rTMS-augmented Written Exposure Therapy for PTSD

NCT ID: NCT05149534

Last Updated: 2026-01-12

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

98 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-01-03

Study Completion Date

2027-01-29

Brief Summary

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Post-traumatic stress disorder (PTSD) is prevalent and represents a high healthcare burden among Veterans. Repetitive transcranial magnetic stimulation (rTMS) is a brain-based therapy that may be effective for treating PTSD. The theorized mechanism of rTMS is enhancement of emotional flexibility via the dorsolateral prefrontal cortex node of the brain's cognitive control network. Given this mechanism of action, adding rTMS to an evidence-based psychotherapy (EBP) for PTSD may enhance treatment effects. Written exposure therapy (WET) is a brief EBP for PTSD found to reduce attrition compared to lengthier first line treatments. In this study, the investigators will determine if active rTMS added to WET compared with sham rTMS added to WET results in improved PTSD outcomes. The investigators will also determine if emotional flexibility is a mechanism of symptom improvement. This work will improve upon PTSD intervention and inform the mechanism of treatment effectiveness for Veterans suffering from PTSD.

Detailed Description

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The overarching goal of this CDA-2 proposal is to use repetitive transcranial magnetic stimulation (rTMS) to augment effectiveness of written exposure therapy (WET), a narrative-based trauma exposure paradigm, in treating posttraumatic stress disorder (PTSD) and emotion dysregulation in Operations Enduring Freedom (OEF) and Iraqi Freedom (OIF) Veterans. As a clinical neuropsychologist with expertise in emotion regulation, Dr. Lantrip's long-term goal is to improve upon and develop effective interventions for trauma-related illness in Veterans by identifying and targeting behavioral and neural mechanisms.

OEF/OIF Veterans have experienced increased length and number of deployments, contributing to diagnosis of PTSD. rTMS is a brain-based therapy involving application of a repetitive, brief magnetic pulse to the scalp through an electromagnetic coil. rTMS applied to the dorsolateral prefrontal cortex (DLPFC) has efficacy in patients with treatment-resistant depression, and recent work has shown efficacy for treating PTSD. Standard rTMS treatments are stand-alone, though the unique properties of rTMS may make it more effective when added to a psychotherapy such as an evidence-based psychotherapy (EBP) for PTSD.

rTMS is theorized to act on the DLPFC node of the brain's cognitive control network (CCN) to improve emotion regulatory processes and facilitate reduction in affective symptoms. In support of this theory, studies have found that improvements in affective flexibility, upregulation of positive affect, and downregulation of attention to negative stimuli occur in task-based paradigms immediately following stimulation of the DLPFC with rTMS in a single-session. In addition, recent research has found that rTMS prior to cognitive processing therapy (CPT) in Veterans with PTSD is effective at improving PTSD outcomes compared to sham rTMS plus CPT, possibly through the regulatory mechanism of the CCN. Given these promising findings, further study into optimizing rTMS-augmented EBPs for PTSD is warranted.

There are limitations to both rTMS and first line EBPs for PTSD. One problem is high numbers of sessions needed for effective treatment (i.e. 20 sessions of rTMS and 12-18 sessions of EBPs) contributing to high attrition rates. A large multi-site study of VA patients in PTSD clinic found that just 2% of a sample of 1924 Veterans who had at least one session of EBP received an "adequate dose" of at least 8 sessions.12 A potential optimization for rTMS-augmented EBPs would be to reduce session number to improve retention. WET is a novel EBP for PTSD that is non-inferior to CPT in as few as 5 sessions. Using rTMS to augment WET in Veterans with PTSD is a crucial step in this line of inquiry.

This double-blind, Phase II randomized controlled trial will examine whether rTMS added to WET results in superior outcomes compared to sham rTMS added to WET (N=98 with women and men equally represented). The investigators will randomize 49 OEF/OIF Veterans with PTSD to undergo an active rTMS/WET treatment protocol versus 49 OEF/OIF Veterans given a sham rTMS/WET treatment.

Specific Aim 1: To compare PTSD outcomes of those who experience active rTMS/WET versus sham rTMS/WET. Hypothesis 1: Active rTMS added to WET will contribute to greater PTSD symptom reduction compared to sham rTMS added to WET in Veterans with PTSD.

Specific Aim 2a: If there is a treatment effect in Aim 1, determine if emotional flexibility mediates the rTMS/WET-PTSD relation. Aim 2b (exploratory): Determine if emotional flexibility has a unique mediating effect over cognitive flexibility. Hypothesis 2a: Significant reduction in PTSD symptoms will be partially mediated by emotional flexibility. Hypothesis 2b: Significant reduction in PTSD symptoms will be partially mediated by cognitive flexibility, but to a lesser extent than emotional flexibility.

This CDA-2 extends Dr. Lantrip's research integrating emotion regulation and neurostimulation to understand and improve upon treatment of PTSD in Veterans. The CDA-2 will provide her with specialized training in WET, a unique exposure-based therapy for the treatment of trauma, as well as clinical trials for PTSD, and neurostimulation. The mentoring team integrates expertise in the proposed areas of study and extensive experience mentoring early career investigators. Project findings will inform a future VA Merit proposal, which will focus on individual differences and mechanisms contributing to PTSD symptom improvement in TMS-augmented behavioral therapy. This study has the potential to inform and improve upon existing treatments for PTSD. Together, Dr. Lantrip's work aligns with VA's priorities, CR\&D's mission, and with the goal to provide the highest quality of care for Veterans.

Conditions

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Post Traumatic Stress Disorder

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Double blind, randomized clinical trial
Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors
Participants deemed eligible after the baseline assessments will be randomized using a computerized block randomization with a 1:1 allocation ratio of active rTMS/WET and sham rTMS/WET conditions. The investigators will be utilizing permuted block design with randomized blocks of 4 and 2. This will be conducted by an independent study coordinator who will be uninvolved in the research beyond randomization and blinding with assistance from a data analyst in addition to statistics consultant.

Study Groups

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Active TMS/WET

Active repetitive transcranial magnetic stimulation completed prior to written exposure therapy

Group Type EXPERIMENTAL

Written Exposure Therapy

Intervention Type BEHAVIORAL

Narrative written disclosure of trauma administered in an evidence-based protocol.

repetitive transcranial magnetic stimulation

Intervention Type DEVICE

Noninvasive magnetic neuromodulation device

Sham TMS/WET

Sham repetitive transcranial magnetic stimulation completed prior to written exposure therapy

Group Type SHAM_COMPARATOR

Written Exposure Therapy

Intervention Type BEHAVIORAL

Narrative written disclosure of trauma administered in an evidence-based protocol.

repetitive transcranial magnetic stimulation

Intervention Type DEVICE

Noninvasive magnetic neuromodulation device

Interventions

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Written Exposure Therapy

Narrative written disclosure of trauma administered in an evidence-based protocol.

Intervention Type BEHAVIORAL

repetitive transcranial magnetic stimulation

Noninvasive magnetic neuromodulation device

Intervention Type DEVICE

Other Intervention Names

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WET rTMS

Eligibility Criteria

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Inclusion Criteria

-All veterans are eligible to be included in the study if they meet all the following criteria:

* veteran;
* English-speaking and able to provide written informed consent;
* diagnosed with PTSD;
* between the ages of 18 and 60 years. Participants over age 60 will not be included, as aging is known to impact brain structure, and thus the potential accuracy of the rTMS target, independently of PTSD.

Exclusion Criteria

* Individuals with history of seizures or other serious neurological history including acquired, developmental or degenerative neurologic illness, identified through medical chart review, will be excluded due to potential lowered threshold for seizures during rTMS stimulation.
* The effects of rTMS are unknown on fetal development, therefore, women who are pregnant will be excluded.
* Participants will also be screened and excluded if any of the following are met:

* current psychosis including psychotic disorder,
* bipolar disorder,
* schizophrenia; or another severe cognitive or psychiatric disorder;
* positive screen for current suicidal intent and plan \[with a score of 2 or 3 on BDI-2 item 9\];
* current substance use disorder; or substance use in the last 12 hours before the rTMS session.
* The investigators note that PTSD is often comorbid with traumatic brain injury (TBI) in military veterans who were deployed to a war zone. The investigators will use the Department of Defense and Veterans Affairs consensus-based classification of TBI severity for classification of TBI.
* Participants with moderate or severe TBI will be excluded.
* Participants with mild traumatic brain injury (mTBI) or concussion will be enrolled. This will enhance the ecological validity of the study.
* Participants with cognitive impairment as evidenced by a Montreal Cognitive Screen (MoCA) less than 23/30 or estimated baseline intellectual ability of a standard score of less than 80 on a word reading test will be excluded due to potential neurocognitive differences.
* Participants on psychotropic medications will not be excluded, but participants will be required to be stable on their medication for at least four weeks prior to beginning the study and throughout the time of study.
* Participants enrolled in long term, supportive psychotherapy (i.e. not an evidence-based psychotherapy (EBP)) may continue to be involved in their treatment throughout the study. However, participants involved in a concurrent EBPs will be excluded. Participants will be asked to disclose whether they chose to participate in an EBP during the course of the treatment or followup phases of the study.
Minimum Eligible Age

18 Years

Maximum Eligible Age

60 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Center for PTSD

FED

Sponsor Role collaborator

VA Office of Research and Development

FED

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Crystal M Lantrip

Role: PRINCIPAL_INVESTIGATOR

Central Texas Veterans Health Care System, Temple, TX

Locations

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Central Texas Veterans Health Care System, Temple, TX

Temple, Texas, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Crystal M Lantrip

Role: CONTACT

(254) 297-5155

Facility Contacts

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Joseph F Maher

Role: primary

254-743-1478

David E Dostal, PhD MA BS

Role: backup

(254) 743-2464 ext. 42464

Other Identifiers

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1IK2CX002101-01A2

Identifier Type: NIH

Identifier Source: secondary_id

View Link

MHBP-007-20F

Identifier Type: -

Identifier Source: org_study_id

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