An Early Phase 1 interventional study of Transcranial Magnetic Stimulation in Functional Neurological Symptom Disorder and Functional Seizures, sponsored by Medical University of South Carolina. Recruiting at 1 site in United States. Open to participants aged 18 Years to 65 Years. Per ClinicalTrials.gov, last updated 2026-09-28.
Sponsored by Medical University of South Carolina · Early Phase 1, Interventional, and Treatment
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.
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.
89 studies on the registry are indexed under Conversion Disorder; 34 are open to participants now.
This study's planned enrollment of 30 is below the median of 38 across 51 interventional studies indexed under Conversion Disorder.
Browse Conversion Disorder studies →Medical University of South Carolina is the lead sponsor of 874 studies on the registry; 166 are open to participants now.
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Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
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Clinically significant
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Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
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Contraindication
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Contraception
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Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
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Device: Transcranial Magnetic Stimulation
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.
Also known as: Accelerated TMS, Theta-burst TMS
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.
Time frame: 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).
Time frame: 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.
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.
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.
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.
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
Time frame: Recorded daily from Day 1 to Day 5 of the TMS treatment period and summarized at the 4-week follow-up visit.
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).
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)
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).
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)
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).
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)
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.
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)
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.
Time frame: 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).
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)
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).
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)
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).
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)
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).
Time frame: 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.
Time frame: 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.
Time frame: Assessed at follow-up (4 weeks post-TMS).
Plan to share: 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.
From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
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