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

NCT ID: NCT03932773

Last Updated: 2025-08-22

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

330 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-05-01

Study Completion Date

2026-07-31

Brief Summary

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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.

Detailed Description

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Using three treatment arms, the study will examine Posttraumatic Stress Disorder (PTSD) symptom reduction when (1) 1 Hz (hertz) repetitive transcranial magnetic stimulation (rTMS) to the right dorsolateral prefrontal cortex (rDLPFC) is administered prior to each of 12 Cognitive Processing Therapy (CPT) sessions compared to when (2) sham rTMS is administered to the rDLPFC is administered prior to each of 12 CPT sessions and to when (3) 1 Hz rTMS is delivered to rDLPFC alone over 12 sessions.

Veterans with combat-related PTSD will be randomly assigned to one of the three treatment arms. Primary outcome PTSD symptom severity measures, secondary neuropsychological, electroencephalography (EEG), and magnetic resonance imaging (MRI) outcome measures, and prescreening assessments for study contraindicators will be collected prior to being assigned to a treatment arm (i.e., baseline).

Primary outcome PTSD symptom severity measures and secondary neuropsychological outcome measures will be collected twice within the span of the treatment sessions (i.e., sessions 5 and 9) and at three times following treatment competition (i.e., 1-month, 6-months, and 12-months). EEG also will be collected at the 1-month, 6-month, and 12-month assessments, and MRI will be collected at the 6-month and 12-month assessments.

Conditions

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Post Traumatic Stress Disorder

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

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.
Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Outcome Assessors
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.

Study Groups

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Sham rTMS + CPT

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

Group Type SHAM_COMPARATOR

Active rTMS

Intervention Type 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.

Cognitive Processing Therapy

Intervention Type 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.

Active rTMS + CPT

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

Group Type ACTIVE_COMPARATOR

Sham rTMS

Intervention Type 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.

Cognitive Processing Therapy

Intervention Type 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.

Active rTMS Alone

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

Group Type ACTIVE_COMPARATOR

Active rTMS

Intervention Type 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.

Interventions

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Active rTMS

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.

Intervention Type DEVICE

Sham rTMS

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.

Intervention Type DEVICE

Cognitive Processing Therapy

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.

Intervention Type BEHAVIORAL

Other Intervention Names

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1 Hz repetitive transcranial magnetic stimulation sham repetitive transcranial magnetic stimulation CPT

Eligibility Criteria

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Inclusion Criteria

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

Exclusion Criteria

* 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.
* history of seizures
* non-English speakers because not all of the screening forms, questionnaires, and tests are available in any language except for English
* cardiac pacemaker, implanted medication pumps of any sort that would increase the risk of rTMS
* any current medical condition that could preclude being able to safely participate in TMS treatment,
* use of prescription medication or illegal substances that lower the seizure threshold
* previous rTMS
Minimum Eligible Age

18 Years

Maximum Eligible Age

60 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of Texas Southwestern Medical Center

OTHER

Sponsor Role collaborator

Johns Hopkins University

OTHER

Sponsor Role collaborator

Metrocare Services of Dallas

UNKNOWN

Sponsor Role collaborator

Florida State University

OTHER

Sponsor Role collaborator

The University of Texas at Dallas

OTHER

Sponsor Role lead

Responsible Party

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John Hart, Jr.

Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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John Hart, Jr., MD

Role: PRINCIPAL_INVESTIGATOR

The University of Texas at Dallas

F. Andrew Kozel, MD

Role: PRINCIPAL_INVESTIGATOR

Florida State University, College of Medicine

John Burruss, MD

Role: PRINCIPAL_INVESTIGATOR

Metrocare Services of Dallas

Locations

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Florida State University College of Medicine

Tallahassee, Florida, United States

Site Status RECRUITING

Metrocare Services of Dallas

Addison, Texas, United States

Site Status RECRUITING

The University of Texas at Dallas

Dallas, Texas, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Elizabeth "Ellen" Morris, PhD

Role: CONTACT

214-883-3171

Jill Ritter, BS

Role: CONTACT

972-883-3171

Facility Contacts

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FSU Neuromodulation

Role: primary

850-644-2824

Steven A Cohen Military Family Clinic at Metrocare

Role: primary

469-680-3500

Celia Higginbotham

Role: primary

972-883-3171

Crista Thyvelikakath, MA

Role: backup

972-883-3171

References

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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.

Reference Type BACKGROUND
PMID: 28493729 (View on PubMed)

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.

Reference Type 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.

Reference Type BACKGROUND
PMID: 12946886 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 444788 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 3346454 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 29723024 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 24636739 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 1403624 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 17032094 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 21304137 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25222294 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 19773108 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22451240 (View on PubMed)

Other Identifiers

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CDMRP-BA160594

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

18-123

Identifier Type: -

Identifier Source: org_study_id

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