Accelerated TMS for Seizure-Type Functional Neurologic Disorders
Trial statusRecruiting
Trial phaseEarly Phase 1
Trial typeInterventional
Biological sexAll
Age18-65
SponsorMedical University of South Carolina
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
>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
Disqualifiers
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
Trial design
Design model
Single group
Treatments tested in this trial
Transcranial Magnetic Stimulation
DeviceParticipants 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.
Treatment groups
30 Participants
are divided into 1 treatment groupGroup A: Interventional ArmExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
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.2
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.3
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.4
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.Secondary outcomes
1
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.2
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).3
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).4
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).Sponsors and contacts
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Source ClinicalTrials.gov