Rapid Treatment of PTSD With Accelerated Non-Invasive Brain Stimulation

This study will test the clinical efficacy of an accelerated TMS (accel-TMS) protocol that rapidly addresses PTSD symptoms with 1 week (25 sessions over 5 days) of condensed treatment.

Study Overview

• Status: Recruiting
• Conditions: Traumatic Brain Injury; Post Traumatic Stress Disorder
• Intervention / Treatment: Device: Cool B70 AP Coil - Active (dl-PFC); Device: Cool D-B80 AP Coil - Active (dm-PFC); Device: Cool B70 AP Coil- Sham (dl-PFC); Device: Cool D-B80 AP Coil - Sham (dm-PFC); Device: Cool B70 Treatment Coil - Active Only

Detailed Description

This study will have three phases: an acute phase (1 week of treatments), an extension phase (second week of treatments), and a long-term observational follow-up phase of 6 months.

The acute phase will be a three-arm randomized sham-controlled trial with: Arm 1 = active left dl-PFC accel-TMS; Arm 2 = active dm-PFC accel-TMS; and Arm 3 = sham accel-TMS (half with sham dl-PFC and half with sham dm-PFC coil positioning).

In the subsequent extension phase, all participants will receive active left dl-PFC accel-TMS. For the follow-up phase, clinical outcomes will be assessed at 1-month, 3-months, and 6-months. The primary outcome measure will be the CAPS-5.

A range of other secondary outcome measures will also be included.

• Study Type: Interventional
• Enrollment (Estimated): 132
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Isabelle M Taylor, MA; Phone Number: 850-644-2824; Email: fsun@fsu.edu
• Study Contact Backup: Name: Kevin A Johnson, PhD; Phone Number: 850-644-2824; Email: fsun@fsu.edu

Study Locations

• United States
  • Florida
    • Tallahassee, Florida, United States, 32306
      • Recruiting
      • Florida State University
      • Contact: Isabelle M Taylor, MA; Phone Number: 850-644-2824; Email: fsun@fsu.edu
      • Contact: Kevin A Johnson, PhD; Phone Number: 850-644-2824; Email: fsun@fsu.edu
      • Principal Investigator: Frank A Kozel, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion:

1. Adults age 18 years to 65 years old.
2. Meets DSM-5 criteria for PTSD with a PCL-5 score > 33
3. No changes in psychotropic medication (if taking psychotropic medication) and/or changes in supportive psychotherapy for 1 month prior to initial visit; and clinically appropriate to maintain stable treatment regimen for duration of trial.
4. Clinically competent to give informed written consent and ability to understand study procedures and to comply with them for the entire length of the study

Exclusion:

1. Medical contraindication for neuromodulation (e.g., ferrous metal in head, seizure disorder, brain tumor, stroke, aneurysm, multiple sclerosis, etc.).
2. Active substance use disorder in last 3 months or any current substance use that puts the participant at increased risk or significant impairment.
3. Dementia or other cognitive disorder making unable to engage in treatment.
4. Any history or diagnosis of Schizophrenia, Schizoaffective Disorder, Delusional Disorder or other psychotic illness that precludes safe participation in trial.
5. Suicidal risk that precludes safe participation defined as clinical impression that the participant is at significant risk for suicide.
6. OCD cannot be the primary disorder but can have OCD symptoms.
7. Inability to stop taking any medication that significantly lowers the seizure threshold (e.g., tricyclic antidepressants, clozapine, etc.)
8. Current, planned, or suspected pregnancy
9. Unstable medical conditions or any current medical condition that could preclude being able to safely participate in TMS treatment (e.g., unstable metabolic abnormality, unstable angina, etc.)
10. Severe Traumatic Brain Injury
11. We will exclude non-English speakers because of the need for rapid communication during the delivery of treatments.
12. Significant ongoing litigation or claims that impact research activities, as determined by the research study team. (Research may especially be impacted when mental health or pain is being evaluated for litigation or claims, such as civil and criminal cases, disability claims and worker's compensation).
13. Prior known active TMS of dorsolateral prefrontal cortex or dorsomedial prefrontal cortex or electroconvulsive therapy (ECT) -

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Arm 1: active left dl-PFC accel-TMS; Acute Phase: Eligible participants will be randomized into one of the three treatment groups: active left dl-PFC accel-TMS vs. active dm-PFC accel-TMS vs. sham dl-PFC/dm-PFC accel TMS	Device: Cool B70 AP Coil - Active (dl-PFC); One side of the coil is the active and the other is sham. The B70 AP coil will be positioned over the left dorsolateral prefrontal cortex (dl-PFC).
Active Comparator: Arm 2:active dm-PFC accel-TMS; Acute Phase: Eligible participants will be randomized into one of the three treatment groups: active left dl-PFC accel-TMS vs. active dm-PFC accel-TMS vs. sham dl-PFC/dm-PFC accel TMS	Device: Cool D-B80 AP Coil - Active (dm-PFC); One side of the coil is the active and the other is sham. The cool D-B80 AP coil will be positioned over the midline (bilateral) dorsal medial prefrontal cortex (dmPFC) using location 25.8% distance from nasion to inion.
Sham Comparator: Arm 3 - sham accel-TMS dl-PFC; Acute Phase: Eligible participants will be randomized into one of the three treatment groups: active left dl-PFC accel-TMS vs. active dm-PFC accel-TMS vs. sham dl-PFC/dm-PFC accel TMS	Device: Cool B70 AP Coil- Sham (dl-PFC); One side of the coil is the active and the other is sham. The B70 AP coil will be positioned over the left dorsolateral prefrontal cortex (dl-PFC).
Sham Comparator: Arm 4: sham accel -TMS dm-PFC; Acute Phase: Eligible participants will be randomized into one of the three treatment groups: active left dl-PFC accel-TMS vs. active dm-PFC accel-TMS vs. sham dl-PFC/dm-PFC accel TMS	Device: Cool D-B80 AP Coil - Sham (dm-PFC); One side of the coil is the active and the other is sham. The cool D-B80 AP coil will be positioned over the midline (bilateral) dorsal medial prefrontal cortex (dmPFC) using location 25.8% distance from nasion to inion.
Active Comparator: Arm 5; Extension phase, all participants will receive active left dl-PFC accel-TMS.	Device: Cool B70 Treatment Coil - Active Only; The treatment will be the same as the left dl-PFC accel-TMS dl-PFC except that the Cool B70 Treatment coil only has an active treatment coil.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinician-Administered PTSD Scale for DSM-V (CAPS-V) to determine left dl-PFC accel-TMS efficacy	CAPS-V is a 30-item clinical interview used to diagnose PTSD as well as monitor PTSD symptoms. Questions address the traumatic event(s), symptom duration, subjective distress, impact on functioning, dissociation, and symptom improvement since last evaluation. During the Acute Phase, CAPS-V will be used to determine the rapid efficacy of left dl-PFC accel-TMS compared to sham accel-TMS at approximately one-week post-treatment.	Assessment of symptoms during the preceding week.
Clinician-Administered PTSD Scale for DSM-V (CAPS-V) to determine dm-PFC accel-TMS efficacy	A 30-item clinical interview used to diagnose PTSD as well as monitor PTSD symptoms. Questions address the traumatic event(s), symptom duration, subjective distress, impact on functioning, dissociation, and symptom improvement since last evaluation. During the Acute Phase, CAPS-V will be used to determine the rapid efficacy of dm-PFC accel-TMS compared to sham accel-TMS at approximately one-week post-treatment	Assessment of symptoms during the preceding week.
Clinician-Administered PTSD Scale for DSM-V (CAPS-V) to determine superior symptom reduction	A 30-item clinical interview used to diagnose PTSD as well as monitor PTSD symptoms. Questions address the traumatic event(s), symptom duration, subjective distress, impact on functioning, dissociation, and symptom improvement since last evaluation. During the Extension Phase, CAPS-V will be used to determine whether an additional week of left dl-PFC accel-TMS provides superior reduction of PTSD symptoms compared to one week of left dl-PFC accel-TMS.	Assessment of symptoms during the preceding week.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinician-Administered PTSD Scale for DSM-V (CAPS-V) to characterize durability of accel-TMS effects	A 30-item clinical interview used to diagnose PTSD as well as monitor PTSD symptoms. Questions address the traumatic event(s), symptom duration, subjective distress, impact on functioning, dissociation, and symptom improvement since last evaluation. During Follow-Up Phase to characterize the durability of accel-TMS effects on PTSD symptoms at 1-month, 3-months, and 6-months post treatment.	Assessment of symptoms during the preceding week before each follow-up visit.
Clinician-Administered PTSD Scale for DSM-V (CAPS-V) to determine superior outcomes between active left dl-PFC and active dm-PFC accel-TMS	A 30-item clinical interview used to diagnose PTSD as well as monitor PTSD symptoms. Questions address the traumatic event(s), symptom duration, subjective distress, impact on functioning, dissociation, and symptom improvement since last evaluation. During the Acute Phase to determine whether active left dl-PFC or active dm-PFC accel-TMS produces superior outcomes for PTSD symptoms	Assessment of symptoms during the preceding week.
Clinician-Administered PTSD Scale for DSM-V (CAPS-V) to determine added benefit during Extension	A 30-item clinical interview used to diagnose PTSD as well as monitor PTSD symptoms. Questions address the traumatic event(s), symptom duration, subjective distress, impact on functioning, dissociation, and symptom improvement since last evaluation. During the Extension Phase to determine whether an additional week of open left dl-PFC accel-TMS will provide added benefit to those participants that received active dm-PFC accel-TMS (i.e., targeting 2 brain regions versus 1 brain region).	Assessment of symptoms during the preceding week.

Collaborators and Investigators

• Sponsor: Florida State University
• Collaborators: United States Department of Defense
• Investigators: Principal Investigator: Frank A Kozel, MD, Florida State University

Study record dates

Study Major Dates

• Study Start (Actual): November 6, 2024
• Primary Completion (Estimated): June 30, 2028
• Study Completion (Estimated): December 30, 2028

Study Registration Dates

• First Submitted: August 6, 2024
• First Submitted That Met QC Criteria: August 6, 2024
• First Posted (Actual): August 9, 2024

Study Record Updates

• Last Update Posted (Actual): May 20, 2026
• Last Update Submitted That Met QC Criteria: May 18, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: PTSD; Transcranial Magnetic Stimulation; TMS
• Additional Relevant MeSH Terms: Trauma and Stressor Related Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Mental Disorders; Wounds and Injuries; Craniocerebral Trauma; Trauma, Nervous System; Brain Injuries; Stress Disorders, Traumatic; Brain Injuries, Traumatic; Stress Disorders, Post-Traumatic
• Other Study ID Numbers: STUDY00005179; CDMRP-TP230396 (Other Grant/Funding Number: Department of Defense)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No