetic StimulationDevice
Also called Accelerated TMS, Theta-burst TMS
Participants will receive 6 to 10 sessions per day (i.e., theta burst; 600 pulses per session; 6000 pulses per day) over 3 to 5 treatment days using a MagVenture MagPro TMS System. Treatment will consist of a total of 30 sessions (18,000 total pulses). A single session is defined as 600 pulses at 50 Hz for 2s (i.e., 5 Hz triplets) and repeated every 10s for a total of 190s per session to l-dlPFC at 120% rMT with 15-minute intersession intervals. TMS will be targeted to Beam F3 for comparison to the bulk of the literature and to most mimic replicable clinical use.

Study groups in NCT07059325
Study group	Role	What they receive
Interventional Arm	Experimental	Not described Receives: Device: Transcranial Magnetic Stimulation

What is being measured

The primary outcome is the main question the study is designed to answer.

Percentage of Participants Completing TMS Sessions
Description: Feasibility will be measured as the percentage of participants who complete at least 20 rTMS-iTBS treatment sessions within the 3-to-5-day treatment period.
Unit of Measure: Percentage (%) Time Frame: Assessed daily from Day 1 to Day 5 of the TMS treatment period and summarized at the 4-week follow-up visit.
Rationale: This measure focuses on the proportion of participants able to adhere to the intensive TMS protocol, a key indicator of feasibility. The time frame is now specific, covering the treatment days (Day 1 to Day 5) and the 4-week follow-up for final reporting.
Measured: Assessed daily from Day 1 to Day 5 of the TMS treatment period and summarized at the 4-week follow-up visit.
Session Delivery Patterns
Description: The number of total rTMS-iTBS sessions delivered will be recorded and analyzed to characterize protocol adherence and delivery patterns. rTMS-iTBS sessions within the protocol are aimed to be delivered over the 3-5 treatment days, during which participants may choose between 6-10 day treatment sessions per day if tolerable and feasible (total of 30 sessions to complete the rTMS-iTBS protocol) Unit of Measure: The number of sessions delivered, represented as a continuous, numerical value.
Rationale: This measure provides additional detail on how the protocol is implemented, addressing potential variability in session delivery to assess overall tolerability, feasibility, and analyze any potential adverse events. It further helps inform measures of efficacy if participants do not complete the total session target or complete the course of different time periods (ie, over 4-5 days or over 3 days).
Measured: Recorded daily from Day 1 to Day 5 of the TMS treatment period and summarized at the 4-week follow-up visit.
Adverse Event Rate
Description: Tolerability will be assessed by calculating the percentage of participants experiencing at least one adverse event (AE) related to the rTMS-iTBS protocol, such as headache, scalp discomfort, or dizziness. Adverse events will be recorded and classified using a standardized checklist based on common TMS-related side effects.
Unit of Measure: Percentage (%) of participants with at least one AE. Rationale: This measure quantifies the proportion of participants experiencing AEs, providing a clear indicator of the protocol's tolerability. Daily assessments during treatment capture immediate side effects, while the 4-week follow-up evaluates any delayed or persistent effects.
Measured: Assessed daily from Day 1 to Day 5 of the TMS treatment period, at the initial screening visit (baseline), and at the 4-week follow-up visit.
Serious Adverse Event Rate
Description: Serious adverse events (SAEs), defined as any event resulting in hospitalization, life-threatening conditions, or significant disability (e.g., seizure), will be tracked and reported as the percentage of participants experiencing at least one SAE related to the rTMS-iTBS protocol.
Unit of Measure: Percentage (%) of participants with at least one SAE. Rationale: This measure ensures monitoring of severe outcomes, which is critical for assessing the safety of the TMS protocol. The specific time points align with the study's schedule, ensuring comprehensive tracking of rare but serious events.
Measured: Assessed daily from Day 1 to Day 5 of the TMS treatment period, at the initial screening visit (baseline), and at the 4-week follow-up visit.
Pulses per Session Delivery Patterns
Description: The number and frequency of rTMS-iTBS pulses delivered over the 3-5 treatment days during which participants may choose between 6-10 day treatment sessions per day. This will be recorded and analyzed to characterize protocol adherence and delivery patterns. A pulse is defined as a burst of three magnetic pulses delivered in quick succession. One treatment session entails 190s encompassing 600 pulses per session. An intermittent theta-burst pulse is defined as a burst of three magnetic pulses delivered in quick succession. The end point of 30 treatment sessions is 18,000 total pulses delivered, which over the 3 to 5 day window can be achieved with 3,600 daily pulses for 5 days or up to 6,000 daily pulses over 3 days.
Unit of Measure: The number of sessions delivered, represented as a continuous, numerical value.
Rationale: This measure provides additional detail on how the protocol is implemented, addressing potential variability in session delivery to assess overall tole
Measured: Recorded daily from Day 1 to Day 5 of the TMS treatment period and summarized at the 4-week follow-up visit.

Secondary outcomes (11)

Non-epileptic Seizure Frequency (NES)
Participants will receive in-person and written documentation on how to document NES frequency (the number NES events over a 4 week period) following events ideally in tandem with a family or support persons who may live with them. The subject and their support person will be asked to document NES semiology, duration, and symptom severity to ensure the events in question are consistent with their known events that have been previously confirmed to represent NES with video EEG. Final analysis will represent a continuous variable comparing the numerical value (number of NES events over a 4 week period).
Measured: Assessed prior to intervention at visit 1, 2-4 weeks prior to starting the 3-5 day TMS treatment protocol, and at the final follow up visit 4 weeks after completing the TMS treatment protocol.
Chronic Illness Anticipated Stigma Scale (CIASS)
Purpose: Measures anticipated stigma related to chronic illness in participants with functional seizures.
Unit of Measure: Total score on a scale. Score Range: 12-60 (12 items, each scored 1-5). Type of Variable: Continuous (sum of item scores). Interpretation: Higher scores indicate greater anticipated stigma (worse outcome).
Measured: Assessed at initial visit (time point 0 at visit 1, 2-4 weeks pre-TMS) and at post-intervention follow-up (4 weeks post-TMS).
Montgomery-Asberg Depression Rating Scale (MADRS)
Purpose: Assesses depression severity in participants with functional seizures. Unit of Measure: Total score on a scale. Score Range: 0-60 (10 items, each scored 0-6). Type of Variable: Continuous (sum of item scores). Interpretation: Higher scores indicate greater depression severity (worse outcome).
Sub-analysis: Participants divided into mild/no depression (MADRS ≤ 20) vs. moderate/severe depression (MADRS > 20) to compare with FND-seizure-specific outcomes (e.g., NHS3, NES remission).
Measured: Assessed at initial visit (2-4 weeks pre-TMS) and follow-up (4 weeks post-TMS).
Post-Traumatic Stress Disorder Checklist for DSM-5 (PCL-5)
Purpose: Evaluates PTSD symptom severity in participants with functional seizures.
Unit of Measure: Total score on a scale. Score Range: 0-80 (20 items, each scored 0-4). Type of Variable: Continuous (sum of item scores). Interpretation: Higher scores indicate greater PTSD symptom severity (worse outcome).
Sub-analysis: Participants divided into mild/no depression (MADRS ≤ 20) vs. moderate/severe depression (MADRS > 20) and absent/mild PTSD (PCL-5 < 33) vs. moderate/extreme PTSD (PCL-5 ≥ 33) to compare with FND-seizure-specific outcomes.
Measured: Assessed at initial visit (2-4 weeks pre-TMS) and follow-up (4 weeks post-TMS).
PROMIS®-29+2 Profile v2.1 (PROPr)
Purpose: Measures health-related quality of life across multiple domains (physical function, anxiety, depression, fatigue, sleep disturbance, social function, pain intensity, pain interference).
Unit of Measure: T-scores for each domain. Score Range: T-scores (mean = 50, SD = 10) for each domain; typically ranges from 20-80 depending on the domain.
Type of Variable: Continuous (T-scores per domain).
Interpretation:
Physical function and social function: Higher scores indicate better outcomes. Anxiety, depression, fatigue, sleep disturbance, pain intensity, pain interference: Higher scores indicate worse outcomes.
Measured: Assessed at initial visit (2-4 weeks pre-TMS) and follow-up (4 weeks post-TMS).
Patient Health Questionnaire-15 (PHQ-15)
Purpose: Assesses somatic symptom severity in participants with functional seizures.
Unit of Measure: Total score on a scale. Score Range: 0-30 (15 items, each scored 0-2). Type of Variable: Continuous (sum of item scores). Interpretation: Higher scores indicate greater somatic symptom severity (worse outcome).
Measured: Assessed at initial visit (2-4 weeks pre-TMS) and follow-up (4 weeks post-TMS).
Clinical Outcomes in Routine Evaluation (CORE-10)
Purpose: Measures general psychological distress in participants with functional seizures.
Unit of Measure: Total score on a scale. Score Range: 0-40 (10 items, each scored 0-4). Type of Variable: Continuous (sum of item scores). Interpretation: Higher scores indicate greater psychological distress (worse outcome).
Measured: Assessed at initial visit (2-4 weeks pre-TMS) and follow-up (4 weeks post-TMS).
Clinical Global Impression-Improvement and Severity (CGI-I and CGI-S)
Purpose: Assesses clinical severity (CGI-S) and improvement (CGI-I) in participants' functional seizure condition.
Unit of Measure: Rating on a scale.
Score Range:
CGI-S: 1-7 (1 = normal, not at all ill; 7 = extremely ill). CGI-I: 1-7 (1 = very much improved; 7 = very much worse). Type of Variable: Ordinal (discrete ratings).
Interpretation:
CGI-S: Higher scores indicate greater illness severity (worse outcome). CGI-I: Higher scores indicate less improvement or worsening (worse outcome).
Measured: Time Frame: CGI-S assessed at initial visit (2-4 weeks pre-TMS) and follow-up (4 weeks post-TMS); CGI-I assessed only at follow-up (4 weeks post-TMS).
The National Hospital Seizure Severity Scale (NHS3)
Purpose: Measures seizure severity in participants with functional seizures. Unit of Measure: Total score on a scale. Score Range: 0-27 (based on seizure characteristics, e.g., frequency, duration, injury).
Type of Variable: Continuous (sum of weighted items). Interpretation: Higher scores indicate greater seizure severity (worse outcome).
Measured: Assessed at initial visit (2-4 weeks pre-TMS) and follow-up (4 weeks post-TMS).
Participants with Complete NES Remission
Purpose: Determines the proportion of participants achieving complete remission of non-epileptic seizures (NES).
Unit of Measure: Percentage of participants with no NES events. Score Range: Binary (0% or 100% remission per participant). Type of Variable: Binary (remission achieved or not). Interpretation: Achieving remission (100%) is a better outcome.
Measured: Assessed at follow-up (4 weeks post-TMS).
Participants with >50% Reduction in NES Frequency
Purpose: Measures the proportion of participants with a significant reduction (>50%) in non-epileptic seizure frequency.
Unit of Measure: Percentage of participants achieving >50% reduction in NES frequency.
Score Range: Binary (≥50% reduction or <50% reduction per participant). Type of Variable: Binary (reduction achieved or not). Interpretation: Achieving >50% reduction is a better outcome.
Measured: Assessed at follow-up (4 weeks post-TMS).

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

2 Sep 20251 Jul 2027

First posted10 Jul 2025
Study start2 Sep 2025
Primary completion2 Jan 2027 (estimated)
Study completion1 Jul 2027 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (26)Papers the sponsor has linked to this study.
Other trials for Functional Neurological Symptom DisorderStudies 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: Early Phase 1
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Model description: This is a single-arm open label investigation of the safety, feasibility, and tolerability of an accelerated TMS protocol in patients with Functional Seizures, also known as Psychogenic Non-Epileptic Seizures, with a secondary aim of examining preliminary efficacy.
Masking: None (open label)
Enrolment: 30 participants (estimated)

IDs, dates and publications

ClinicalTrials.gov ID: NCT07059325
Sponsor's protocol ID: Pro00144502
Acronym: FND-seiz
Status last verified: Sep 2026
First submitted: 16 Jun 2025
Last updated: 28 Sep 2026
Results posted: No
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: Yes
Individual data sharing: No: Other than demographics and rates of psychiatric comorbidity seen across participants that may effect results, as this is a psychiatrically vulnerable population, no IPD is planned to be shared.

Publications

Kan RLD, Padberg F, Giron CG, Lin TTZ, Zhang BBB, Brunoni AR, Kranz GS. Effects of repetitive transcranial magnetic stimulation of the left dorsolateral prefrontal cortex on symptom domains in neuropsychiatric disorders: a systematic review and cross-diagnostic meta-analysis. Lancet Psychiatry. 2023 Apr;10(4):252-259. doi: 10.1016/S2215-0366(23)00026-3. Epub 2023 Mar 7.
PubMed 36898403
Wang Y, Gao H, Qi M. Left dorsolateral prefrontal cortex activation can accelerate stress recovery: A repetitive transcranial stimulation study. Psychophysiology. 2023 Oct;60(10):e14352. doi: 10.1111/psyp.14352. Epub 2023 May 23.
PubMed 37221649
Philip NS, Barredo J, van 't Wout-Frank M, Tyrka AR, Price LH, Carpenter LL. Network Mechanisms of Clinical Response to Transcranial Magnetic Stimulation in Posttraumatic Stress Disorder and Major Depressive Disorder. Biol Psychiatry. 2018 Feb 1;83(3):263-272. doi: 10.1016/j.biopsych.2017.07.021. Epub 2017 Aug 8.
PubMed 28886760
Hassa T, Sebastian A, Liepert J, Weiller C, Schmidt R, Tuscher O. Symptom-specific amygdala hyperactivity modulates motor control network in conversion disorder. Neuroimage Clin. 2017 Apr 27;15:143-150. doi: 10.1016/j.nicl.2017.04.004. eCollection 2017.
PubMed 28529870
Maurer CW, LaFaver K, Ameli R, Epstein SA, Hallett M, Horovitz SG. Impaired self-agency in functional movement disorders: A resting-state fMRI study. Neurology. 2016 Aug 9;87(6):564-70. doi: 10.1212/WNL.0000000000002940. Epub 2016 Jul 6.
PubMed 27385746
Mcsweeney M, Reuber M, Levita L. Neuroimaging studies in patients with psychogenic non-epileptic seizures: A systematic meta-review. Neuroimage Clin. 2017 Jul 27;16:210-221. doi: 10.1016/j.nicl.2017.07.025. eCollection 2017.
PubMed 28808618
Perez DL, Dworetzky BA, Dickerson BC, Leung L, Cohn R, Baslet G, Silbersweig DA. An integrative neurocircuit perspective on psychogenic nonepileptic seizures and functional movement disorders: neural functional unawareness. Clin EEG Neurosci. 2015 Jan;46(1):4-15. doi: 10.1177/1550059414555905. Epub 2014 Nov 27.
PubMed 25432161
Perez DL, Nicholson TR, Asadi-Pooya AA, Begue I, Butler M, Carson AJ, David AS, Deeley Q, Diez I, Edwards MJ, Espay AJ, Gelauff JM, Hallett M, Horovitz SG, Jungilligens J, Kanaan RAA, Tijssen MAJ, Kozlowska K, LaFaver K, LaFrance WC Jr, Lidstone SC, Marapin RS, Maurer CW, Modirrousta M, Reinders AATS, Sojka P, Staab JP, Stone J, Szaflarski JP, Aybek S. Neuroimaging in Functional Neurological Disorder: State of the Field and Research Agenda. Neuroimage Clin. 2021;30:102623. doi: 10.1016/j.nicl.2021.102623. Epub 2021 Mar 11.
PubMed 34215138
Nightscales R, McCartney L, Auvrez C, Tao G, Barnard S, Malpas CB, Perucca P, McIntosh A, Chen Z, Sivathamboo S, Ignatiadis S, Jones S, Adams S, Cook MJ, Kwan P, Velakoulis D, D'Souza W, Berkovic SF, O'Brien TJ. Mortality in patients with psychogenic nonepileptic seizures. Neurology. 2020 Aug 11;95(6):e643-e652. doi: 10.1212/WNL.0000000000009855. Epub 2020 Jul 20.
PubMed 32690794
McLoughlin C, McWhirter L, Pisegna K, Tijssen MAJ, Tak LM, Carson A, Stone J. Stigma in functional neurological disorder (FND) - A systematic review. Clin Psychol Rev. 2024 Aug;112:102460. doi: 10.1016/j.cpr.2024.102460. Epub 2024 Jun 13.
PubMed 38905960
Robson C, Myers L, Pretorius C, Lian OS, Reuber M. Health related quality of life of people with non-epileptic seizures: The role of socio-demographic characteristics and stigma. Seizure. 2018 Feb;55:93-99. doi: 10.1016/j.seizure.2018.01.001. Epub 2018 Jan 12.
PubMed 29414141
Samuels T, Pretorius C. Healthcare providers' perspectives on stigma when working with people with functional seizures. Seizure. 2023 Nov;112:121-127. doi: 10.1016/j.seizure.2023.10.002. Epub 2023 Oct 1.
PubMed 37820427
Karterud HN, Otto Nakken K, Lossius MI, Tschamper M, Ingebrigtesen T, Henning O. Young people diagnosed with psychogenic nonepileptic seizures (PNES) years ago - How are they now? Epilepsy Behav. 2024 Aug;157:109874. doi: 10.1016/j.yebeh.2024.109874. Epub 2024 Jun 7.
PubMed 38851124
Abi-Nahed R, Li J, Carlier J, Birca V, Berube AA, Nguyen DK. Outcome of psychogenic non-epileptic seizures following diagnosis in the epilepsy monitoring unit. Front Neurol. 2024 Feb 14;15:1363459. doi: 10.3389/fneur.2024.1363459. eCollection 2024.
PubMed 38419704
Fettig M, El-Hage W, Klemina I, Biberon J, de Toffol B, Thiriaux A, Visseaux JF, Lemesle Martin M, Schwan R, Bechiri F, Cohn A, Meyer M, Maillard L, Hingray C. Adherence to mental health care and caregiver-patient relationship after diagnosis of psychogenic non-epileptic seizures: Longitudinal follow-up study. Seizure. 2020 Aug;80:227-233. doi: 10.1016/j.seizure.2020.06.001. Epub 2020 Jun 8.
PubMed 32659654

Interested in taking part?

Recruitment Coordinator

(843) 637-1358

chasenj@musc.edu

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 28 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Accelerated, Left Prefrontal Transcranial Magnetic Stimulation for Functional Seizures; An Open-Label Exploration of Feasibility, Tolerability, and Preliminary Efficacy
ClinicalTrials.gov ID: NCT07059325
Acronym / sponsor ID: FND-seiz / Pro00144502
Conditions: Functional Neurological Symptom Disorder, Functional Seizures
Keywords: Mental Health, Psychiatry, Functional Seizures, Transcranial Magnetic Stimulation
Phase: Early Phase 1
Study type: Interventional
Recruitment status: Recruiting
Enrolment: 30 participants (estimated)
Lead sponsor: Medical University of South CarolinaUniversity, hospital or other
Study start: 2 Sep 2025 (actual)
Primary completion: 2 Jan 2027 (estimated)
Study completion: 1 Jul 2027 (estimated)
First posted: 10 Jul 2025 (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.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1
Model description: This is a single-arm open label investigation of the safety, feasibility, and tolerability of an accelerated TMS protocol in patients with Functional Seizures, also known as Psychogenic Non-Epileptic Seizures, with a secondary aim of examining preliminary efficacy.

Arm	Type	Receives
Interventional Arm	Experimental	Device: Transcranial Magnetic Stimulation

Who may qualify

Ages: 18 to 65 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (9 listed)

>18 years old and <65 years old
English Speaking, can read and write, and able to provide informed consent
Diagnosis of "documented" Functional Seizures as made by an MUSC epileptologist or neurologist using the ILAE recommendations: "by clinician experienced in diagnosis of seizure disorders (on video or in person), showing semiology of typical of FND-seiz, while on EEG plus no epileptiform activity on routine or ambulatory ictal EEG during a typical ictus/event in which the semiology would make ictal epileptiform EEG activity expected during equivalent epileptic seizures"2
In addition to meeting ILAE minimum requirements for FND-seiz diagnosis, must have previously undergone and documented in the electronic medical record a minimum of 24-hours of otherwise normal video EEG without interictal epileptiform findings
Duration of symptoms >3 months and continuing to experience NES at least monthly

Key exclusion criteria (12 listed)

History of clinical concern for concomitant epileptic seizures or epilepsy
History of ongoing psychosis, mania, active alcohol or substance use disorder as screened by the PSQ, YMRS, AUDIT, and DAST-10
History of positive screening urine test for drugs of abuse within the last year: cocaine, amphetamines, barbiturates, opiates
Active suicidal intent or a score >2 on question 3 of the HAM-D
Use of medications known to lower the seizure threshold at doses that may increase this risk in the setting of rTMS-iTBS (i.e. buproprion at >300 mg, combinations of tricyclic antidepressants, antipsychotics… as determined by investigators)

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: Accelerated TMS, Theta-burst TMSParticipants will receive 6 to 10 sessions per day (i.e., theta burst; 600 pulses per session; 6000 pulses per day) over 3 to 5 treatment days using a MagVenture MagPro TMS System. Treatment will consist of a total of 30 sessions (18,000 total pulses). A single session is defined as 600 pulses at 50 Hz for 2s (i.e., 5 Hz triplets) and repeated every 10s for a total of 190s per session to l-dlPFC at 120% rMT with 15-minute intersession intervals. TMS will be targeted to Beam F3 for comparison to the bulk of the literature and to most mimic replicable clinical use.	Device	Interventional Arm

Primary outcome

Percentage of Participants Completing TMS Sessions
Time frame: Assessed daily from Day 1 to Day 5 of the TMS treatment period and summarized at the 4-week follow-up visit.
Description: Feasibility will be measured as the percentage of participants who complete at least 20 rTMS-iTBS treatment sessions within the 3-to-5-day treatment period. Unit of Measure: Percentage (%) Time Frame: Assessed daily from Day 1 to Day 5 of the TMS treatment period and summarized at the 4-week follow-up visit. Rationale: This measure focuses on the proportion of participants able to adhere to the intensive TMS protocol, a key indicator of feasibility. The time frame is now specific, covering the treatment days (Day 1 to Day 5) and the 4-week follow-up for final reporting.
Session Delivery Patterns
Time frame: Recorded daily from Day 1 to Day 5 of the TMS treatment period and summarized at the 4-week follow-up visit.
Description: The number of total rTMS-iTBS sessions delivered will be recorded and analyzed to characterize protocol adherence and delivery patterns. rTMS-iTBS sessions within the protocol are aimed to be delivered over the 3-5 treatment days, during which participants may choose between 6-10 day treatment sessions per day if tolerable and feasible (total of 30 sessions to complete the rTMS-iTBS protocol) Unit of Measure: The number of sessions delivered, represented as a continuous, numerical value. Rationale: This measure provides additional detail on how the protocol is implemented, addressing potential variability in session delivery to assess overall tolerability, feasibility, and analyze any potential adverse events. It further helps inform measures of efficacy if participants do not complete the total session target or complete the course of different time periods (ie, over 4-5 days or over 3 days).
Adverse Event Rate
Time frame: Assessed daily from Day 1 to Day 5 of the TMS treatment period, at the initial screening visit (baseline), and at the 4-week follow-up visit.
Description: Tolerability will be assessed by calculating the percentage of participants experiencing at least one adverse event (AE) related to the rTMS-iTBS protocol, such as headache, scalp discomfort, or dizziness. Adverse events will be recorded and classified using a standardized checklist based on common TMS-related side effects. Unit of Measure: Percentage (%) of participants with at least one AE. Rationale: This measure quantifies the proportion of participants experiencing AEs, providing a clear indicator of the protocol's tolerability. Daily assessments during treatment capture immediate side effects, while the 4-week follow-up evaluates any delayed or persistent effects.
Serious Adverse Event Rate
Time frame: Assessed daily from Day 1 to Day 5 of the TMS treatment period, at the initial screening visit (baseline), and at the 4-week follow-up visit.
Description: Serious adverse events (SAEs), defined as any event resulting in hospitalization, life-threatening conditions, or significant disability (e.g., seizure), will be tracked and reported as the percentage of participants experiencing at least one SAE related to the rTMS-iTBS protocol. Unit of Measure: Percentage (%) of participants with at least one SAE. Rationale: This measure ensures monitoring of severe outcomes, which is critical for assessing the safety of the TMS protocol. The specific time points align with the study's schedule, ensuring comprehensive tracking of rare but serious events.
Pulses per Session Delivery Patterns
Time frame: Recorded daily from Day 1 to Day 5 of the TMS treatment period and summarized at the 4-week follow-up visit.
Description: The number and frequency of rTMS-iTBS pulses delivered over the 3-5 treatment days during which participants may choose between 6-10 day treatment sessions per day. This will be recorded and analyzed to characterize protocol adherence and delivery patterns. A pulse is defined as a burst of three magnetic pulses delivered in quick succession. One treatment session entails 190s encompassing 600 pulses per session. An intermittent theta-burst pulse is defined as a burst of three magnetic pulses delivered in quick succession. The end point of 30 treatment sessions is 18,000 total pulses delivered, which over the 3 to 5 day window can be achieved with 3,600 daily pulses for 5 days or up to 6,000 daily pulses over 3 days. Unit of Measure: The number of sessions delivered, represented as a continuous, numerical value. Rationale: This measure provides additional detail on how the protocol is implemented, addressing potential variability in session delivery to assess overall tole

11 secondary outcomes

Non-epileptic Seizure Frequency (NES)
Time frame: Assessed prior to intervention at visit 1, 2-4 weeks prior to starting the 3-5 day TMS treatment protocol, and at the final follow up visit 4 weeks after completing the TMS treatment protocol.
Chronic Illness Anticipated Stigma Scale (CIASS)
Time frame: Assessed at initial visit (time point 0 at visit 1, 2-4 weeks pre-TMS) and at post-intervention follow-up (4 weeks post-TMS).
Montgomery-Asberg Depression Rating Scale (MADRS)
Time frame: Assessed at initial visit (2-4 weeks pre-TMS) and follow-up (4 weeks post-TMS).
Post-Traumatic Stress Disorder Checklist for DSM-5 (PCL-5)
Time frame: Assessed at initial visit (2-4 weeks pre-TMS) and follow-up (4 weeks post-TMS).
PROMIS®-29+2 Profile v2.1 (PROPr)
Time frame: Assessed at initial visit (2-4 weeks pre-TMS) and follow-up (4 weeks post-TMS).
Patient Health Questionnaire-15 (PHQ-15)
Time frame: Assessed at initial visit (2-4 weeks pre-TMS) and follow-up (4 weeks post-TMS).
Clinical Outcomes in Routine Evaluation (CORE-10)
Time frame: Assessed at initial visit (2-4 weeks pre-TMS) and follow-up (4 weeks post-TMS).
Clinical Global Impression-Improvement and Severity (CGI-I and CGI-S)
Time frame: Time Frame: CGI-S assessed at initial visit (2-4 weeks pre-TMS) and follow-up (4 weeks post-TMS); CGI-I assessed only at follow-up (4 weeks post-TMS).
The National Hospital Seizure Severity Scale (NHS3)
Time frame: Assessed at initial visit (2-4 weeks pre-TMS) and follow-up (4 weeks post-TMS).
Participants with Complete NES Remission
Time frame: Assessed at follow-up (4 weeks post-TMS).
Participants with >50% Reduction in NES Frequency
Time frame: Assessed at follow-up (4 weeks post-TMS).

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 28 Sep 2026.
Background: PubMed 36898403Kan RLD, Padberg F, Giron CG, Lin TTZ, Zhang BBB, Brunoni AR, Kranz GS. Effects of repetitive transcranial magnetic stimulation of the left dorsolateral prefrontal cortex on symptom domains in neuropsychiatric disorders: a systematic review and cross-diagnostic meta-analysis. Lancet Psychiatry. 2023 Apr;10(4):252-259. doi: 10.1016/S2215-0366(23)00026-3. Epub 2023 Mar 7.
Background: PubMed 37221649Wang Y, Gao H, Qi M. Left dorsolateral prefrontal cortex activation can accelerate stress recovery: A repetitive transcranial stimulation study. Psychophysiology. 2023 Oct;60(10):e14352. doi: 10.1111/psyp.14352. Epub 2023 May 23.
Background: PubMed 28886760Philip NS, Barredo J, van 't Wout-Frank M, Tyrka AR, Price LH, Carpenter LL. Network Mechanisms of Clinical Response to Transcranial Magnetic Stimulation in Posttraumatic Stress Disorder and Major Depressive Disorder. Biol Psychiatry. 2018 Feb 1;83(3):263-272. doi: 10.1016/j.biopsych.2017.07.021. Epub 2017 Aug 8.
Background: PubMed 28529870Hassa T, Sebastian A, Liepert J, Weiller C, Schmidt R, Tuscher O. Symptom-specific amygdala hyperactivity modulates motor control network in conversion disorder. Neuroimage Clin. 2017 Apr 27;15:143-150. doi: 10.1016/j.nicl.2017.04.004. eCollection 2017.
Background: PubMed 27385746Maurer CW, LaFaver K, Ameli R, Epstein SA, Hallett M, Horovitz SG. Impaired self-agency in functional movement disorders: A resting-state fMRI study. Neurology. 2016 Aug 9;87(6):564-70. doi: 10.1212/WNL.0000000000002940. Epub 2016 Jul 6.
Background: PubMed 28808618Mcsweeney M, Reuber M, Levita L. Neuroimaging studies in patients with psychogenic non-epileptic seizures: A systematic meta-review. Neuroimage Clin. 2017 Jul 27;16:210-221. doi: 10.1016/j.nicl.2017.07.025. eCollection 2017.
Background: PubMed 25432161Perez DL, Dworetzky BA, Dickerson BC, Leung L, Cohn R, Baslet G, Silbersweig DA. An integrative neurocircuit perspective on psychogenic nonepileptic seizures and functional movement disorders: neural functional unawareness. Clin EEG Neurosci. 2015 Jan;46(1):4-15. doi: 10.1177/1550059414555905. Epub 2014 Nov 27.
Background: PubMed 34215138Perez DL, Nicholson TR, Asadi-Pooya AA, Begue I, Butler M, Carson AJ, David AS, Deeley Q, Diez I, Edwards MJ, Espay AJ, Gelauff JM, Hallett M, Horovitz SG, Jungilligens J, Kanaan RAA, Tijssen MAJ, Kozlowska K, LaFaver K, LaFrance WC Jr, Lidstone SC, Marapin RS, Maurer CW, Modirrousta M, Reinders AATS, Sojka P, Staab JP, Stone J, Szaflarski JP, Aybek S. Neuroimaging in Functional Neurological Disorder: State of the Field and Research Agenda. Neuroimage Clin. 2021;30:102623. doi: 10.1016/j.nicl.2021.102623. Epub 2021 Mar 11.
Background: PubMed 32690794Nightscales R, McCartney L, Auvrez C, Tao G, Barnard S, Malpas CB, Perucca P, McIntosh A, Chen Z, Sivathamboo S, Ignatiadis S, Jones S, Adams S, Cook MJ, Kwan P, Velakoulis D, D'Souza W, Berkovic SF, O'Brien TJ. Mortality in patients with psychogenic nonepileptic seizures. Neurology. 2020 Aug 11;95(6):e643-e652. doi: 10.1212/WNL.0000000000009855. Epub 2020 Jul 20.
Background: PubMed 38905960McLoughlin C, McWhirter L, Pisegna K, Tijssen MAJ, Tak LM, Carson A, Stone J. Stigma in functional neurological disorder (FND) - A systematic review. Clin Psychol Rev. 2024 Aug;112:102460. doi: 10.1016/j.cpr.2024.102460. Epub 2024 Jun 13.
Background: PubMed 29414141Robson C, Myers L, Pretorius C, Lian OS, Reuber M. Health related quality of life of people with non-epileptic seizures: The role of socio-demographic characteristics and stigma. Seizure. 2018 Feb;55:93-99. doi: 10.1016/j.seizure.2018.01.001. Epub 2018 Jan 12.
Background: PubMed 37820427Samuels T, Pretorius C. Healthcare providers' perspectives on stigma when working with people with functional seizures. Seizure. 2023 Nov;112:121-127. doi: 10.1016/j.seizure.2023.10.002. Epub 2023 Oct 1.
Individual participant dataSharing planned: No. Other than demographics and rates of psychiatric comorbidity seen across participants that may effect results, as this is a psychiatrically vulnerable population, no IPD is planned to be shared.

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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.

Recruitment Coordinator contact

(843) 637-1358

chasenj@musc.edu

Joseph Chasen, DO principal investigator

Medical University of South Carolina

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

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 9 inclusion and 12 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 28 Sep 2026. 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.

What does this phase mean?

Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

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 Recruitment Coordinator ((843) 637-1358, chasenj@musc.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of Participants Completing TMS Sessions (time frame: Assessed daily from Day 1 to Day 5 of the TMS treatment period and summarized at the 4-week follow-up visit.). The study lists 5 primary outcomes in all. 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 NCT07059325, which also lists 26 linked publications.

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 28 Sep 2026.