Clinical Research Directory

Multi-site, Longitudinal Trial Evaluating the Efficacy, Mechanisms, and Moderators of Service Dogs for Military Veterans With PTSD

Posttraumatic stress disorder (PTSD) among military Veterans is a critical public health concern. Veteran suicide rates exceed those of the general population, with the disorder creating a mental health challenge that is costly and debilitating. The majority of Veterans with PTSD also have comorbid mental health diagnoses, such as generalized anxiety disorder, substance abuse disorder, and major depression. The treatment of Veteran PTSD and comorbid disorders represents an important therapeutic and rehabilitation problem. The disorder is complex and difficult to treat, with high treatment dropout and nonresponse rates spurring some Veterans to seek complementary integrative health strategies. One promising complementary strategy is the provision of a trained service dog. Initial evidence across multiple research groups highlights service dogs as a promising complement to evidence-based practices that can offer short-term improvements. However, the long-term effectiveness, mechanisms of action, and moderators of efficacy remain largely unknown. Thus, the overarching objective of this proposal is to understand how, why, and for whom PTSD service dogs are most effective. To address this objective, the present project will assess the longitudinal efficacy and dose-response curve of service dogs for Veteran PTSD symptomology and psychosocial functioning. The research design will consist of a two-arm, randomized clinical trial (RCT) with longitudinal assessments over a period of 15 months. Results are expected to elucidate the clinical impact of service dogs for military Veterans with PTSD, as well as the biobehavioral mechanisms of action and characteristics that moderate efficacy. These outcomes will support the long-term goal of accelerating complementary and integrative health interventions, through optimized and evidence-based service dog interventions. As such, this project will further advance the scientific understanding of human-animal interactions for psychosocial health.

Self-Help Intervention for Post 9/11 Veterans With Depression or PTSD Symptoms

It is important to provide support and resources for the many post-9/11 Veterans with mental health symptoms and poor psychosocial functioning who do not engage in psychotherapy. One of the biggest reasons post-9/11 Veterans do not seek treatment is a preference to handle problems on their own. This study examines a self-help intervention that teaches Veterans healthy coping strategies they can use on their own and how to seek out recovery support services such as mental health treatment or whole-person care if they decide to do so in the future. This study will compare the impact of self-help and standard resources at improving mental health and resource utilization. Two hundred Veterans will complete 6 brief assessments across 40 weeks.

Massed Prolonged Exposure for PTSD in Substance Use Treatment

The goal of this clinical trial is to learn if receiving Prolonged Exposure Therapy for PTSD in massed format (multiple sessions weekly) is as effective as receiving it with sessions once per week among veterans with PTSD and substance use disorder in intensive outpatient substance use treatment. The main questions it aims to answer are: * Will the massed format help participants complete and benefit from Prolonged Exposure in terms of PTSD symptoms? * Will it help participants reduce substance use? Participants who are in intensive substance use treatment will be asked to complete Prolonged Exposure with either weekly sessions or multiple sessions per week.

Trauma-Informed Guilt Reduction Therapy Compared to Prolonged Exposure

The goal of this clinical trial is to learn if receiving Trauma-Informed Guilt Reduction (TrIGR) Therapy is as effective as receiving Prolonged Exposure Therapy among veterans with PTSD and trauma related guilt. The main questions it aims to answer are: Will TrIGR be comparable to PE in terms of PTSD symptom reduction? Will it TrIGR be comparable to PE in improving functioning and reducing depression symptoms? Will it be superior in improving trauma-related guilt and shame?

SMART Therapist Training: A Hybrid Factorial-SMART Design

Cognitive Processing Therapy (CPT) is highly effective in randomized controlled trials, but its effectiveness drops substantially in standard clinical practice, largely due to therapist "drift" from fidelity to the protocol. What remains unknown is which components of CPT training yield high therapist fidelity. Thus, there is a critical need to use empirical approaches to identify the most effective components of CPT training and to develop an adaptive training model for CPT by testing sequences of empirically-supported training strategies. The long-term goal of this research is to develop a sustainable model of therapy training that is personalized to the needs of the therapist trainee. The overall objective of this application is to empirically optimize an adaptive model for CPT training. The rationale is that developing an adaptive training model will improve efficiency and personalization, yield higher fidelity, and ultimately improve Veteran outcomes. The investigators expect that completion of this project will produce an adaptive CPT training program that yields high therapist fidelity. Improving CPT fidelity in VHA will have a positive impact on the health and wellbeing of Veterans with PTSD.

Enhancing Memory in Cognitive Processing Therapy for PTSD

Several psychotherapies for posttraumatic stress disorder (PTSD) have a strong evidence base for their efficacy, but nonresponse rates are high, particularly among older Veterans. Accumulating evidence indicates that memory deficits and poor learning of therapy contents adversely affect psychotherapy treatment response in PTSD. However, limited research has examined methods for increasing learning of therapy contents in psychotherapy for PTSD. The proposed study aims to examine the feasibility of integrating an intervention to increase learning and memory of psychotherapy content into the provision of a widely used psychotherapy, cognitive processing therapy (CPT), for older adults with PTSD. The ultimate goal of this line of research is to develop novel rehabilitation interventions to increase functioning for individuals with PTSD.

Pre-Pilot (R61) WINGS+++: mHealth to Improve MOUD Uptake in Women Experiencing Intimate Partner Violence and PTSD

The goal of this pre-pilot for the clinical trial is to develop a mobile health (mHealth) program called WINGS+++ can help women with opioid use disorder or other substance use disorders who have experienced intimate partner violence. The pre-pilot study will take place in Orange County, New York with n=7 women. . The main questions it aims to answer are: 1. Does WINGS+++ lower non-prescription opioid and other drug use in women? 2. Does WINGS+++ help connect women to treatment for substance use, intimate partner violence, and post-traumatic stress disorder (PTSD)? Researchers will compare WINGS+++ to standard care to see if WINGS+++ works better to lower drug use and link women to helpful services. WINGS+++ is a 3-session program on a mobile device that: * Screens for intimate partner violence, PTSD, and substance use * Offers brief support and referrals based on each woman's needs and preferences * Connects women to a peer navigator who helps link them to services Participants will: * Take part in only the WINGS+++ program for the pre-pilot * Answer survey questions about drug use, intimate partner violence, and PTSD symptoms * Provide biological samples (such as urine or hair) to check for drug use * Share information about the services they have used

Mantram Repetition Versus Health Education for Veterans With PTSD and Chronic Pain

Approximately 450,000 Veterans Health Administration service users have both posttraumatic stress disorder (PTSD) and chronic pain (CP); treatments that efficiently target both PTSD and CP are limited, and new interventions should address the unique needs of Veterans with PTSD/CP. Mantram Repetition Program (MRP), a meditation-based program, appears well-suited to address these high-priority VA needs. MRP has established effectiveness for treatment of PTSD, is broadly acceptable, can be learned quickly and applied flexibly. However, rigorous testing is needed for pain-related outcomes among a PTSD/CP population. The proposed study will include a randomized controlled trial comparing the efficacy of MRP for PTSD/CP to Health Education while Living with Pain among a sample of 170 Veterans with comorbid PTSD/CP. The primary outcomes will be PTSD symptoms and pain interference. Results from this study will directly inform patient care among the nearly 4% of Veterans with PTSD/CP.

Intervention to Enhance Coping and Help-seeking Among Youth in Foster Care

This study will deploy a scalable secondary prevention program that leverages existing foster youth transition services to improve mental health functioning and service use before and after exiting foster care. Our short-term objective is to remotely test a group intervention called Stronger Youth Networks and Coping (SYNC) that targets cognitive schemas influencing stress responses, including mental health help-seeking and service engagement, among foster youth with behavioral health risk. SYNC aims to increase youth capacity to appraise stress and regulate emotional responses, to flexibly select adaptive coping strategies, and to promote informal and formal help-seeking as an effective coping strategy. The proposed aims will establish whether the 10-module program engages the targeted proximal mechanisms with a signal of efficacy on clinically-relevant outcomes, and whether a fully-powered randomized control trial (RCT) of SYNC is feasible in the intended service context. Our first aim is to refine our SYNC curriculum and training materials, prior to testing SYNC in a remote single-arm trial with two cohorts of 8-10 Oregon foster youth aged 16-20 (N=26). Our second aim is to conduct a remote two-arm individually-randomized group treatment trial with Oregon foster youth aged 16-20 with indicated behavioral health risk (N=80) to examine: (a) intervention group change on proximal mechanisms of coping self-efficacy and help-seeking attitudes, compared to services-as-usual at post-intervention and 6-month follow-up: and (b) association between the mechanisms and targeted outcomes, including emotional regulation, coping behaviors, mental health service use, and symptoms of depression, anxiety, and PTSD. Our third aim is to refine and standardize the intervention and research protocol for an effectiveness trial, including confirming transferability with national stakeholders.

Overcontrol and Suicide in PTSD

High standards and self-discipline are prized in military culture, but drawbacks of overcontrol are often ignored. Overcontrol is characterized by over-regulated behavior and cognitive rigidity, driven by an intense need for perfection and control. It is frequently observed in people with obsessive-compulsive (OC) spectrum disorders, especially OC Personality Disorder (OCPD). Their inclination to set high expectations for others can strain social bonds. When grappling with mental health challenges, overcontrolled individuals often do so with limited social support, and as a result, tend to be at greater risk of developing more severe mental health symptoms, or suicidal thoughts and behaviors, over time. New treatments are needed to improve social functioning in these vulnerable Veterans. Adding brain stimulation to psychotherapy is one method that might speed learning of social skills discussed in therapy. However, before this technology can be developed and tested more broadly, the investigators must make sure that the methods used to measure social functioning and related brain circuits are acceptable to most potential patients and can be used consistently. In this pilot project, the investigators aim to recruit trauma-exposed Veterans with overcontrolled traits and study the feasibility and acceptability of: 1. Our recruitment strategy and social functioning and mental health symptom assessments 2. A three-session, weekly fMRI protocol. 3. A three-week online protocol for remote monitoring of social and emotional functioning.

CPT-SMART for Treatment of PTSD and Cigarette Smoking

Smoking is the leading cause of preventable illness, disability, and death in the United States. The rate of smoking is disproportionately higher among Veterans with posttraumatic stress disorder (PTSD). Unfortunately, smoking cessation efforts that are effective in the general population have shown limited effectiveness in smokers with PTSD. The high smoking rate and difficulty with achieving abstinence indicate a critical need to develop effective interventions for Veterans who smoke and have PTSD. The investigators' data indicate that negative emotions and trauma reminders are associated with relapse for smokers with PTSD. In this context, an ideal strategy may be to combine evidence-based PTSD treatment with intensive smoking cessation treatment to maximize quit rates. Cognitive processing therapy (CPT) is a well-established evidence-based treatment for PTSD. The investigators have successfully developed a treatment manual that combines CPT with cognitive-behavioral counseling for smoking cessation. Contingency management (CM) is another intensive behavioral treatment that has been shown to help with reducing smoking. CM provides positive reinforcers such as money to individuals misusing substances contingent upon abstinence from use. The primary goal of this study is to evaluate the efficacy of a treatment that combines CM with cognitive-behavioral smoking cessation counseling, smoking cessation medication, and CPT. Proposed is a randomized, two-arm clinical trial in which 120 Veteran smokers with PTSD will be randomized to either: 1) COGNITIVE PROCESSING THERAPY with SMOKING ABSTINENCE REINFORCEMENT THERAPY (CPT-SMART) or 2) COMBINED CONTACT CONTROL, an intervention identical to CPT-SMART in PTSD and smoking treatment, except for using payment that is not contingent on abstinence. Specific aims include: AIM 1) To evaluate the efficacy of CPT-SMART on rates of short- and long-term abstinence from cigarettes; AIM 2) To evaluate the impact of CPT-SMART on treatment engagement and utilization; and an EXPLORATORY AIM) To explore mechanisms of CPT-SMART on long-term smoking abstinence. The positive public health impact of reducing smoking among Veterans with PTSD could be enormous as it would prevent significant smoking-related morbidity and mortality.

Postnatal Debriefing After Adverse Obstetric Events

Adverse or unexpected obstetric events can negatively affect women's psychological well-being and childbirth experience, increasing the risk of postpartum traumatic stress. However, structured postnatal debriefing is not routinely implemented in clinical practice, and evidence regarding its effectiveness remains limited. This study aims to evaluate the effect of a structured postnatal debriefing conducted within the first 24 hours after childbirth in women who have experienced an adverse or unexpected obstetric event. This quasi-experimental pretest-posttest study will include two consecutive groups: a control group receiving usual postpartum care during the pre-implementation phase and an intervention group receiving structured postnatal debriefing during the implementation phase. The primary outcome is childbirth-related trauma at 6 weeks postpartum. Secondary outcomes include birth satisfaction, early post-traumatic stress symptoms, satisfaction with information and emotional support received after childbirth, and clinical maternal and neonatal outcomes. This study will provide evidence on whether structured postnatal debriefing improves psychological outcomes and contributes to more patient-centered obstetric care.

Computational Assessment of GABA Receptor Modulation in PTSD

A substantial majority of Veterans with posttraumatic stress disorder (PTSD) continue to suffer even with the best current medications. Progress in developing more effective medications is hampered by the substantial variability within Veterans with PTSD, meaning the most effective medication likely varies from individual to individual. New scientific tools to help identify distinct subgroups of Veterans with PTSD who are likely to respond to specific medications could help improve treatment in this population. Research has indicated that a specific subgroup of Veterans with PTSD with a high level of anxious arousal may benefit from medications which boost signaling of the neurotransmitter gamma-aminobutyric acid (GABA). This project aims to validate a clinical test to identify these individuals using new computational and neuroimaging methods combined with the medication lorazepam, a positive GABA modulator. The ultimate goal is to use these methods in future clinical trials of new medications to target the best treatments to individual Veterans with PTSD.

Potentiation of Trauma Exposure in Post-traumatic Stress Disorder by Repeated Transcranial Magnetic Stimulation

The aim of this study is to assess the efficacy in PTSD treatment of concomitant voluntary reactivation of personal traumatic memories with neuromodulation of the right dorsolateral prefrontal cortex using 10Hz rTMS, compared to 1Hz rTMS, during 2 weeks.

Using the Multiphase Optimization Strategy to Adapt Cognitive Processing Therapy

Cognitive Processing Therapy (CPT) consists of discrete therapeutic components that are delivered across 12 sessions, but most Veterans never reach session 12, and those who drop out receive only 4 sessions on average. Veterans drop out because of time constraints, logistics, and lack of perceived benefit. Unfortunately, Veterans who drop out prematurely may never receive the most effective components of CPT and continue to experience symptom-related distress and numerous other negative outcomes, including lost productivity, substance use, later-life physical disability, reduced quality of life, and increased risk of suicide. The overall objective of this study is to adapt CPT into a brief, effective format. The rationale is that identifying the most effective intervention components and delivering only those components will make CPT deliverable in a shorter timeframe, thus improving efficiency, reducing drop-out related to poor treatment response, and ensuring that Veterans receive the most beneficial components of treatment, which will significantly improve their quality of life.

A Transdiagnostic Sleep Health Intervention for Veterans With PTSD

Sleep disturbance is a major problem in Veterans with posttraumatic stress disorder (PTSD). This study will test a version of a sleep treatment that's been shown to be effective in the general population, with some changes to tailor it to the needs of Veterans with PTSD and sleep disturbance.

Manage Emotions to Reduce Aggression (MERA)

PTSD is one of the most prevalent mental health conditions affecting Veterans who have served since 9/11. Veterans with posttraumatic stress disorder (PTSD) report difficulty controlling impulsive aggression (IA). An inability to manage one's emotions (emotion dysregulation) is an underlying mechanism of IA. Reducing IA and increasing use of PTSD evidence-based psychotherapies are two critical missions for the Veterans Health Administration. The proposed research supports these missions by comparing a 3- session emotion regulation treatment (Manage Emotions to Reduce Aggression) to a control group in order to determine if MERA can reduce IA and prepare Veterans for PTSD treatment. By enhancing Veterans' abilities to cope with trauma-related emotions and feel equipped to initiate PTSD treatments, this research aims to help Veterans decrease IA and ultimately recover from PTSD.

Whole Health in VA Mental Health: Omnis Salutis

Recent Veterans of the Afghanistan and Iraq conflicts are presenting in VA care with high rates of posttraumatic stress disorder (PTSD), depression, anxiety, and substance use disorders. Difficulties with social relationships and community reintegration are common functional impairments with these disorders. VA is transforming to a Whole Health, patient-centered system of care that will address these issues as part of health care. In a previous study, Omnis Salutis (OS) was developed with Veteran and clinician input. OS is a three-session intervention in which Veterans learn about Whole Health and practice communicating their health mission to providers and social supports. OS was shown feasible to deliver, acceptable to Veterans, and preliminarily effective at improving physical, mental, and social functioning. This study will use a large, multisite randomized controlled trial to test the impact of OS on Veterans' social and physical functioning and Veteran engagement in mental health care. Results will support broad delivery of OS throughout the VA.

Mismatch vs. Standard Intervention During Memory Reconsolidation Blockade With Propranolol: Effect on Psychophysiological Reactivity During Traumatic Imagery

The proposed R21 project will attempt to further develop a novel intervention for posttraumatic stress symptoms inspired by the science of memory reconsolidation. Work in normal humans has shown that when a stable, consolidated memory is reactivated (i.e., retrieved) under appropriate conditions, it reverts to an unstable state, a process referred to herein as deconsolidation. In such a state, the memory is susceptible to the action of various "amnestic" agents that may inhibit its reconsolidation, thereby weakening it. The β-adrenergic blocker propranolol (PPNL) possesses such amnestic properties. More recent research has found that in order to initiate deconsolidation, there must be a prediction error, or mismatch, between what is expected and what occurs when the memory is reactivated. Prior placebo-controlled, randomized clinical trials (PBO-RCT) from our laboratory have found that when propranolol is administered concomitant with the reactivation of a psychologically traumatic memory, the memory is weakened, as revealed by subsequent lower physiological (heart rate, skin conductance, facial electromyogram) responding during script-driven mental imagery. Clinical applicability was evaluated in a PBO-RCT, in which PTSD participants receiving propranolol underwent six weekly sessions of 10-20 min of "standard" (STD) traumatic memory reactivation stimulated by reading a narrative. At post-treatment, these participants showed a greater reduction of PTSD symptoms compared to participants who had taken PBO. The goal of the proposed study is to test whether intentionally incorporating innovative mismatch (MM) into traumatic memory reactivation can improve upon physiological responding during script-driven mental imagery. Participants will be randomized to one of 2 treatment arms: STD/PPNL and MM/PPNL. A baseline assessment will measure psychophysiological responsivity to script-driven mental imagery (target measure). PPNL will be administered 90-min prior to each of six weekly 10-20 min. traumatic memory reactivation sessions. In the MM condition, a different, unexpected mismatch (e.g., singing the narrative) will be incorporated into the reactivation. In the STD condition, the participant will read the narrative the same way each time. The focus of the R21 proposal will be to assess whether the MM/PPNL group shows lower subsequent physiological responses than the STD/PPNL group

Resettled Refugee Families for Healing

The goal of this type I hybrid effectiveness-implementation trial is to test a family strengthening (FS) model delivered through multiple family groups (MFG) combined with a virtual peer mentoring program called TeenAge Health Consultants (Virtual TAHC) aimed at addressing emotional and behavioral problems among youth born in the U.S. to parents resettled as refugees. The specific aims of the study are: Aim 1: To systematically adapt an evidence-based family strengthening (FS) model delivered through multiple family groups (MFG) combined with a peer mentoring program (Virtual TAHC) (Goal 1). Aim 2: To assess preliminary short- and long-term impact of the combination intervention (MFG + Virtual TAHC) on behavioral emotional disorders (aggressive behavior, antisocial behaviors, anxiety, depression, and Posttraumatic Stress Disorder \[PTSD\]) related to intergenerational trauma among SGRC in the trial (Goal 2). Aim 3: Utilizing mixed methods and applying the Exploration, Preparation, Implementation, Sustainment (EPIS) framework, examine implementation strategies, facilitators, and barriers of the RRF4H intervention (Goal 3). Participants will receive: 1. Family strengthening intervention delivered through multiple family groups (MFG) where children and one of their biological parents will participate in 16 weekly group sessions to discuss common problems and how to address them. 2. The youth in the intervention will participate in a peer mentorship program called TeenAge Health Consultants (TAHC) consisting of 16 weekly virtual sessions where they interact with other youth to learn about important topics including how to deal with conflict, stay out of trouble, deal with stress, avoid drugs and other topics. Researchers will compare the intervention group to a control group that will receive the usual care to see if the intervention group shows improvement in symptoms compared to the usual care group.

Enhancing the Effectiveness of Cognitive Behavioral Therapy Using Non-invasive Brain Stimulation

The purpose of the proposed study is to examine if a repeated treatment of High Definition Transcranial Direct Current Stimulation (HD-tDCS) can increase the functional connectivity between the left ventrolateral prefrontal cortex and posterior cingulate, which may further enhance the effects of cognitive behavioral therapy with mindfulness classes.

Group-based Stabilization and Skill Training for Patients With Lasting Posttraumatic Reactions in Mental Health Care

This study evaluates the addition of a group based stabilization and skill-training intervention to individual out-patient treatment for long lasting post-traumatic reactions. Half of the participants will receive the combined treatment while the other half will receive individual treatment as usual.

fMRI to Examine the Effect of CBTm to Increase Resiliency for PTSD

A substantial proportion of public safety personnel (PSP) develop service-related posttraumatic stress disorder (PTSD). PTSD is associated with a range of negative outcomes and its exact underlying neurophysiological mechanism is still not well understood. Cognitive behavioral therapy (CBT) is commonly prescribed to treat PTSD, and recent studies suggest that it may be effective in preventing the condition. We have developed a 5-session class focused on teaching introductory CBT skills to prevent and manage psychological distress, and we are currently in the process of launching a clinical trial to demonstrate its effectiveness in preventing PTSD and related conditions in PSP. In the proposed adjunctive study to this trial, we will quantitate the brain connectivity signature that is specific to the PTSD-resilience, and examine whether the classes increase this resilience-related brain mechanism.

MOCHA: Embedded Inpatient Mental Health Care for High-Risk Perinatal Patients

Pregnant and postpartum patients hospitalized for medical complications experience high rates of depression, anxiety, and trauma-related symptoms, yet access to timely psychiatric care during obstetric hospitalization is limited. Project MOCHA integrates early mental health screening, trauma-informed psychotherapy, and structured follow-up into routine inpatient maternity care for individuals at elevated clinical risk. This single-arm implementation study examines the feasibility, acceptability, and fidelity of delivering a Collaborative Mental Health Care Program within a high-risk obstetric inpatient setting. The program includes brief inpatient psychotherapy, symptom monitoring, and post-discharge follow-up over three months. Preliminary changes in depression, anxiety, attention-deficit hyperactivity disorder, and posttraumatic stress symptoms will be assessed to inform future effectiveness trials and broader health system integration.