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

Summary

Participation Requirements

Description

Primary Objective: The primary intent of this study is to determine whether Reconsolidation of Traumatic Memories (RTM) achieves a greater and/or more rapid response than prolonged exposure (PE) in the treatment of military service members with PTSD. This is an interventional randomized controlled t...

Primary Objective: The primary intent of this study is to determine whether Reconsolidation of Traumatic Memories (RTM) achieves a greater and/or more rapid response than prolonged exposure (PE) in the treatment of military service members with PTSD. This is an interventional randomized controlled trial in which all participants will receive active psychotherapy for PTSD, either what is currently considered the best-evidenced treatment, prolonged exposure, or a novel approach, reconsolidation of traumatic memories, that the investigators believe can achieve a higher response rate that will also prove more rapid and more durable. Participants will be active duty, reserve or National Guard service members, or former service members who were retired either medically or for length of service, who are eligible for care in the Department of Defense Healthcare System. Our findings should be generalizable to current and former military service members with PTSD. Approach This is a randomized controlled trial, enrolling 108 SMs with active PTSD, to RTM and PE, with up to 10 treatment sessions in each arm. The anticipated average enrollment rate will be 2 new participants per week. Participants may be male and female adult (ages 18+) participants who are active, reserve component, National Guard, or retired SMs; those with active suicidal or homicidal ideation, or a history of a psychotic disorder, will be excluded. Participants may have a history of lifetime mild or moderate traumatic brain injury (TBI), or no TBI history, but no lifetime history of severe TBI. Given that most participants are expected to be referred from the Center for Neuroscience and Regenerative Medicine (CNRM)'s Military Recruitment Protocol, it is anticipated that the great majority will have comorbid mild TBI (mTBI). All participants will also complete a total of 5 assessment visits: at baseline, immediately after the course of treatment, and at 2, 6 and 12 months. The baseline visit will begin with the completion of informed consent, followed by the administration of a series of questionnaires, a detailed neurocognitive assessment, and a blood draw; serial assessment will occur throughout the intervention period and for 12 months of follow-up. Participants will be randomly assigned to PE or RTM using a random number generator in MS Excel or other program to generate a random sequence of 108 zeroes and ones as a list. Subjects will be assigned to the treatment arms from that list: all zeros will be assigned to RTM and ones to PE. Hypotheses: Military service members with PTSD who are randomized to Reconsolidation of Traumatic Memories (RTM) therapy will be significantly more likely to achieve PTSD resolution than those randomized to Prolonged Exposure (PE) therapy, measured by the Clinician-Administered PTSD Scale for DSM5 (CAPS-5, by expert assessors blinded to treatment group assignment). The investigators also anticipate that RTM will achieve a response more rapidly, and will prove more durable. Among the secondary measures that will correlate with response to therapy are epigenetic changes, inflammatory biomarkers, neurocognitive function, and measures of depression, anxiety, sleep quality, and overall functional status. Primary Aim: Compare response rates of PTSD to RTM vs. PE, defined by remission of diagnosis on the CAPS-5, using a 2-tailed t-test, from baseline to post-intervention. The investigators will also utilize repeated measures ANOVA to compare CAPS-5 scores at baseline, post-intervention, and at 2-, 6-, and 12-month follow up within groups. In addition to this primary measure, the investigators will also use independent sample t-tests to document the efficacy of randomization by comparing the two groups' baseline CAPS-5 total scores, along with PCL5, PHQ-9, NSI, GAD-7, PSQI, WHOQOL-10, NIH-Toolbox Neurocognitive Assessment Composite Score, biomarker levels, number of TBIs, and all other demographic variables. Secondary Aim 1: Corroborate impact on PTSD symptom severity by measuring changes in CAPS-5 and PCL5, respectively, from baseline to post-treatment for RTM and PE, using a 2-tailed t-test. The investigators will then use repeated measures ANOVA to compare within and between group changes in the CAPS-5 at baseline, post-treatment, 2-, 6-, and 12-month follow-up for the CAPS-5, and these as well as scores obtained prior to treatment sessions 2, 4, 6, 8 and 10 for the PCL5. Secondary Aim 2: Compare rapidity of improvement in PTSD symptom severity between RTM and PE, measured by PCL5 scores at baseline, prior to treatment sessions 2, 4, 6, 8 and 10, and post-treatment, using a log-rank test to compare Kaplan-Meier curves for two groups. Secondary Aim 3: Compare the durability of response to treatment, with the primary measure being the percentage meeting criteria for PTSD on the CAPS-5, at post-treatment, and at 2-, 6-, and 12-month follow-ups, using repeated measures ANOVA between the two groups. The investigators will also determine whether this is corroborated by symptom severity reduction by comparing the CAPS-5 and PCL5 scores at these time points, again using repeated measures ANOVA. Secondary Aim 4: Compare the impact of RTM and PE upon comorbid conditions by using ANOVA with Bonferroni adjustment for multiple comparisons, to compare scores at baseline, post-treatment, and each of the follow-up time-points, on postconcussive symptoms (NSl), depression (PHQ-9), anxiety (GAD-7), sleep (PSQI), and functional status (WHOQOL-100). Secondary Aim 5: Compare key biomarker responses between RTM and PE. Cytokine concentrations (IL-6, IL-10, TNF) and DNA methylation rates with ANOVA with Bonferroni adjustment for multiple comparisons. The investigators will also conduct exploratory analyses to determine whether there are particular biomarkers that appear to be associated with response to the intervention, as opposed to nonresponse, within and across treatment groups. Secondary Aim 6: Compare neurocognitive function in response RTM and PE, using NIH Toolbox Composite Score changes from baseline to post-treatment with a 2-tailed t-test. Exploratory analyses will assess compare responders vs. non-responders on the composite score and the 7 tasks comprising the NIH-TB to assess whether there may be particular aspects of cognitive function that may be more likely to respond to one form of treatment as opposed to the other. Due to COVID-19 the full study can now be conducted by video conferencing, though without the NIH-TB or blood draw.

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