Targeted Accelerated TMS for Post-Traumatic Stress Disorder

NCT07245641 | Recruiting FDA Device

• 1 other identifier: 2025P002359
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

Post-traumatic stress disorder (PTSD) is a highly prevalent and debilitating condition among veterans and active-duty military personnel, with rates as high as 30% in certain combat-exposed populations. Conventional treatments such as prolonged exposure therapy and pharmacotherapy have limited efficacy and high dropout rates, highlighting the need for novel, rapidly effective interventions. Transcranial magnetic stimulation (TMS) has been well established for treatment-resistant depression (TRD). Traditional TMS, which involves 6 to 7 weeks of daily, weekday scalp-targeted treatment, shows open-label response and remission rates of 58.1% and 30%, respectively. However, such protocols may be impractical for military personnel with limited medical leave. A new form of accelerated TMS (aTMS) that involves 10 imaging-guided treatments per day for 5 consecutive days has demonstrated substantial antidepressant benefits within days and response rates of 69% at 1-month follow-up. This protocol has not been tested for PTSD, in part because there was no causally informed brain circuit target. In this study, the investigators will test aTMS for PTSD using a novel PTSD circuit that the investigators have derived.

Conditions

Post Traumatic Stress Disorder (PTSD)

Keywords

Accelerated Transcranial Magnetic Stimulation; Post traumatic stress disorder; PTSD; TMS; Neuromodulation

Outcome Measures

Primary Outcomes (1)

• PTSD Checklist with Criterion A for DSM-5 (PCL-5)

  20 item PTSD scale, scored 0-80. Higher scores indicate worse symptoms. Investigators will use a repeated measures mixed model to examine the effect of treatment on PCL-5 scores over time as well as a group x time interaction not controlling for depression. Hypothesis: There will be a significant difference in PCL-5 score magnitude of change one month after treatment relative to baseline in the participants receiving active treatment vs. sham

  Before treatment to 1-month post treatment

Secondary Outcomes (1)

• PTSD Checklist with Criterion A for DSM-5 (PCL-5)

  Before treatment to 1-month post treatment

Other Outcomes (17)

• Clinician-Administered PTSD Scale for DSM-5 (CAP-5)

  Before treatment and 1 month after treatment

• Clinically Useful Anxiety Outcome Scale (CUXOS)

  Before treatment and daily for 5 treatment days

• Beck Depression Inventory (BDI)

  Before treatment, 1 week post treatment, and 1 month post treatment

Study Arms (2)

Active aiTBS

ACTIVE COMPARATOR

Participants in this group will receive active aiTBS with neuronavigation to a treatment target identified with individualized resting state functional connectivity.

Procedure: Transcranial Magnetic Stimulation

Sham aiTBS

SHAM COMPARATOR

Participants in this group will receive sham aiTBS with neuronavigation to a treatment target identified with individualized resting state functional connectivity. Participants in the sham group who continue to present with moderate PTSD symptoms (greater than or equal to 33 cutoff on PCL-5) at the post-treatment month 1 visit will be offered the opportunity to opt in and receive another course of active aTMS.

Procedure: Transcranial Magnetic Stimulation

Interventions

Transcranial Magnetic Stimulation PROCEDURE

Transcranial magnetic stimulation (TMS) is a focal, non-invasive form of brain stimulation that has FDA clearance for depression. In this study, a form of TMS called accelerated intermittent theta burst stimulation (aiTBS) will be administered under the supervision of a physician with TMS expertise.

Also known as: TMS, Accelerated intermittent theta burst stimulation, aiTBS

Active aiTBS; Sham aiTBS

Eligibility Criteria

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

You may qualify if:

• Age 18-65
• DSM-5 diagnosis of PTSD per PTSD Checklist for DSM-5 (CAPS-5)
• At least moderate symptoms of PTSD per PCL-5 (≥21)
• English proficiency sufficient to understand risks/benefits
• No new medications or medication increases before, during, or after aTMS
• Primary clinician (e.g. psychiatrist, therapist, psychologist, APRN, PA, etc.) responsible for psychiatric care before, during, and after the trial
• Agreement to lifestyle considerations:
• Abstain from becoming pregnant from screening to one-month after treatment (the MRI visit)
• Continue usual intake patterns of caffeine- or xanthine-containing products (e.g. coffee, tea, soft drinks, chocolate) throughout treatment
• No changes to routine intake of alcohol, tobacco, and recreational drugs if patients are using them at baseline for at least 24 hours before the start of each MRI and TMS session

Sponsors & Collaborators

• Brigham and Women's Hospital: lead
• Mass General Home Base Program: collaborator

Study Sites (1)

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

RECRUITING

Related Publications (6)

• Carpenter LL, Janicak PG, Aaronson ST, Boyadjis T, Brock DG, Cook IA, Dunner DL, Lanocha K, Solvason HB, Demitrack MA. Transcranial magnetic stimulation (TMS) for major depression: a multisite, naturalistic, observational study of acute treatment outcomes in clinical practice. Depress Anxiety. 2012 Jul;29(7):587-96. doi: 10.1002/da.21969. Epub 2012 Jun 11.

  PMID: 22689344 BACKGROUND

• Hoge CW, Castro CA, Messer SC, McGurk D, Cotting DI, Koffman RL. Combat duty in Iraq and Afghanistan, mental health problems, and barriers to care. N Engl J Med. 2004 Jul 1;351(1):13-22. doi: 10.1056/NEJMoa040603.

  PMID: 15229303 BACKGROUND

• Kessler RC, Sonnega A, Bromet E, Hughes M, Nelson CB. Posttraumatic stress disorder in the National Comorbidity Survey. Arch Gen Psychiatry. 1995 Dec;52(12):1048-60. doi: 10.1001/archpsyc.1995.03950240066012.

  PMID: 7492257 BACKGROUND

• Siddiqi SH, Philip NS, Palm ST, Carreon DM, Arulpragasam AR, Barredo J, Bouchard H, Ferguson MA, Grafman JH, Morey RA, Fox MD. A potential target for noninvasive neuromodulation of PTSD symptoms derived from focal brain lesions in veterans. Nat Neurosci. 2024 Nov;27(11):2231-2239. doi: 10.1038/s41593-024-01772-7. Epub 2024 Sep 24.

  PMID: 39317797 BACKGROUND

• Cole EJ, Stimpson KH, Bentzley BS, Gulser M, Cherian K, Tischler C, Nejad R, Pankow H, Choi E, Aaron H, Espil FM, Pannu J, Xiao X, Duvio D, Solvason HB, Hawkins J, Guerra A, Jo B, Raj KS, Phillips AL, Barmak F, Bishop JH, Coetzee JP, DeBattista C, Keller J, Schatzberg AF, Sudheimer KD, Williams NR. Stanford Accelerated Intelligent Neuromodulation Therapy for Treatment-Resistant Depression. Am J Psychiatry. 2020 Aug 1;177(8):716-726. doi: 10.1176/appi.ajp.2019.19070720. Epub 2020 Apr 7.

  PMID: 32252538 BACKGROUND

• Cole EJ, Phillips AL, Bentzley BS, Stimpson KH, Nejad R, Barmak F, Veerapal C, Khan N, Cherian K, Felber E, Brown R, Choi E, King S, Pankow H, Bishop JH, Azeez A, Coetzee J, Rapier R, Odenwald N, Carreon D, Hawkins J, Chang M, Keller J, Raj K, DeBattista C, Jo B, Espil FM, Schatzberg AF, Sudheimer KD, Williams NR. Stanford Neuromodulation Therapy (SNT): A Double-Blind Randomized Controlled Trial. Am J Psychiatry. 2022 Feb;179(2):132-141. doi: 10.1176/appi.ajp.2021.20101429. Epub 2021 Oct 29.

  PMID: 34711062 BACKGROUND

MeSH Terms

Conditions

Stress Disorders, Post-Traumatic

Interventions

Transcranial Magnetic Stimulation

Condition Hierarchy (Ancestors)

Stress Disorders, Traumatic; Trauma and Stressor Related Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Magnetic Field Therapy; Therapeutics

Central Study Contacts

Interventional Psychiatry Research Group

CONTACT

6175253526; bwhtap@mgb.org

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Participants will be randomized to receive either 1) active aTMS at their individualized target or 2) sham aTMS at their individualized target in a 2:1 randomization. One research assistant (RA) is the only individual unblinded in this study. The unblinded RA will have no other interactions with participants. RAs delivering treatment with stimulate participants with sham or active aTMS, with randomization assigned by the unblinded RA. Blind will be broken at 1-month follow-up visit for all participants, physicians, and treating technicians.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Director of TMS, Center for Brain Circuit Therapeutics

Model Details: Parallel-group double-blind randomized controlled trial

Study Record Dates

• First Submitted: November 14, 2025
• First Posted: November 24, 2025
• Study Start: December 15, 2025
• Primary Completion (Estimated): November 1, 2027
• Study Completion (Estimated): January 1, 2028
• Last Updated: February 2, 2026

Record last verified: 2026-01

Locations

US (1)