An interventional study of Accelerated functional-connectivity guided transcranial magnetic stimulation in PTSD - Post Traumatic Stress Disorder, sponsored by Cognitive FX. Recruiting at 1 site in United States. Open to participants aged 18 Years to 65 Years. Per ClinicalTrials.gov, last updated 2026-07-28.
Sponsored by Cognitive FX · Not applicable, Interventional, and Treatment
This study tests a new brain stimulation treatment for post-traumatic stress disorder (PTSD), a condition that affects millions after trauma, causing symptoms like flashbacks, avoidance, mood changes, and heightened alertness.
The investigators will enroll 15 adults (ages 18-65) with PTSD. First, participants get a brain scan (fMRI) to map their unique brain connections between areas involved in fear and control-the right amygdala (fear center) and right dorsolateral prefrontal cortex (control area). Using this personalized map, the investigators will apply accelerated transcranial magnetic stimulation (TMS), a safe, non-invasive method using magnetic pulses to adjust brain activity. Treatment lasts 5 days (10 short sessions daily, totaling 90,000 pulses) targeting the identified spot to strengthen control over fear responses.
The study checks if this approach is practical, safe (tracking side effects like headaches), and shows early signs of reducing PTSD symptoms (measured by questionnaires and interviews). Follow-up lasts 3 months, with repeat scans to see brain changes.
This study will see if personalized, fast-paced TMS targeting the disrupted fear-control brain circuit in PTSD can be feasible and safe, and preliminarily reduce symptoms by improving brain connectivity, potentially offering a quicker alternative to standard treatments.
This pilot study evaluates the feasibility, safety, and preliminary efficacy of functional magnetic resonance imaging (fMRI)-guided accelerated continuous theta burst stimulation (cTBS) targeting the right dorsolateral prefrontal cortex (rDLPFC) in adults with post-traumatic stress disorder (PTSD). PTSD is characterized by dysregulation in the fear circuitry, including amygdala hyperreactivity and impaired prefrontal regulation, leading to persistent symptoms despite standard treatments like trauma-focused psychotherapy or selective serotonin reuptake inhibitors, which achieve adequate response in only about 50% of patients.
The intervention leverages resting-state fMRI to identify individualized rDLPFC targets based on maximal positive functional connectivity to the right amygdala, addressing inter-individual variability in circuit topography (average 4.5 cm variation per recent literature). Imaging is acquired on a 1.5T scanner with T1-weighted structural (MPRAGE: TR=1645 ms, TE=3.8 ms, voxel=0.8 mm isotropic) and resting-state functional sequences (EPI: TR=2000 ms, TE=40 ms, voxel=3.75×3.75×4 mm, 900 volumes). Data processing via FSL includes motion correction, spatial smoothing (5 mm FWHM), bandpass filtering (0.01-0.1 Hz), and nuisance regression. The peak correlation voxel in the rDLPFC (Brodmann areas 8,9,10,46) serves as the target; fallback to MNI [40,28,44] if data quality fails.
Treatment employs an accelerated cTBS protocol over 5 consecutive days (50 sessions total: 10/day, 1,800 pulses/session, 90,000 pulses overall) using ANT Visor 2 neuronavigation for precise coil positioning. Each session delivers bursts of 3 pulses at 50 Hz, repeated at 5 Hz for 40 seconds (600 pulses/train), with 3 trains and 30-second inter-train intervals, at 65-80% resting motor threshold (determined via EMG over the first dorsal interosseous). Inter-session intervals are 50 minutes, with continuous monitoring for adverse events.
The single-arm, open-label design includes a screening/baseline phase (informed consent, medical history, safety screenings), baseline fMRI for targeting, treatment phase with daily safety checks, post-treatment assessments (within 48-72 hours), and follow-ups at 1 and 3 months. Total participant commitment is \~3.5 months. Pre- and post-treatment fMRI explores mechanistic changes in rDLPFC-amygdala connectivity (seed-to-seed Pearson correlation, Fisher z-transformed) and target shifts (Euclidean distance, component decomposition), correlating with clinical improvements.
This approach combines precision neuromodulation with accelerated delivery to reduce treatment burden (5 days vs. 4-6 weeks standard), building on meta-analyses showing moderate-to-large TMS effects in PTSD (SMD=1.02) and FDA-cleared neuroimaging-guided protocols like SAINT. The study aims to generate proof-of-concept data for larger randomized trials, focusing on circuit-specific modulation to enhance fear extinction and prefrontal control. Safety is prioritized with strict contraindication screening, real-time monitoring, and an independent safety monitor reviewing serious adverse events.
200 studies on the registry are indexed under Combat Disorders; 90 are open to participants now.
This study's planned enrollment of 15 is below the median of 72 across 167 interventional studies indexed under Combat Disorders.
Browse Combat Disorders studies →Cognitive FX is the lead sponsor of 2 studies on the registry; 1 is open to participants now.
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Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Participants must meet ALL of the following criteria:
Exclusion Criteria
Participants meeting ANY of the following criteria will be excluded:
TMS :
Conductive, ferromagnetic, or other magnetic-sensitive metals implanted in the head or within 30 cm of the TMS coil (excluding the mouth), including:
MRI Contraindications:
Psychiatric Exclusions:
Psychiatric hospitalization within past 3 months
Medical Exclusions:
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.
The American Psychiatric Association’s manual of mental health diagnoses. DSM-5 (2013, revised as DSM-5-TR in 2022) replaced DSM-IV, and some studies still name the older edition. “Meets DSM criteria for …” means diagnosed by that edition’s diagnostic criteria, usually by a clinician in an interview.
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.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
DSM diagnostic criteria
The American Psychiatric Association’s manual of mental health diagnoses. DSM-5 (2013, revised as DSM-5-TR in 2022) replaced DSM-IV, and some studies still name the older edition. “Meets DSM criteria for …” means diagnosed by that edition’s diagnostic criteria, usually by a clinician in an interview.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
This is a single-arm, open-label pilot study. All enrolled participants will receive active fMRI-guided accelerated cTBS treatment to the right dorsolateral prefrontal cortex (rDLPFC). The study includes a screening/baseline phase, a 5-day treatment phase, and a 3-month follow-up phase.
Device: Accelerated functional-connectivity guided transcranial magnetic stimulation
Resting state functional connectivity scanning will be used to identify the peak positive correlate of the right amygdala in the right dorsolateral prefrontal cortex. This target will be stimulated during 50 sessions over 5 days, 10 sessions per day. Each TMS session will consist of 3 trains of 600-pulse continuous theta burst stimulation (cTBS). Each train consists of 3-pulse 50-Hz bursts at 5-Hz for 40-second trains, with trains every 70 seconds. This stimulation will be applied at 80% of the patient's resting motor threshold. Target site will be identified using ANT Neuro Visor2 neuronavigation system.
PTSD Checklist for DSM-5 (PCL-5)
A change in PTSD severity will be measured via administration of the PDSD Checklist for DSM-5 (PCL-5). This is a 20-question Likert scale, with scores ranging from 0 to 80. Higher scores indicate stronger PTSD symptoms.
Time frame: Baseline, post-treatment 5 days, 1 month, 3 months
Clinician-Administered PTSD Scale for DSM-5 (CAPS-5)
The Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) is the gold-standard PTSD assessment. It is a 30-item structured interview that can assess PTSD symptoms over the past week, as well as make current or lifetime diagnoses of PTSD. We will measure change in CAPS-5 score between baseline and 5 days post-treatment.
Time frame: Baseline, post-treatment 5 days, 3 months
Beck Depression Inventory-II (BDI-II)
The Beck Depression Inventory-II (BDI-II) is a 21-question self-report survey measuring the severity of depression in adolescents and adults.
Time frame: Baseline, post-treatment 5 days, 1 month, 3 months
Patient Global Impression of Change (PGI-C)
7-point self-reported instrument that measures a patient's belief about the efficacy of a treatment
Time frame: Post-treatment 5 days, 3 months
Columbia-Suicide Severity Rating Scale (C-SSRS)
The Columbia Suicide Severity Rating Scale (C-SSRS) is a standardized clinical tool used to identify and assess the risk of suicide. It isn't scored with a single total number but by interpreting "Yes/No" answers to identify risk levels (low, moderate, high) and specific suicidal ideation/behavior categories, with positive answers to later questions (like intent, specific plans, or preparatory acts) indicating higher, immediate risk requiring urgent intervention.
Time frame: Baseline, treatment days 1, 2, 3, 4, and 5, post-treatment 5 days, 1 month, 3 months
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
Treatment-emergent adverse events (TEAEs) will be assessed from the first TMS session through 3 months post-treatment. TEAEs include any adverse event emerging or worsening after treatment onset. Monitored events include: Local effects: headache, scalp discomfort, tinnitus Neurological: seizure, syncope, facial twitching Psychiatric: PTSD exacerbation, suicidality (C-SSRS), mood changes Systemic: fatigue, dizziness Severity will be graded per CTCAE v5.0 (Grades 1-5) and causality rated by the principal investigator. Assessments occur at each treatment session, end of treatment, and at 1- and 3-month follow-ups. SAEs (including seizure or emergent suicidality) will be reported to the IRB within 24 hours. The DSMB will review safety data at pre-specified interim analyses.
Time frame: Treatment initiation through 3 months post-treatment (approx. 95 days total)
Plan to share: Yes — All individual participant data underlying the text, tables, figures, and appendices reported in this trial, after deidentification.
Supporting information: Study protocol, Statistical analysis plan, Informed consent form
Time frame: Beginning 3 months following publication. No end date.
Access criteria: Researchers who provide a methodologically sound proposal can access the data upon request via email to tms.info@cognitivefxusa.com
No publications or documents are linked to this record.
Start is estimated for Aug 2026; primary completion for Dec 2026, 4 months later.
Of 79 interventional studies with no phase under Combat Disorders, half reached primary completion within 25 months of starting (the median), counting those still running; a quarter within 12 and three quarters within 44. This study's planned 4 months is below that.
How these figures are worked out, and which studies are left out of them.
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