Accelerated TMS for Seizure-Type Functional Neurologic Disorders

NCT07059325 | Recruiting Early Phase 1 FDA Device

• 1 other identifier: Pro00144502
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Functional Neurological Symptom Disorder; Functional Seizures

Keywords

Mental Health; Psychiatry; Functional Seizures; Transcranial Magnetic Stimulation

Outcome Measures

Primary Outcomes (5)

• 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.

  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).

  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.

  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.

  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

  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)

  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)

  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)

  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)

  Assessed at initial visit (2-4 weeks pre-TMS) and follow-up (4 weeks post-TMS).

• PROMIS®-29+2 Profile v2.1 (PROPr)

  Assessed at initial visit (2-4 weeks pre-TMS) and follow-up (4 weeks post-TMS).

Study Arms (1)

Interventional Arm

EXPERIMENTAL

Device: Transcranial Magnetic Stimulation

Interventions

Transcranial Magnetic Stimulation DEVICE

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

Interventional Arm

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \>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
• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Medical University of South Carolina: lead

Study Sites (1)

Institute of Psychiatry, Brain Stimulation Department

Charleston, South Carolina, 29425, United States

RECRUITING

Related Publications (26)

• 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.

  PMID: 36898403 BACKGROUND

• 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.

  PMID: 37221649 BACKGROUND

• 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.

  PMID: 28886760 BACKGROUND

• 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.

  PMID: 28529870 BACKGROUND

• 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.

  PMID: 27385746 BACKGROUND

• 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.

  PMID: 28808618 BACKGROUND

• 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.

  PMID: 25432161 BACKGROUND

• 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.

  PMID: 34215138 BACKGROUND

• 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.

  PMID: 32690794 BACKGROUND

• 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.

  PMID: 38905960 BACKGROUND

• 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.

  PMID: 29414141 BACKGROUND

• 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.

  PMID: 37820427 BACKGROUND

• 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.

  PMID: 38851124 BACKGROUND

• 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.

  PMID: 38419704 BACKGROUND

• 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.

  PMID: 32659654 BACKGROUND

• Rush BK, Kim L, Savinoff S, Watson M, Strom L. Ask the Patient: Goals for Functional seizure treatment. Epilepsy Behav. 2024 Dec;161:110141. doi: 10.1016/j.yebeh.2024.110141. Epub 2024 Nov 13.

  PMID: 39541741 BACKGROUND

• Goldstein LH, Robinson EJ, Chalder T, Reuber M, Medford N, Stone J, Carson A, Moore M, Landau S. Six-month outcomes of the CODES randomised controlled trial of cognitive behavioural therapy for dissociative seizures: A secondary analysis. Seizure. 2022 Mar;96:128-136. doi: 10.1016/j.seizure.2022.01.016. Epub 2022 Jan 25.

  PMID: 35228117 BACKGROUND

• Goldstein LH, Robinson EJ, Mellers JDC, Stone J, Carson A, Reuber M, Medford N, McCrone P, Murray J, Richardson MP, Pilecka I, Eastwood C, Moore M, Mosweu I, Perdue I, Landau S, Chalder T; CODES study group. Cognitive behavioural therapy for adults with dissociative seizures (CODES): a pragmatic, multicentre, randomised controlled trial. Lancet Psychiatry. 2020 Jun;7(6):491-505. doi: 10.1016/S2215-0366(20)30128-0. Epub 2020 May 20.

  PMID: 32445688 BACKGROUND

• Dworetzky BA. Neglected patients, few treatments, and minimal evidence: the updated cochrane review on psychological and behavioral treatments for nonepileptic seizures. Epilepsy Curr. 2014 Nov-Dec;14(6):329-31. doi: 10.5698/1535-7597-14.6.329. No abstract available.

  PMID: 25678863 BACKGROUND

• Goldstein LH, Chalder T, Chigwedere C, Khondoker MR, Moriarty J, Toone BK, Mellers JD. Cognitive-behavioral therapy for psychogenic nonepileptic seizures: a pilot RCT. Neurology. 2010 Jun 15;74(24):1986-94. doi: 10.1212/WNL.0b013e3181e39658.

  PMID: 20548043 BACKGROUND

• Stephen CD, Fung V, Lungu CI, Espay AJ. Assessment of Emergency Department and Inpatient Use and Costs in Adult and Pediatric Functional Neurological Disorders. JAMA Neurol. 2021 Jan 1;78(1):88-101. doi: 10.1001/jamaneurol.2020.3753.

  PMID: 33104173 BACKGROUND

• Reuber M, Elger CE. Psychogenic nonepileptic seizures: review and update. Epilepsy Behav. 2003 Jun;4(3):205-16. doi: 10.1016/s1525-5050(03)00104-5.

  PMID: 12791321 BACKGROUND

• Kerr WT, Zhang X, Hill CE, Janio EA, Chau AM, Braesch CT, Le JM, Hori JM, Patel AB, Allas CH, Karimi AH, Dubey I, Sreenivasan SS, Gallardo NL, Bauirjan J, Hwang ES, Davis EC, D'Ambrosio SR, Al Banna M, Cho AY, Dewar SR, Engel J Jr, Feusner JD, Stern JM. Factors associated with delay to video-EEG in dissociative seizures. Seizure. 2021 Mar;86:155-160. doi: 10.1016/j.seizure.2021.02.018. Epub 2021 Feb 15.

  PMID: 33621828 BACKGROUND

• Kerr WT, Janio EA, Le JM, Hori JM, Patel AB, Gallardo NL, Bauirjan J, Chau AM, D'Ambrosio SR, Cho AY, Engel J Jr, Cohen MS, Stern JM. Diagnostic delay in psychogenic seizures and the association with anti-seizure medication trials. Seizure. 2016 Aug;40:123-6. doi: 10.1016/j.seizure.2016.06.015. Epub 2016 Jun 23.

  PMID: 27398686 BACKGROUND

• LaFrance WC Jr, Baker GA, Duncan R, Goldstein LH, Reuber M. Minimum requirements for the diagnosis of psychogenic nonepileptic seizures: a staged approach: a report from the International League Against Epilepsy Nonepileptic Seizures Task Force. Epilepsia. 2013 Nov;54(11):2005-18. doi: 10.1111/epi.12356. Epub 2013 Sep 20.

  PMID: 24111933 BACKGROUND

• Devinsky O, Gazzola D, LaFrance WC Jr. Differentiating between nonepileptic and epileptic seizures. Nat Rev Neurol. 2011 Apr;7(4):210-20. doi: 10.1038/nrneurol.2011.24. Epub 2011 Mar 8.

  PMID: 21386814 BACKGROUND

MeSH Terms

Conditions

Conversion Disorder; Psychogenic Nonepileptic Seizures; Psychological Well-Being

Interventions

Transcranial Magnetic Stimulation

Condition Hierarchy (Ancestors)

Somatoform Disorders; Mental Disorders; Seizures; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Personal Satisfaction; Behavior

Intervention Hierarchy (Ancestors)

Magnetic Field Therapy; Therapeutics

Study Officials

• Joseph Chasen, DO

  Medical University of South Carolina

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Recruitment Coordinator

CONTACT

(843) 637-1358; chasenj@musc.edu

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principle Investigator, Resident Physician, MUSC Departments of Psychiatry and Neurology

Model Details: 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.

Study Record Dates

• First Submitted: June 16, 2025
• First Posted: July 10, 2025
• Study Start: September 2, 2025
• Primary Completion (Estimated): September 2, 2026
• Study Completion (Estimated): July 1, 2027
• Last Updated: September 22, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)