RECONsolidation of Traumatic Memories to ResOLve Post Traumatic Stress Disorder (RECONTROLPTSD)

NCT03827057 | Completed Phase 2

• 1 other identifier: CNRM-83-9763
• Study Type: interventional
• Target: 94
• Locations: 1 country
• Sites: 1

Brief Summary

Posttraumatic Stress Disorder (PTSD) is a common cause of morbidity in combat veterans, but current treatments are often inadequate. Reconsolidation of Traumatic Memories (RTM) is a novel treatment that seeks to alter key aspects of the target memory (e.g., color, clarity, speed, distance, perspective) to make it less impactful, and reduce nightmares, flashbacks, and other features of PTSD. The memory is reviewed in the context of an imaginal movie theater, presenting a fast (\~45 sec) black and white movie of the trauma memory, with further adjustment as needed so the patient can comfortably watch it. Open and waitlist studies of RTM have reported high response rates and rapid remission, setting the stage for this randomized, controlled, single-blind trial comparing RTM versus prolonged exposure (PE), the PTSD therapy with the strongest current evidence base. The investigators hypothesize that RTM will be non-inferior to PE in reducing PTSD symptom severity post-treatment and at 1-year follow up; will achieve faster remission, with fewer dropouts; will improve cognitive function; and that epigenetic markers will correlate with treatment response. The investigators will randomize 108 active or retired service members (SMs) with PTSD to ≤10 sessions of RTM or PE, affording power to test our hypotheses while allowing for ≤ 25% dropouts. The investigators will use an intent to treat analysis, and the Clinician Administered PTSD Scale for the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition, or DSM5 (CAPS-5), conducted by blinded assessors, will be the primary outcome measure. Secondary measures of depression (PHQ-9), anxiety (GAD-7), sleep (PSQI), and functional status (WHOQOL-100), will be assessed pre- and post-treatment, and at 2, 6, and 12 months. ANOVA will compare symptom severity over time within and between groups. The investigators will track comorbid TBI, anticipating it will not adversely impact response. More effective therapies for PTSD, with and without TBI, must be developed and evaluated. RTM is safe and promising, but requires testing against evidence-based interventions in well-designed randomized clinical trials (RCTs). The full study can be conducted either in person or via secure video conferencing.

Conditions

Posttraumatic Stress Disorder; Traumatic Brain Injury

Keywords

posttraumatic stress disorder; traumatic brain injury; cognitive behavioral therapy; exposure therapy; reconsolidation

Outcome Measures

Primary Outcomes (1)

• Clinician Administered PTSD Symptom Scale for DSM5 (CAPS-5)

  the gold standard for PTSD diagnosis, a trained expert administrator scores PTSD symptom severity; range 0-80, higher score represents greater severity

  week 10

Secondary Outcomes (5)

• Change in Patient Health Questionnaire (PHQ-9) Score

  week 10, and 2, 6 and 12 months later, compared to baseline

• Change in PTSD Checklist for DSM5 (PCL5) Score

  week 10, and 2, 6 and 12 months later, compared to baseline

• Change in Pittsburgh Sleep Quality Index (PSQI) Score

  week 10, and 2, 6 and 12 months later, compared to baseline

• Change in Neurobehavioral Symptom Inventory (NSI) Score

  week 10, and 2, 6 and 12 months later, compared to baseline

• Change in World Health Organization Quality of Life Inventory (WHOQOL-100) Score

  week 10, and 2, 6 and 12 months later, compared to baseline

Study Arms (2)

Reconsolidation of Traumatic Memories (RTM)

EXPERIMENTAL

Participants in each arm of the study will receive up to 10 90-minute manualized treatment sessions. RTM will follow a manual developed by the Research and Recognition Project, who will also train and supervise the therapists. It is anticipated that these treatments will most often be administered once per week for 10 weeks. To best meet participant needs, we will allow therapy in either arm to be "massed" in the pattern recently reported by Foa et al. for PE, with sessions separated by at least 24 hours over two weeks. This schedule has been used with both RTM and PE without hurting response rates, and may reduce drop-out rates. Participants who achieve remission of their PTSD before 10 sessions, measured by a PCL5 \<34, can decide with their therapist whether early cessation of therapy is appropriate.

Behavioral: Reconsolidation of Traumatic Memories (RTM)

Prolonged Exposure (PE)

ACTIVE COMPARATOR

Participants in each arm of the study will receive up to 10 90-minute manualized treatment sessions. PE will follow a manual written by the Foa and colleagues, and the therapists will be trained by expert trainers from the Center for Deployment Psychology. It is anticipated that these treatments will most often be administered once per week for 10 weeks. To best meet participant needs, we will allow therapy in either arm to be "massed" in the pattern recently reported by Foa et al. for PE, with sessions separated by at least 24 hours over two weeks. This schedule has been used with both RTM and PE without hurting response rates, and may reduce drop-out rates. Participants who achieve remission of their PTSD before 10 sessions, measured by a PCL5 \<34, can decide with their therapist whether early cessation of therapy is appropriate.

Behavioral: Prolonged Exposure (PE)

Interventions

Reconsolidation of Traumatic Memories (RTM) BEHAVIORAL

RTM is a trauma-focused, but not cognitive behavioral, therapy: it involves brief exposure to the trauma memory, but does rely on conscious responses to correct the symptoms of PTSD. RTM was first used to treat phobias in the 1970s, and has more recently been refined to focus on reconsolidation to update long-term memories, reconfiguring the salience structure of the original memory, and incorporating those changes into the overall memory structure. Reconsolidation is a neural mechanism for updating long-term memory, inserting new information that contradicts an essential element of the memory, which makes it possible to change the emotional tone and salience of the memory. It is hypothesized that RTM can thereby achieve quicker, greater, and more durable responses than with "traditional" exposure therapies.

Reconsolidation of Traumatic Memories (RTM)

Prolonged Exposure (PE) BEHAVIORAL

PE is a trauma-focused cognitive behavioral therapy (TFCBT) that depends on exposure to the feared stimulus as a central effector of change, utilizing extinction, which theorizes that if a trigger that previously elicited a fear response is presented enough times without reinforcement, the response fades. Previous researchers have shown that extinction involves the creation of a new blocking memory which prevents expression of the original fear memory. While PE has more evidence to support its efficacy in PTSD than other approaches, and a majority achieve a clinical response (e.g., decrease in CAPS score of 10 or more), many do not achieve complete remission of symptoms, and the blocking memory may be fragile, so subsequent triggers may result in relapse.

Prolonged Exposure (PE)

Eligibility Criteria

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

You may qualify if:

• Meets criteria for PTSD on the CAPS5, with past month nightmares or flashbacks.
• Willing to be randomly assigned to one of the two interventions and to complete all study measures.
• Able to exhibit capacity to understand the informed consent process, by completion of a corresponding series of questions

You may not qualify if:

• \. history of psychosis, bipolar disorder, or active suicidal or homicidal ideation

Sponsors & Collaborators

• Uniformed Services University of the Health Sciences: lead
• Research and Recognition Project: collaborator

Study Sites (1)

Uniformed Services University of Health Sciences (USUHS)

Bethesda, Maryland, 20814, United States

Location

MeSH Terms

Conditions

Stress Disorders, Post-Traumatic; Brain Injuries, Traumatic

Condition Hierarchy (Ancestors)

Stress Disorders, Traumatic; Trauma and Stressor Related Disorders; Mental Disorders; Brain Injuries; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: CARE PROVIDER, OUTCOMES ASSESSOR
• Masking Details: The CAPS-5, the gold standard for PTSD diagnosis, will be administered and scored at baseline to confirm the diagnosis, and subsequently as the primary outcome measure at 2, 6, and 12 months, by expert administrators who will be blinded to treatment arm.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Model Details: This is an interventional randomized controlled trial in which participants have an equal chance of receiving either the current best-evidenced PTSD treatment, prolonged exposure, or a novel approach, reconsolidation of traumatic memories, that has the potential to achieve a more rapid, durable and greater overall response rate.

Study Record Dates

• First Submitted: January 4, 2019
• First Posted: February 1, 2019
• Study Start: June 12, 2019
• Primary Completion: April 30, 2024
• Study Completion: May 6, 2025
• Last Updated: July 15, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: CSR
• Time Frame: after study completion
• Access Criteria: Must have approved research protocol

Locations

US (1)