Clinical Research Directory

Advancing Couple and Family Alcohol Treatment Through Patient-Oriented Research and Mentorship

Intimate partner violence (IPV) is a serious public health problem that results in significant health and economic burdens including mortality, morbidity, and poor treatment outcomes. A well-developed field of research suggests that alcohol misuse and posttraumatic stress disorder (PTSD) can lead to IPV. Individuals with PTSD and/or problematic drinking behaviors are at risk for IPV because of several factors that are common symptoms of PTSD. Because individuals with PTSD often drink alcohol to "self-medicate" or cope with distressing PTSD symptoms, PTSD co-occurs with alcohol misuse and alcohol use disorder at extraordinarily high rates. However, few studies have examined the combined effects of alcohol misuse and PTSD on any form of violence. This study will examine the effects of alcohol misuse and posttraumatic stress disorder (PTSD) on alcohol-related intimate partner violence (IPV). We will examine these associations among couples (N=70) in a controlled laboratory setting using validated, standardized methods in a 'real-world' settings using 28 days of ecological momentary assessment (EMA).

tAN for PTSD and OUD in Buprenorphine Therapy

The goal of this research study supported by the HEAL Initiative (https://heal.nih.gov) is to investigate the effects transcutaneous auricular neurostimulation (tAN), as delivered through the Sparrow Ascent device, on helping people with co-occurring posttraumatic stress disorder (PTSD) and opioid use disorder (OUD) start and continue buprenorphine treatment. The main questions it aims to answer are: * Does the tAN help participants with OUD and PTSD remain in buprenorphine therapy for three months after starting use of the device (i.e., randomization to treatment condition)? * Do participants find the Sparrow Ascent device to be acceptable and use it? * Do participants find the Sparrow Ascent device to be tolerable and comfortable to use? * Do participants find the Sparrow Ascent device to be easy to use with their buprenorphine therapy? * Do participants follow the minimum recommended dose schedule for the Sparrow Ascent device most of the time? Participants will complete a baseline assessment to make sure that they are eligible to participate in the study. The assessment captures information about demographics, substance use and treatment history, opioid withdrawal symptoms and craving, difficult life experiences and PTSD symptoms, mental health and treatment history, quality of life, and recovery resources. After the assessment is complete and the participant has been inducted on buprenorphine as part of standard care, they are randomized to one of two treatment conditions: active tAN and placebo. Participants are trained on how to use the device and return for 12 weekly research visits to check on recent substance use and craving, PTSD symptoms, and their experience using the device. After 12 weeks of using the device, participants will complete a post-active treatment assessment that is nearly identical to the baseline assessment to see if there have been changes in these areas. Researchers will access the medical record to determine whether there is a current prescription for buprenorphine at three months and six months after randomization.

Repurposing Low-Dose Clonidine for PTSD in Veterans

Hypothesis: Veterans with PTSD prescribed clonidine will demonstrate improvements in PTSD symptoms, including daytime, nighttime, and sleep-related behaviors.

Biomolecular Characteristics of Reminder-Focused Positive-Psychiatry

Objective: Posttraumatic stress disorder (PTSD) is a prevalent neuropsychiatric disorder in children and is associated with increased neurovascular inflammation, suicidality, adulthood mental health disorder, and major adverse events. Reminder focused positive psychiatry (RFPP) has been shown as well tolerated feasible trauma focused intervention that is associated with improved core PTSD symptoms, decreased severity of reactivity to PTSD trauma reminders, and increased vascular function. This study evaluates the clinical and biomolecular characteristics of RFPP in adolescents with PTSD. Research Design/Overall Impact: After obtaining parents' informed consent and adolescent's assent, 60 adolescents aged 11-15 years old with PTSD, and free of known medical and other major psychiatric disorders will be recruited from the pool of eligible adolescents at Olive View UCLA Pediatrics Clinics (\>3000 adolescents with PTSD). Eligible adolescents will be randomized to 1) RFPP group intervention, or 2) an attentional control condition (group process). Thirty subjects in each group will receive twice weekly telehealth intervention of either RFPP or group process, for 6 weeks, and undergo 4 blinded neuropsychiatric assessments at baseline, 3, 6, and 24 weeks. Parents will receive weekly interventions of either positive psychoeducation or group process, for 6 weeks and undergo baseline, 3, 6- and 24-weeks neuropsychiatric assessment. Vascular function, inflammatory biomarkers including CRP, homocysteine, and stress involved gene expression biomarkers (i.e. changes in gene expression of FKBP5, DDX6, B2M, LAIR1, RTN4, NUB1, and a multi-gene Conserved Transcriptional Response to Adversity score (CTRA) will be measured at baseline and 6-week. The primary and secondary endpoints are a) changes in PTSD core and reactivity to trauma reminder severity score in response to RFPP intervention, b) changes in wellbeing, biopsychosocial trait, vascular function, neuroinflammation and gene expression biomarkers in response to RFPP, and c) changes in parents' wellbeing and biopsychosocial trait as well as child-parent interactions.

Transdiagnostic Versus Diagnosis-specific Cognitive-behavioral Therapy

The primary aim of the pilot study is to investigate the feasibility of conducting a randomized controlled trial (RCT) comparing the effects of transdiagnostic and diagnosis-specific cognitive-behavioral therapy (CBT) for patients with anxiety disorders in routine psychiatric outpatient care in Stockholm, Sweden. It is hypothesized that an RCT is feasible in terms of recruitment, retention, therapist competence and adherence to treatments, and that the treatments are well received by participants.

Family Involvement in Treatment for PTSD (FIT-PTSD): A Brief, Feasible Method for Enhancing Outcomes, Retention, and Engagement

Although effective treatments for PTSD exist, high rates of treatment dropout and sub-optimal response rates remain common. Incorporating family members in treatment represents one avenue for improving outcomes and providing Veteran-centered care, and surveys of Veterans in outpatient VA PTSD care indicate that 80% desire family involvement. The VA has invested many years and millions of dollars on the dissemination of Cognitive Processing Therapy (CPT) and Prolonged Exposure (PE) for PTSD. A family-based intervention that complements these two first-line treatments would capitalize on existing treatment infrastructure while also potentially boosting outcomes and retention. Preliminary testing of the proposed Brief Family Intervention (BFI) resulted in 50% less dropout from CPT/PE among Veterans whose family members received the BFI. There was also a large impact on PTSD symptoms at 16 weeks (d = 1.12) in favor of the BFI group. The goal of this study is to test the effectiveness of the BFI among a fully-powered sample. One hundred Veteran-family member dyads (n = 200) will be recruited. Veterans will be beginning a course of usual-care CPT or PE at one of two VA sites. Family members will be randomized to receive or not receive the BFI, a two-session psychoeducational and skills-based protocol. PTSD symptom severity and treatment retention will be the primary outcomes. Assessments will be conducted by independent evaluators at baseline, 6-, 12-, 18-, and 26-weeks. Veterans whose family members receive the BFI are expected to have lower dropout and a greater rate of change in their PTSD symptoms compared to Veterans whose family members do not receive the BFI. If the BFI is found to increase the effectiveness of and retention in CPT/PE, it will be a highly appealing option for incorporating families into Veterans' PTSD care.

Exploring Efficacy of Multi-Mode Cognitive Processing Therapy (CPT) for PTSD

This study is a longitudinal, multicenter, single-blind, two-arm randomized controlled trial designed to evaluate the effectiveness of Multi-Modal Cognitive Processing Therapy (MMCPT) for individuals with posttraumatic stress disorder (PTSD). Participants will be randomly assigned to either the intervention group receiving MMCPT or a control group receiving treatment-as-usual (TAU). The intervention follows the standard CPT manual developed by Resick and consists of twelve weekly 90-minute individual sessions. The primary outcomes include PTSD symptom severity assessed by the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) and the PTSD Checklist for DSM-5 (PCL-5). Secondary outcomes include sleep quality (actigraphy, PSQI), anxiety (STAI), depression (HDRS-17), remission rate, and posttraumatic growth (PTGI). Assessments will occur at baseline, mid-treatment, post-treatment, and at 3-, 6-, 9-, and 12-month follow-ups.

A Randomized Controlled Trial of a Web-Based Moral Elevation Intervention for Veterans With PTSD

Despite the availability of evidence-based treatments for PTSD, there are many challenges to successful trauma recovery for Veterans including difficulties starting and completing these treatments and gaps in fully addressing additional important treatment targets including lower social functioning and quality of life. Alternative, stand-alone treatment options that address a range of outcomes and can be easily accessed are needed to expand the reach of PTSD treatment to Veterans. One way to address this need is with a positive psychology intervention called MOVED, which has shown promise in a prior pilot study. MOVED is a web-based, self-guided intervention (8 sessions, 4 weeks) that uses moral elevation-feeling inspired by others' virtuous actions. This clinical trial will test if MOVED leads to decreased PTSD symptoms and increased social functioning and quality of life compared to a generic supportive treatment that does not focus on moral elevation. Results will help determine if MOVED is a useful alternative approach to target trauma recovery among Veterans with PTSD.

Ketamine, SGB and Combination Treatment for TBI

Post-Traumatic Stress Disorder (PTSD) and traumatic brain injury (TBI) with associated headache are amongst the most common injuries sustained by our deployed forces in Iraq and Afghanistan, as well as in more recent conflicts in Eastern Europe and the Middle East. This study aims to determine whether a procedural intervention (stellate ganglion block (SGB)) or medication (ketamine), alone or in combination, can alleviate PTSD and TBI-associated headache. Determining efficacious treatments in a randomized, double-blind, placebo-controlled, multicenter study trial may improve quality of life in those with TBI and PTSD, and identifying factors associated with treatment outcome (personalized medicine) may enhance selection, thereby improving the risk: benefit and cost-effectiveness ratios. Primary Objectives: 1. To determine the efficacy of SGB and ketamine infusion as stand-alone treatments for TBI-related headache; 2. To determine the efficacy of SGB and ketamine infusion as stand-alone treatments for PTSD; 3. To determine the comparative effectiveness of SGB and ketamine infusion, and the effect of combination treatment on TBI-related headache and PTSD; 4. Exploratory Aim 1: To determine the effects of SGB, ketamine infusion, and the combination on structural and functional MRI, biomarker levels and pain thresholds and tolerance; 5. Exploratory Aim 2: To identify factors associated with treatment responders overall and for individual treatment groups. Secondary Objectives: 1. Exploratory Aim 1: To determine the effects of SGB, ketamine infusion, and the combination on structural and functional MRI, biomarker levels and pain thresholds and tolerance (Biomedical levels and MRI not included at Northwestern University Site). 2. Exploratory Aim 2: To identify factors associated with treatment responders overall and for individual treatment groups.

Adaption of the STAIR-NT Trauma Intervention for Polysubstance Populations

During this 36-month R34 trial, eight study phases are proposed to adapt an evidence-based post traumatic stress disorder (PTSD) intervention (STAIR-NT) and layer it into a methadone maintenance treatment (MMT) program (START Treatment and Recovery centers) in New York City for use among individuals engaged in stimulant-opioid polysubstance use. The study aims to adapt STAIR-NT to a massed treatment schedule. Once an adapted protocol is complete, it will be tested for feasibility, acceptability, and short-term polysubstance and PTSD symptomology outcomes in a pilot randomized control trial (RCT) of 80 participants. Participants who screen eligible and consent will be randomized 1:1 to the adapted STAIR-NT intervention or treatment as usual (TAU) using randomization blocks of two and two and four via a computer-generated randomization sequence. Participants assigned to the intervention will receive the adapted massed delivery of STAIR-NT by trained counselors.

CIH Stepped Care for Co-occurring Chronic Pain and PTSD

The goal of this clinical trial is to evaluate the feasibility, acceptability, appropriateness, and retention of patient participants of a CIH Stepped Care approach for co-occurring chronic pain and PTSD vs. treatment as usual in two primary care settings (one rural and one urban). Researchers will compare CIH Stepped Care to treatment as usual. Participants will complete assessments at baseline, 3-months, 6-months, and 9-months, and those in the CIH Stepped Care condition will participate in the intervention while also completed assessments every 2-weeks, which helps determine their treatment. We hypothesize that, at 6-months, CIH Stepped Care will be feasible, acceptable, and appropriate (defined by an average of 4/5 on each measure) to patients and clinic employees and result in at least 70% of individuals be retained in each condition (n=21 per condition).

Self-Help Cognitive Processing Therapy (CPT)/Women Veterans Network (WoVeN) Study

Posttraumatic stress disorder (PTSD) can have significant impairment on aspects of mental well-being (MWB) including functioning, loneliness, physical health, and quality of life. There are several evidence-based treatments (EBPs) effective in treating PTSD such as Cognitive Processing Therapy (CPT) which is a specific type of cognitive behavioral therapy that has been proven effective in reducing symptoms of PTSD. However, there are several barriers (e.g., lack of providers, waitlists, costs, stigma, disabilities that complicate travel) that can prevent someone from engaging with these treatments. Recently, a self-help version of CPT was created to help address these barriers; but little research has been conducted to test its efficacy. Further, less is know about how a peer support program may augment improvements from participating in an EBP. The Women Veteran Network (WoVeN), a peer support program designed for women veterans, has a manualized 8-week program that directly targets MWB. It has been found to help foster belongingness and connectedness, particularly in those suffering from PTSD and depression. The present study aims to establish the feasibility, acceptability and tolerability of a scalable, sustainable, and effective treatment option for trauma survivors with subthreshold or full PTSD. The overarching goal is to understand the effectiveness of a self-help version of an EBP (either alone or in combination with a peer support program) in reducing PTSD symptoms while also helping improve mental well-being, reduce barriers, and increase access to quality care within health disparity populations.

Written Exposure Therapy for Veterans With SUD and PTSD

The proposed project will evaluate the efficacy of written exposure therapy (WET) among Veterans engaged in substance use disorder (SUD) treatment, who present with co-occurring posttraumatic stress disorder (PTSD). While SUD treatment programs traditionally do not address PTSD, effective trauma treatments have been used successfully among those with substance use comorbidities. WET is a brief trauma-focused intervention shown to effectively treat PTSD. In a recent acceptability and feasibility pilot study among Veterans with co-occurring SUD and PTSD, results showed a decrease in PTSD symptoms among participants receiving WET. The goal of the present study is to improve outcomes for Veterans who present for SUD treatment with comorbid SUD/PTSD.

Predicting Responses to PTSD Treatment With Iris and Cardiovascular Tests

Posttraumatic stress disorder (PTSD) affects many individuals who experience a traumatic event. There are a variety of treatment options for PTSD, including psychotherapy (talk therapy) options, as well as medications, such as the drug prazosin. Each of the treatment options available is effective at significantly reducing the symptoms of PTSD in some, but not all, individuals with PTSD. However, investigators are not yet able to predict in advance who is likely to respond to which of the available treatments. Neither are the investigators able to explain what changes in the brain after exposure to a traumatic stressors, and why it results in persistent symptoms of PTSD for some people, but not for others. In this study, the investigators are testing two things: First, is testing whether two simple, easy tests of how an individual's blood pressure changes with standing and how an individual's eye reacts to a pulse of light may be able to predict whether that person is likely to respond to the medication prazosin for PTSD. Second, is testing whether those who have been exposed to a traumatic stress show differences in how their body regulates the response to the stress-signal noradrenaline.

Trauma BPE Prolonged Exposure Therapy for Injured Individuals Admitted to a Level I Trauma Center

The purpose of this research is to determine if a brief treatment method is effective for preventing posttraumatic stress disorder (PTSD) and a number of other concerns following injury.

Increasing Treatment Access in Trauma Exposed Children: Developing an Adapted Step One Intervention (Pilot)

One of the most common and widely disseminated trauma treatments is Trauma Focused Cognitive Behavioral Therapy (TF-CBT). TF-CBT is a therapist-led, structured and sequential intervention, with treatment organized around P.R.A.C.T.I.C.E. (Psychoeducation, Parent training, Relaxation, Affective Regulation, Cognitive Coping, Trauma Narrative, In-Vivo Exposure, Cognitive Reprocessing, and Enhancing Safety) components. Stepped Care Cognitive Behavioral Therapy for Children after Trauma (SC-CBT-CT) is an alternative delivery system that incorporates the best available evidence on the treatment of childhood Post-traumatic Stress Disorder (PTSD) within a stepped care model and utilizes task-shifting with caregiver involvement, which engages caregivers in actively helping their children. Stepped care approaches are characterized by a personalized approach to care in which a lower intensity (i.e., fewer number of sessions) intervention is initially provided before the child is reevaluated or ''stepped up'' for additional care should symptoms persist. The goal of this study is to assess a personalized modification of SC-CBT-CT for Latino families (pSC-CBT-CT). The hypothesis is that personalizing SC-CBT-CT will improve outcomes for Latino children.

Increasing Treatment Access in Trauma Exposed Children: Developing an Adapted Step One Intervention (RCT)

One of the most common and widely disseminated trauma treatments is Trauma Focused Cognitive Behavioral Therapy (TF-CBT). TF-CBT is a therapist-led, structured and sequential intervention, with treatment organized around P.R.A.C.T.I.C.E. (Psychoeducation, Parent training, Relaxation, Affective Regulation, Cognitive Coping, Trauma Narrative, In-Vivo Exposure, Cognitive Reprocessing, and Enhancing Safety) components. Stepped Care Cognitive Behavioral Therapy for Children after Trauma (SC-CBT-CT) is an alternative delivery system that incorporates the best available evidence on the treatment of childhood Post-traumatic Stress Disorder (PTSD) within a stepped care model and utilizes task-shifting with caregiver involvement, which engages caregivers in actively helping their children. Stepped care approaches are characterized by a personalized approach to care in which a lower intensity (i.e., fewer number of sessions) intervention is initially provided before the child is reevaluated or ''stepped up'' for additional care should symptoms persist. The goal of this study is to assess a personalized modification of SC-CBT-CT for Latino families (pSC-CBT-CT). The hypothesis is that personalizing SC-CBT-CT will improve outcomes for Latino children.

Enhancing Psychotherapy for Veterans and Service Members With PTSD and Anxiety

The goal of this clinical trial is to compare two different intensive formats of delivering cognitive-behavioral treatment for people with PTSD and anxiety disorders. The main questions it aims to answer are: * Is iTCBT delivered in individual and group formats more effective than TAU in improving anxiety symptoms and quality of life? * For treatment non-responders, is iTCBT-Enhanced more effective than TAU improving anxiety symptoms and quality of life? * Does iTCBT-Individual produce a larger improvement in anxiety and quality of life compared with iTCBT-Group? Participants will undergo several assessments throughout the course of the study. Based on randomization, they will receive: (1) iTCBT in an individual format over a 2-week period, (2) iTCBT in a group format over a 2-day period, or (3) usual care. Those who do not show a response to treatment will receive 4 additional individual therapy sessions.

Focused Ultrasound for PTSD in Veterans

The goal of this study is to develop a new, non-invasive brain stimulation modality called low intensity focused ultrasound (FUS) as a psychiatric rehabilitation treatment for posttraumatic stress disorder (PTSD). FUS delivers energy comparable to that involved in diagnostic ultrasound but in a millimeter-sized envelope. Unlike currently available methods, the maximal FUS energy is delivered at a distance from a transducer on the scalp. Therefore, its promise is that it can deliver focal and reversible modulation to deeper brain regions involved in PTSD. The investigator team has previously conducted first-in-human research in FUS, and this study builds upon that work to conduct a phase II, dose-finding study. This study will pursue two Aims; the first is whether FUS to the amygdala can improve symptoms, and the second will evaluate whether FUS improves function by reduced disability, over a 1-month period. Short and longer-term effects of FUS will be measured and all FUS parameters are within FDA-defined safety thresholds for diagnostic ultrasound.

Mitigating PTSD-CUD After Sexual Assault

683,000 women are sexually assaulted annually in the United States, half of whom develop chronic posttraumatic stress disorder (PTSD) and thus have markedly increased risk for cannabis use disorder (CUD). The current proposal will test the acceptability, initial efficacy, and mechanisms underlying a novel digital therapeutic targeting risk for PTSD-CUD, which could address the critical need for PTSD-CUD prevention for the 100,000 women who annually present for emergency care after sexual assault. In this research context, the applicant will receive key training in multisite, emergency-care based randomized clinical trials (RCTs), advanced statistical analyses for RCTs and ecological momentary assessment data, biobehavioral mechanisms underlying PTSD-CUD prevention, and professional development, launching her independent research career focused on reducing the public health burden of PTSD-CUD among sexual assault survivors by leveraging digital therapeutics.

Evaluation of the PE Coach Mobile Application Among Veterans With PTSD

Thousands of mental health mobile applications (apps) are available but limited research has been conducted on their effectiveness. VA has been a leader in mental health mobile app development and must research whether these apps work, and if so, how? PE Coach is a well-designed treatment companion app to one of the most researched, efficacious psychotherapies for PTSD (prolonged exposure), a treatment that has been broadly disseminated throughout VA mental health clinics. Research suggests that VA therapists find the app helpful in supporting patients. Preliminary results suggest that Veteran patients prefer to receive therapy with PE Coach and Veterans complete more recovery-oriented homework when they do. This study will randomize 124 Veterans with PTSD to treatment with or without PE Coach. The project will evaluate the effect of the app on PTSD-related functioning, quality of life, and PTSD symptoms. The investigators will test whether the app improves functioning and symptoms, increases homework, and reduces drop out.

Art Therapy and Emotional Well Being in Military Populations With Posttraumatic Stress Symptoms

Art therapy is used across the Military Health System for treatment of posttraumatic symptoms, but there is limited research on how art therapy is able to restore emotional expression and regulation in service members. This research hopes to learn about the effects of art therapy on emotional expression and regulation in service members as well as the neurological systems at work. If a participant chooses to be in this study, he or she will attend eleven sessions over a period of six to eight months. The first session will be an interview and self-assessment questionnaires to collect information on a variety of symptoms, experiences, and personality traits, and an MRI scan. During the MRI scan, participants will be asked to perform a task where they will be shown a series of neutral and negative images. The following eight sessions will be one-hour art therapy sessions with a certified art therapist. The tenth session will consist of the same self-assessment questionnaires and another MRI scan. The final session will consist of some of the same questionnaires from the tenth visit, as well as a qualitative interview done virtually three months after the tenth visit.

A Comparison of Prolonged Exposure Therapy, Pharmacotherapy, and Their Combination for PTSD

Posttraumatic Stress Disorder (PTSD) remains a salient and debilitating problem, in the general population and for military veterans in particular. Several psychological and pharmacological treatments for PTSD have evidence to support their efficacy. However, the lack of comparative effectiveness data for PTSD treatments remains a major gap in the literature, which limits conclusions that can be drawn about which of these treatments work best. The current study will compare the effectiveness of PTSD treatments with the strongest evidentiary support - Prolonged Exposure (PE) therapy and pharmacotherapy with paroxetine or venlafaxine - as well as the combination of these two treatments. A randomized trial will be conducted with a large, diverse sample of veterans with PTSD (N = 300) recruited from 6 VA Medical Centers throughout the US. Participants will complete baseline assessments, followed by an active treatment phase (involving up to 14 sessions of PE and/or medication management) with mid (7 week) and posttreatment (14 week) assessments, and follow-up assessments at 27 and 40 weeks. Study outcomes will include PTSD severity, depression, quality of life and functioning, assessed via clinical ratings and self-report measures. Further, a range of demographic and clinically relevant variables (e.g., trauma type/number, resilience) will be collected at baseline and examined as potential predictors or moderators of treatment response, addressing another gap in the PTSD treatment literature. These data will be used to develop algorithms from predicting the optimal treatment for individual patients (i.e., "personalized advantage indices"; PAIs). Effectiveness of the treatments will be compared using multilevel modeling. PAIs will be developed by conducting bootstrapped analyses to select variables that predict or moderate outcomes (clinician rated PTSD severity at Week 14), followed by jacknife analyses to determine the magnitude of the predicted difference (representing an individual's "predicted advantage" of one treatment over the others).

Adaptive Decision-making And Personalized Treatment for PTSD (ADAPT-PTSD)

By doing this research project, the investigators hope to learn which strategies work best to help veterans who are not benefiting from their first PTSD treatment or not completing between-session homework assignments regularly that might improve treatment response. The investigators also want to learn how best to match the right type and amount of treatment to each individual veteran. By conducting this research project, they hope to: * See if trying a different treatment strategy for veterans not responding to their first PTSD treatment would be more helpful * See if sending text message prompts between sessions encourages more completion of between-session homework