Multi-site Confirmatory Efficacy Treatment Trial of Combat-related PTSD

NCT03932773 | Recruiting DMC FDA Device

• 2 other identifiers: 18-123CDMRP-BA160594
• Study Type: interventional
• Target: 330
• Locations: 1 country
• Sites: 3

Brief Summary

The purpose of this study is to examine the benefits of combining repetitive Transcranial Magnetic Stimulation (rTMS) coupled with Cognitive Processing Therapy (CPT) in treating combat-related Posttraumatic Stress Disorder (PTSD) symptoms. The study will also examine change in depression, psychosocial functioning, and neurophysiological (i.e., electroencephalography and magnetic resonance images) measures.

Conditions

Post Traumatic Stress Disorder

Keywords

PTSD; post-traumatic stress disorder; military-related PTSD; CPT; cognitive processing therapy; rTMS; repetitive transcranial magnetic stimulation; combat; combat-related PTSD

Outcome Measures

Primary Outcomes (1)

• Treatment group differences in change from baseline to 6-months post-treatment on the Clinician Administered Posttraumatic Stress Disorder Scale for Diagnostic and Statistical Manual of Mental Disorders (5th edition) (CAPS-5) Total Severity Score

  Evaluation of treatment group differences on the Clinician Administered Posttraumatic Stress Disorder Scale for Diagnostic and Statistical Manual of Mental Disorders (5th edition) (CAPS-5) Total Severity Score (20 item sum, range 0-80, higher score=greater severity) in change from baseline to 6 months after the 12-week interventions. Weathers, FW, Blake, DD, Schnurr, PP, Kaloupek, DG, Marx, BP, \& Keane, TM. The Clinician-Administered PTSD Scale for DSM-5 (CAPS-5). www.ptsd.va.gov: National Center for PTSD, 2013.

  Outcome measures will be measured twice over a period of 37 weeks: Baseline, 6-Month Post-Treatment

Secondary Outcomes (67)

• Treatment group differences in change from baseline to 1 month post-treatment on the Clinician Administered Posttraumatic Stress Disorder Scale for Diagnostic and Statistical Manual of Mental Disorders (5th edition) (CAPS-5) Total Severity Score

  Outcome measures will be measured twice over a period of 17 weeks: Baseline, 1-Month Post-Treatment

• Treatment group differences in change from baseline to 12 months post-treatment on the Clinician Administered Posttraumatic Stress Disorder Scale for Diagnostic and Statistical Manual of Mental Disorders (5th edition) (CAPS-5) Total Severity Score

  Outcome measures will be measured twice over a period of 61 weeks: Baseline, 12-Month Post-Treatment

• Treatment group differences in change from baseline to 1 month post-treatment on the Posttraumatic Stress Disorder Checklist for for Diagnostic and Statistical Manual of Mental Disorders (5th edition) (PCL-5) Total Severity Score

  Outcome measures will be measured twice over a period of 17 weeks: Baseline, 1-Month Post-Treatment

• Treatment group differences in change from baseline to 6 months post-treatment on the Posttraumatic Stress Disorder Checklist for for Diagnostic and Statistical Manual of Mental Disorders (5th edition) (PCL-5) Total Severity Score

  Outcome measures will be measured twice over a period of 37 weeks: Baseline, 6-Month Post-Treatment

• Treatment group differences in change from baseline to 12 months post-treatment on the Posttraumatic Stress Disorder Checklist for for Diagnostic and Statistical Manual of Mental Disorders (5th edition) (PCL-5) Total Severity Score

  Outcome measures will be measured twice over a period of 61 weeks: Baseline, 12-Month Post-Treatment

Study Arms (3)

Sham rTMS + CPT

SHAM COMPARATOR

30 minutes of sham repetitive transcranial magnetic stimulation (rTMS) to the right dorsolateral prefrontal cortex (rDLPFC) prior to each Cognitive Processing Therapy (CPT) session

Device: Active rTMS; Behavioral: Cognitive Processing Therapy

Active rTMS + CPT

ACTIVE COMPARATOR

30 minutes of 1 Hz rTMS to rDLPFC prior to each CPT session

Device: Sham rTMS; Behavioral: Cognitive Processing Therapy

Active rTMS Alone

ACTIVE COMPARATOR

30 minutes of 1 Hz rTMS to rDLPFC at 1 session per week over 12 weeks

Device: Active rTMS

Interventions

Active rTMS DEVICE

A Magstim Rapid2 Stimulator repetitive transcranial magnetic stimulation (rTMS) device will be used to deliver 1 hertz (Hz) stimulation to right dorsolateral prefrontal cortex (rDLPFC) at 110% of a participant's rTMS motor threshold. The device passes electric current through a coil generating an alternating magnetic field. When positioned over the skull, the changing magnetic field causes electromagnetic inducted current flow in brain regions subjacent to the coil. Magnetic pulses (1.5-2.0 Tesla) lasting 100-300 microseconds at 1 Hz will be used. Motor threshold will be defined by the TMS intensity to right motor region required to induce visually perceptible movement of the contralateral abductor pollicus brevis 50 percent of the time.

Also known as: 1 Hz repetitive transcranial magnetic stimulation

Active rTMS Alone; Sham rTMS + CPT

Sham rTMS DEVICE

A Magstim Rapid2 Stimulator repetitive transcranial magnetic stimulation (rTMS) device will be paired with sham coil. The sham coil will induce electrical current flow in the tissue above the skull but will not induce current flow in brain tissue. The sham coil will be placed over the right prefrontal scalp region to target current flow in rDLPFC. Magnetic pulses lasting for 100-300 microseconds at 1 Hz will be used. For consistency across the rTMS conditions, motor threshold in the sham condition also will be determined by positioning the active rTMS coil over the right motor region and identifying the stimulation intensity required to induce visually perceptible movement of the contralateral abductor pollicus brevis 50 percent of the time.

Also known as: sham repetitive transcranial magnetic stimulation

Active rTMS + CPT

Cognitive Processing Therapy BEHAVIORAL

Cognitive Processing Therapy (CPT) is an evidenced based, trauma-focused treatment for Posttraumatic Stress Disorder (PTSD). CPT is a recommended form of treatment in the Veterans Administration - Department of Defense Clinical Practice Guideline for PTSD. The CPT manual delineates the agenda for each of 12 sessions (60 minutes per session): 1) Introduction to CPT and Patient Education regarding PTSD, 2) Meaning of the Trauma, 3) Identification of Thoughts and Feelings related to the Trauma, 4) Remembering the Trauma, 5) Identification of Stuck points, 6) Challenging Questions about the Trauma, 7) Dysfunctional/Maladaptive Thinking patterns related to the Trauma, 8) Safety Issues, 9) Trust Issues, 10) Power and Control Issues, 11) Self-Esteem Issues, and 12) Intimacy Issues.

Also known as: CPT

Active rTMS + CPT; Sham rTMS + CPT

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Veterans of Post-9/11 military conflicts
• with diagnosis of PTSD based on CAPS-5 related to Post-9/11 military combat

You may not qualify if:

• current enrollment in an acute experimental treatment for PTSD or trauma-focused psychotherapy treatment
• PTSD-inducing trauma exposure occurring within the last 3 months prior to pre-enrollment evaluation
• history of epilepsy or seizure disorder, a history of major head trauma,
• any neurologic condition likely to increase risk of seizures,
• brain tumors,
• moderate to severe substance use disorder in last 3 months or any substance use that puts the participant at increased risk or significant impairment
• stroke, and blood vessel abnormalities in the brain,
• dementia,
• Parkinson's disease, Huntington's chorea, or multiple sclerosis
• a high suicide risk
• a lifetime history of psychotic disorder or bipolar disorder
• inability to stop taking any medication that significantly lowers the seizure threshold
• pregnant or nursing
• metal fragments in the head, or any metal objects in or near the head that cannot be safely removed
• We will screen for a history of traumatic brain injury and exclude potential participants from the study if they have a history of severe TBI or are at high risk for seizures.

Sponsors & Collaborators

• The University of Texas at Dallas: lead
• University of Texas Southwestern Medical Center: collaborator
• Johns Hopkins University: collaborator
• Metrocare Services of Dallas: collaborator
• Florida State University: collaborator

Study Sites (3)

Florida State University College of Medicine

Tallahassee, Florida, 32308, United States

RECRUITING

Metrocare Services of Dallas

Addison, Texas, 75001, United States

RECRUITING

The University of Texas at Dallas

Dallas, Texas, 75235, United States

RECRUITING

Related Publications (13)

• Weathers FW, Bovin MJ, Lee DJ, Sloan DM, Schnurr PP, Kaloupek DG, Keane TM, Marx BP. The Clinician-Administered PTSD Scale for DSM-5 (CAPS-5): Development and initial psychometric evaluation in military veterans. Psychol Assess. 2018 Mar;30(3):383-395. doi: 10.1037/pas0000486. Epub 2017 May 11.

  PMID: 28493729 BACKGROUND

• Weathers FW, Litz BT, Keane TM, Palmieri PA, Marx BP, Schnurr PP. The PTSD Checklist for DSM-5 (PCL-5). Scale available from the National Center for PTSD at www.ptsd.va.gov, 2013.

  BACKGROUND

• Rush AJ, Trivedi MH, Ibrahim HM, Carmody TJ, Arnow B, Klein DN, Markowitz JC, Ninan PT, Kornstein S, Manber R, Thase ME, Kocsis JH, Keller MB. The 16-Item Quick Inventory of Depressive Symptomatology (QIDS), clinician rating (QIDS-C), and self-report (QIDS-SR): a psychometric evaluation in patients with chronic major depression. Biol Psychiatry. 2003 Sep 1;54(5):573-83. doi: 10.1016/s0006-3223(02)01866-8.

  PMID: 12946886 BACKGROUND

• Montgomery SA, Asberg M. A new depression scale designed to be sensitive to change. Br J Psychiatry. 1979 Apr;134:382-9. doi: 10.1192/bjp.134.4.382.

  PMID: 444788 BACKGROUND

• Keane TM, Caddell JM, Taylor KL. Mississippi Scale for Combat-Related Posttraumatic Stress Disorder: three studies in reliability and validity. J Consult Clin Psychol. 1988 Feb;56(1):85-90. doi: 10.1037//0022-006x.56.1.85. No abstract available.

  PMID: 3346454 BACKGROUND

• Bovin MJ, Black SK, Rodriguez P, Lunney CA, Kleiman SE, Weathers FW, Schnurr PP, Spira J, Keane TM, Marx BP. Development and validation of a measure of PTSD-related psychosocial functional impairment: The Inventory of Psychosocial Functioning. Psychol Serv. 2018 May;15(2):216-229. doi: 10.1037/ser0000220.

  PMID: 29723024 BACKGROUND

• Cyders MA, Littlefield AK, Coffey S, Karyadi KA. Examination of a short English version of the UPPS-P Impulsive Behavior Scale. Addict Behav. 2014 Sep;39(9):1372-6. doi: 10.1016/j.addbeh.2014.02.013. Epub 2014 Mar 3.

  PMID: 24636739 BACKGROUND

• Buss AH, Perry M. The aggression questionnaire. J Pers Soc Psychol. 1992 Sep;63(3):452-9. doi: 10.1037//0022-3514.63.3.452.

  PMID: 1403624 BACKGROUND

• Monson CM, Schnurr PP, Resick PA, Friedman MJ, Young-Xu Y, Stevens SP. Cognitive processing therapy for veterans with military-related posttraumatic stress disorder. J Consult Clin Psychol. 2006 Oct;74(5):898-907. doi: 10.1037/0022-006X.74.5.898.

  PMID: 17032094 BACKGROUND

• Tillman GD, Kimbrell TA, Calley CS, Kraut MA, Freeman TW, Hart J Jr. Repetitive transcranial magnetic stimulation and threat memory: selective reduction of combat threat memory p300 response after right frontal-lobe stimulation. J Neuropsychiatry Clin Neurosci. 2011 Winter;23(1):40-7. doi: 10.1176/jnp.23.1.jnp40.

  PMID: 21304137 BACKGROUND

• DeLaRosa BL, Spence JS, Shakal SK, Motes MA, Calley CS, Calley VI, Hart J Jr, Kraut MA. Electrophysiological spatiotemporal dynamics during implicit visual threat processing. Brain Cogn. 2014 Nov;91:54-61. doi: 10.1016/j.bandc.2014.08.003. Epub 2014 Sep 15.

  PMID: 25222294 BACKGROUND

• Maguire MJ, Brier MR, Moore PS, Ferree TC, Ray D, Mostofsky S, Hart J Jr, Kraut MA. The influence of perceptual and semantic categorization on inhibitory processing as measured by the N2-P3 response. Brain Cogn. 2009 Dec;71(3):196-203. doi: 10.1016/j.bandc.2009.08.018. Epub 2009 Sep 20.

  PMID: 19773108 BACKGROUND

• Calley CS, Motes MA, Chiang HS, Buhl V, Spence JS, Abdi H, Anand R, Maguire M, Estevez L, Briggs R, Freeman T, Kraut MA, Hart J Jr. Threat as a feature in visual semantic object memory. Hum Brain Mapp. 2013 Aug;34(8):1946-55. doi: 10.1002/hbm.22039. Epub 2012 Mar 25.

  PMID: 22451240 BACKGROUND

MeSH Terms

Conditions

Stress Disorders, Post-Traumatic

Interventions

2-cyclohexylidenhydrazo-4-phenyl-thiazole

Condition Hierarchy (Ancestors)

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

Study Officials

• John Hart, Jr., MD

  The University of Texas at Dallas

  PRINCIPAL INVESTIGATOR

• F. Andrew Kozel, MD

  Florida State University, College of Medicine

  PRINCIPAL INVESTIGATOR

• John Burruss, MD

  Metrocare Services of Dallas

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Elizabeth "Ellen" Morris, PhD

CONTACT

214-883-3171; neurolab@utdallas.edu

Jill Ritter, BS

CONTACT

972-883-3171; neurolab@utdallas.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Masking Details: Cognitive Processing Therapists will be blind to the treatment arm to which the participants are assigned. Baseline and outcome measure neuropsychological assessments will be conducted by an independent, blinded evaluator who is not part of the treatment team. Electroencephalography and magnetic resonance imaging data will be collected by technicians who are blinded to the arm to which the participants are assigned. Technicians administering repetitive transcranial magnetic stimulation (rTMS) will be blind to whether they are using an active or sham coil and to the treatment arm to which the participants are assigned. The coils are identical and will be setup by a different technician. Participants assigned to the 1 Hz rTMS coupled with Cognitive Processing Therapy or sham rTMS coupled with CPT will be blind as to whether they are receiving active or sham rTMS. Participants receiving rTMS only will not be blind to their group assignment.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: Participants will be randomly assigned to one of three treatment arms: (1) 1 Hz (hertz) repetitive transcranial magnetic stimulation (rTMS) to the right dorsolateral prefrontal cortex (rDLPFC) coupled with Cognitive Processing Therapy (CPT), (2) sham rTMS coupled with CPT, or (3) 1 Hz rTMS to the rDLPFC alone.

Study Record Dates

• First Submitted: April 4, 2019
• First Posted: May 1, 2019
• Study Start: May 1, 2019
• Primary Completion (Estimated): July 31, 2026
• Study Completion (Estimated): July 31, 2026
• Last Updated: August 22, 2025

Record last verified: 2025-08

Locations

US (3)