Clinical Research Directory

Neurosteroids for Treatment of PTSD in Veterans

This study seeks to determine if pregnenolone can improve symptoms of PTSD and other symptoms that commonly occur with PTSD in Iraq/Afghanistan-era Veterans. The total study duration for each participant is 10 weeks. Eligible Veterans with PTSD will receive either pregnenolone or placebo throughout the study duration and will complete mental and physical health assessments at each study visit. Eligible participants will attend 6 in-person study visits and receive several short "check-in" phone calls.

Enhancing Week-long Psychological Treatment for PTSD With Ketamine

The purpose of this study is to test if the combination of ketamine, vs midazolam, with an intensive trauma-focused psychotherapy will be more effective in relieving post-traumatic stress disorder (PTSD). This week-long treatment has the potential to produce a significant therapeutic effect that otherwise would take months to occur. The study will also focus on learning about the neurophysiological changes produced by the proposed clinical trial.

Stress, Adjustment And Growth In Children With Cancer And Their Parents

This proposal examines trauma and growth responses in the childhood cancer experience. It addresses a number of gaps and unanswered questions in the literature, while integrating several distinct but related lines of research. The rationale for this proposal is outlined briefly as follows: 1. Traumatic stress models focused on pathology dominate pediatric psychosocial oncology research despite empiric evidence of low levels of post-traumatic stress in this population. 2. The assumption of 'cancer as a traumatic event' has biased research designs (including lack of control comparisons) to focus on deficits and pathological outcomes. 3. This deficit-oriented approach has stimulated the development of interventions to treat or prevent PTSD, which may be unnecessary or even harmful. 4. Theoretical and empiric evidence suggests that a more common response to traumatic stress is growth and positive change, but posttraumatic growth phenomenon have been understudied in pediatric populations. 5. Cognitive and personality factors are important determinants of PTSD and positive growth outcomes, and some constructs from positive psychology theory may be particularly relevant in children with cancer. 6. Empirically, parents of children with cancer appear to be at higher risk of PTSD/PTSS, although results are not unequivocal, and the same research biases have applied to parental outcomes. This proposal includes assessment of parental PTSS and PTG, both as an outcome and a predictor of child outcomes.

Positive Processes and Transition to Health (PATH)

The R33 will be a randomized controlled trial to replicate changes in the targets (unproductive processing, avoidance, reward deficits) from the R61 phase in a larger sample of 135 participants who have experienced a destabilizing life event involving profound loss or threat, report persistent stressor-related symptoms of PTSD and/or depression, and are elevated on symptoms related to 2 of the 3 therapeutic targets. Additionally, this study will examine Positive Processes and Transition to Health (PATH)'s impact on stressor-related psychopathology in comparison to Progressive Muscle Relaxation (PMR). In the R33 phase, the investigators will examine changes in target mechanisms predicting improvements in PTSD and depressive symptoms, as well as feasibility and acceptability. Patients will receive 6 sessions of PATH or PMR (with 2 boosters, if partial responders). Primary targets will be assessed at pre-treatment, week 3, post-treatment, and at 1- and 3-month follow-up; secondary targets at pre-treatment, weekly during treatment, post-treatment, and at 1- and 3-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 post-traumatic stress disorder (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.

The Efficacy of a Pharmacological Treatment (Reboxetine Plus Ritalin) Versus Dog-Assisted Therapy in PTSD

Posttraumatic stress disorder (PTSD) is a chronic and often treatment-resistant psychiatric condition that emerges following exposure to trauma and is characterized by intrusive thoughts, emotional dysregulation, and cognitive impairments. In Israel, the prevalence of PTSD has increased significantly in the aftermath of the October 7, 2023 terror attacks, emphasizing the urgent need for more effective, accessible, and personalized interventions. Existing treatments, such as trauma-focused CBT and SSRIs, remain only partially effective, with side effects that reduce adherence and limit long-term recovery. The proposed randomized controlled trial will assess and compare two promising treatment modalities: (i) a new pharmacological combination of reboxetine and methylphenidate, designed to enhance noradrenergic and dopaminergic pathways involved in attention and emotional regulation, and (ii) dog-assisted therapy (DAT), a non-pharmacological, group-based intervention shown to reduce PTSD symptoms and improve functioning. One hundred sixty adults with PTSD will be randomized into four groups: pharmacological treatment, placebo, DAT, or occupational therapy. The study will use validated clinical scales (CAPS-5, GAD-7, CAARS, DLQ, WHOQOLBREF) alongside neurophysiological tools (EEG, EDA, ASAT-based EMG). Data will feed into a machine-learning model to identify predictors of treatment response and support the development of personalized, neurobiologically informed approaches.

Predicting Responses to PTSD Treatment With Iris and Cardiovascular Tests

Post-traumatic 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.

Efficacy of Reboxetine and Methylphenidate Treatment on Attentional, Sensory and Emotional Dysregulation in Adults With PTSD

Up-to-date, no studies have examined the attentional, sensory and emotional processing (difficulties) among patients diagnosed with Posttraumatic Stress Disorder (PTSD). In addition, the efficiency of drug treatments that focus on the noradrenergic and dopaminergic, and thus influence attention processing and PTSD symptoms through these pathways, have only briefly been investigated. There is well-established and long-standing evidence for the involvement of dopamine and noradrenaline in attentional function. This previously led to an investigation by the investigator's research lab in which the investigators hypothesized the involvement of an attentional disorder would influence PTSD symptoms in a rat model. Based on these results, the current study aims to characterize attentional deficits in patients with PTSD, as well as the correlation between attention, emotional regulation and sensory processing. The investigators do this partially by conducting a case-control study and through a subsequent double-blind RCT (with only the cases). The patients will be either treated with reboxetine + methylphenidate or placebo.

Investigating Cardiac Health of Adults With Trauma

This project examines the impact of a healthy lifestyle intervention, specifically designed for adults with posttraumatic stress and identified cardiovascular risks.

Multicenter iTBS Neuromodulation for PTSD Treatment

The proposed study aims to evaluate the efficacy of intermittent theta-burst transcranial magnetic stimulation (iTBS) targeting primary motor cortex (M1) as adjunct treatment for PTSD patients. The primary outcome measure includes changes in PTSD symptom severity, with secondary outcome measures focusing on negative moods improvements, quality of life and social/occupation functioning and functional connectivity of the brain.

Couple HOPES and COVID-19

Posttraumatic Stress Disorder (PTSD) will be a severe problem in Canada in the wake of COVID-19, especially for Military Members, Veterans, First Responders, and Healthcare Workers (MVFH). However, gold standard face-to-face PTSD treatments do not meet current MVFH needs, which requires virtual interventions and minimal healthcare resources. Recognizing the need for a virtual, low-resource PTSD intervention for MVFH with PTSD and their loved ones, the investigators developed Couple HOPES (Helping Overcome PTSD and Enhance Satisfaction). Couple HOPES is a secure, online self-help intervention for those with PTSD and their partners (www.couplehopes.com). However, MVFH are now particularly likely to be exposed to traumas related to COVID-19. It is essential to identify if Couple HOPES is safe and helpful for couples involving MVFH with COVID-19-related PTSD specifically. This project will therefore test the efficacy of Couple HOPES compared to a delayed waitlist control in 70 couples wherein one member is a MVFH with COVID-19-related PTSD. The investigators will examine if Couple HOPES is helpful in improving PTSD symptoms and relationship satisfaction for such couples, and if it is more or less helpful to this end for these couples compared to those with other forms of trauma exposure. 70 couples including a MVFH with COVID-19-related PTSD, will be randomly assigned to receive Couple HOPES or to a waitlist. PTSD symptoms and relationship satisfaction will be measured \~weekly during the intervention and one month after it. Related problems (e.g., depression, anxiety, healthcare use) will be measured before, in the middle of, after, and one month after, the intervention.

Reducing Psychological Barriers to PrEP Persistence Among Pregnant and Postpartum Women in Cape Town, South Africa

Pregnant women in South Africa (SA) are at high risk of HIV acquisition. Pre-exposure prophylaxis (PrEP) use during pregnancy is both safe and effective in preventing HIV. However, posttraumatic stress (associated with intimate partner violence and/or other traumas) and depression negatively impact PrEP adherence among women in SA. Addressing posttraumatic stress and depression will likely improve PrEP adherence and persistence (i.e., sustained PrEP adherence over time) during pregnancy and breastfeeding, which are periods of dramatically increased HIV risk. The overarching goal of this proposal is to develop and test the feasibility and acceptability of a cognitive behavioral intervention that targets common underlying factors of posttraumatic stress and depression to improve PrEP adherence and persistence during pregnancy and the postpartum transition. The specific aims of the project are to (1) explore the mechanisms by which posttraumatic stress and depression impact PrEP adherence and persistence during pregnancy via qualitative interviews; (2) develop a brief PrEP adherence and persistence intervention (\~4 sessions) that reduces the negative impact of psychological mechanisms common to posttraumatic stress and depression on PrEP use, and builds behavioral skills to improve self-care; and (3) evaluate the feasibility, acceptability, and signals of preliminary efficacy of the intervention, which will be integrated into antenatal care, in a pilot randomized controlled trial. All data will be collected in the Midwife Obstetrics Unit (MOU) in Gugulethu, a peri-urban settlement and former township community outside of Cape Town, SA.

Cognitive Training for Functioning in PTSD

The proposed study will test a novel, computerized treatment for posttraumatic stress disorder (PTSD) to determine if it helps Veterans functionally recover as measured by reduced cognitive disability and PTSD symptoms. To do so, investigators will evaluate the effects of a cognitive training program that is designed to improve people's ability to manage information in working memory. Investigators will measure self-reported symptoms and disability alongside day-to-day cognition and functioning. The project support the VA Office of Research and Development's mission to improve Veteran participation in their lives and community by determining if this new approach can improve recovery from trauma and exploring for whom the intervention works.

Multimodal Image Analysis and Guidance of Neuromodulation for Trauma-Related Symptoms

MAGNETS is a prospective, randomized, parallel-design, sham-controlled clinical trial of accelerated, functional magnetic resonance imaging (fMRI)-guided intermittent theta burst stimulation (iTBS) to the right dorsolateral prefrontal cortex (dlPFC) for chronic symptoms of posttraumatic stress disorder (PTSD) in a comorbid Veteran population.

A Pilot Participatory Program Evaluation of a Virtual Trauma Support Program for Autistic Adults

The goal of this single-group clinical trial is to learn about the initial efficacy and feasibility of telehealth-delivered Written Exposure Therapy (WET) for autistic adults with traumatic stress symptoms. The main questions the investigators aim to answer are: * Do symptoms of posttraumatic stress disorder (PTSD) and co-occurring mental health concerns decrease after receiving WET? * Do biobehavioral health outcomes, including objective (Fitbit indicators of activity, sleep, and heart rate) and subjectively-reported health variables (e.g., sleep, pain, health-related quality of life), improve after receiving WET? * How do autistic adults experience WET, and how can this program be modified and enhance in the future in collaboration with autistic adults? Participants will complete the following as part of the study, which is completed entirely over telehealth. * Participants will first complete an initial assessment, involving brief measures of cognition and autistic traits, as well as interviews and questionnaires about PTSD, mental health, and physical health. If eligible, participants will proceed to the following steps: * Eligible participants will then start wearing a Fitbit, to be used for the duration of the study. * Participants will then participate in 5 weekly virtual visits involving the WET protocol, including weekly brief assessment of PTSD and mental and physical health. * Then, participants will complete a sixth virtual visit the following week where PTSD, mental and physical health, and treatment feedback are assessed. * Lastly, participants will complete virtual visits 1 and 6 months later involving re-assessment of PTSD and mental and physical health. Therefore, this is a pre-post single group design, where all participants will receive WET to establish initial efficacy and feasibility. Investigators will also consult with an autistic advisory board throughout the project, and make adaptations as recommended in consultation with autistic adults. The goal is to better understand the initial efficacy and feasibility of WET for supporting autistic adults who have experienced trauma.

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.

Adaptation of Written Exposure Therapy in Substance Treatment

The purpose of this pilot non-randomized, uncontrolled clinical trial is to test the feasibility and efficacy of written exposure therapy (WET) for posttraumatic stress disorder (PTSD) as adapted for use within the context of residential substance use disorder (SUD) treatment. All participants meet criteria for PTSD and are in a short term residential SUD treatment program (target residential treatment duration = 28 days) regardless of the research. The main question the study aims to answer is: 1) Is the delivery of adapted WET feasible and acceptable in short term residential SUD treatment for individuals with severe SUD?

Neurobiology of Posttraumatic Stress Disorder Dysfunction and Recovery Following Cognitive Processing Therapy

Posttraumatic stress disorder (PTSD) is a significant personal and societal burden. The purpose of this study is to examine genetic, epigenetic, behavioral, and brain activity changes related to PTSD dysfunction and recovery before and after treatment with Cognitive Processing Therapy.

Integrated CBT to Improve Functioning in Veterans With Anxiety and Substance Use

Individual with anxiety and post-traumatic stress disorder often use alcohol in ways that could cause them harm. Treating both mental health concerns and alcohol use at the same time can help reduce difficulties engaging in multiple treatments. The investigators are evaluating how a cognitive behavioral therapy program that helps Veterans with anxiety, posttraumatic stress disorder, and alcohol use at the same time can help improve the participants lives.

Predicting SSRI Efficacy in Veterans With PTSD

This is a research study to examine the effectiveness of a brief screening method that may predict which people with posttraumatic stress disorder (PTSD) or depression are most likely to show a positive response to selective serotonin reuptake inhibitor (SSRI) medications. Participants will be recruited over approximately 5.25 years, until at least 94 participants complete the 17 week study.

Testing a PTSD m-Health Intervention to Improve Alcohol Treatment Outcomes

The purpose of this study is to learn whether a mobile health application (mHealth App) for posttraumatic stress disorder (PTSD) with brief support can help individuals who are in treatment for alcohol problems.

Adapting and Piloting Behavioral Activation for Veterans With Alcohol Use Disorder and Posttraumatic Stress Disorder

The goal of this clinical trial is to compare an adaptation of Behavioral Activation, a behavioral intervention, to Relapse Prevention treatment, another behavioral intervention, in a sample of U.S. military veterans with co-occurring alcohol use disorder (AUD) and posttraumatic stress disorder (PTSD). The primary aims of this study are to: 1. Adapt Behavioral Activation to treat veterans with AUD/PTSD, 2. Evaluate the feasibility, acceptability, and preliminary effects of Behavioral Activation for AUD/PTSD, and 3. Explore geospatial analysis as a new method for measuring AUD/PTSD recovery. Participants will complete self-report and interview measures immediately before and immediately after treatment. Participants will also be asked to participate in passive geospatial assessment for 14-day periods immediately before and immediately after treatment. Participants will be randomized to treatment condition, which involves 8 sessions of either Behavioral Activation or Relapse Prevention, delivered individually by a trained study therapist.

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).

Brief-intensive CBT Versus Once-weekly CBT in Anxiety-related Disorders

The goal of this clinical trial is to compare brief-intensive cognitive-behaviour therapy (CBT) with regular weekly CBT in people with anxiety-related disorders. The main question to answer is: will brief-intensive CBT improve functioning (work, family, social) more and faster than does regular weekly CBT? Participants will be asked to follow CBT treatment (20 sessions of 45 minutes in both conditions), and participate in 7 measurements with a total duration of 5 hours over 1 year. Researchers will compare: * Brief-intensive CBT: 16 sessions in 2 weeks + 4 follow-up sessions within 3 months * Regular CBT with 20 weekly sessions in 6 months