Active clinical trials for "Stress Disorders, Post-Traumatic"

Every year, approximately 2 million people in the United States and 280,000 in Canada experience a mild traumatic brain injury/concussion. In patients with concussion, symptoms experienced following injury usually get better within 3 months. However, approximately 5-25% of people will experience symptoms beyond the 3 month period, characterized by persistent headaches, fatigue, insomnia, anxiety, depression, and thinking or concentration problems, which contribute to significant functional impairment. Chronic headache is the most common symptom following concussions. They can last beyond 5 years following injury, significantly impacting daily activities. To date, post-concussion symptoms have no known "cure". One potential approach to treating post-concussion symptoms may involve using drug-free interventions, such as neuromodulation therapy. This has the goal of restoring normal brain activity. Repetitive transcranial magnetic stimulation (rTMS) is one method currently being explored as a treatment option. TMS is a procedure where brain electrical activity is influenced by a magnetic field. Numerous studies using rTMS to treat other disorders, such as dementia, stroke, cerebral palsy, addictions, depression and anxiety, have shown much promise. The primary objective of this study is to determine whether rTMS treatment can significantly improve persistent post-concussion symptoms. A secondary objective is to explore the relationship between potential changes in brain function and clinical markers associated with rTMS treatment and how functional near-infrared spectroscopy (fNIRS), a neuroimaging technology, may be used to assess rTMS-treatment response.

The proposed project seeks to demonstrate the engagement of post-exposure dopamine neurotransmission and downstream acute reorganization of dopaminergic resting-state neural networks as a means of increasing consolidation of extinction memories formed during analogue exposure therapy in adult women with PTSD. Participants will include 120 women aged 21-50 with a current diagnosis of PTSD related to physical or sexual assault, English speaking, and medically healthy. Participants will complete the stages of the study across 2-3 days, depending on participant need.

Recent estimates suggest that over 610,000 US Veterans treated by the Veterans Health Administration (VHA) suffer from PTSD, a disorder that can be chronic and debilitating. The heterogeneity of the 20 symptoms of PTSD; comorbidity with disorders such as depression, panic, and substance use; high rates of lingering effects of physical injury; and suicidality all contribute to complex clinical presentations and can exact a significant toll on functioning, quality of life, and well-being even decades after exposure to the traumatic event. Perhaps spurred by the President's New Freedom Commission on Mental Health, psychosocial rehabilitation has shifted from the periphery in mental health recovery models to a more primary focus in clinical settings, including recommendations for use of psychosocial rehabilitation techniques in trauma-focused mental health care. Support for the efficacy of psychosocial rehabilitation techniques in PTSD recovery programs has burgeoned in recent years and data supporting psychological treatments for PTSD has increased exponentially, yet the two approaches to recovery have largely remained independent. Cognitive Processing Therapy (CPT), the evidence-based psychotherapy (EBP) for PTSD most frequently delivered within VHA, yields large magnitude reductions in primary PTSD outcomes. Corresponding gains in occupational, social, leisure, and sexual functioning, and in health-related concerns have also been demonstrated. Despite CPT's effectiveness, there is room for improvement in overall outcomes and patient engagement. Further, improvements in functioning and quality of life are more modest than those observed in PTSD and associated mental health symptoms. Prior work suggests that unaddressed difficulties in functioning contribute to premature dropout from EBPs for PTSD among Veterans. Directly targeting impairments associated with psychosocial functioning has the potential to substantially increase the scope of recovery beyond the core symptoms of PTSD and facilitate greater patient engagement, resulting in more Veterans benefitting from CPT. Modifying the CPT protocol to personalize the intervention for the individual patient has resulted in better overall response rates for a wider variety of patient populations suffering from complicated clinical presentations. Case formulation (CF) is a well-established approach to cognitive-behavioral treatment that facilitates a collaborative process between providers and patients to guide the tailoring of treatment to meet idiosyncratic patient needs. Integrating CF strategies into the existing CPT protocol will enable providers to personalize CPT to directly address impairment in functioning as well as provide the latitude to directly intervene with the complex challenges that threaten optimal outcomes within the context of trauma-focused therapy. CF-integrated CPT (CF-CPT) expands and enhances the CPT protocol to facilitate a personalized and flexible approach to treating PTSD that prioritizes the administration of the full dose of CPT while expanding the protocol to directly target important domains of functioning and result in more holistic outcomes. This controlled treatment outcome trial will randomize a national sample of CPT providers (Veteran n = 200; provider n = 50) to either deliver CF-CPT or CPT to compare the relative effectiveness of CF-CPT to CPT in improving primary outcomes, including Veterans' psychosocial functioning, quality of life and well-being over the course of treatment and 3-month follow-up as compared to Veterans who receive standard CPT. Further, Veterans who receive CF-CPT will demonstrate greater reductions in PTSD and depression over the course of treatment and 3-month follow-up than those who receive CPT. This study also seeks to determine the effectiveness of CF-CPT as compared to CPT in improving Veterans' treatment engagement (CF-CPT will demonstrate higher rates of Veteran treatment completion than CPT). This study will valuate CF-CPT's indirect impact on Veterans' psychosocial functioning and PTSD/depression symptomology Change in functioning, quality of life, and well-being & PTSD and depression will be associated with improvement in the idiosyncratic clinical challenges targeted by the CF. This study will also examine between-group differences across secondary outcomes (e.g. anger, anxiety, health concerns, sleep, numbing/reactivity) and describe the frequency and type of the clinical and rehabilitative needs of the Veterans and the type and duration of divergences (e.g. rehabilitative techniques) made by providers.

There is large body of evidence demonstrating that Posttraumatic Stress Disorder (PTSD) is associated with alterations in the stress hormone cortisol. There is also evidence that medications that block cortisol may be beneficial for treating PTSD and depression. The VA recently completed a study of a mifepristone, a medication that blocks cortisol and progesterone hormones, and found some benefit for Veterans who did not have a history of traumatic brain injury. The proposal will test a medication from a new class of cortisol blockers which have no effect on progesterone. The proposed study will test the drug CORT108297 for treatment of PTSD and will establish a safety profile that will inform the design of future studies.

Despite the VA's best efforts to treat the psychosocial impact of war, many combat Veterans report lingering difficulty reintegrating into meaningful post-deployment lives. War is among the most extreme forms of human experience but, for many, wartime trauma was treated using models transported from civilian single-incident trauma contexts. Veterans have unique needs and experiences that require culturally responsive and sensitive conceptualizations and treatments. Patient-centered care is improved by providing multiple effective treatment options and this project, if successful, could have a significant impact on VA care. This CDA-2 project has the potential to offer innovative treatment for traumatized combat Veterans who otherwise may not find full relief from PTSD. Clinical research practice will be advanced by employing state-of-the-art user-centered design methods combined with expert clinical feedback to develop an effective and usable group treatment manual that will meet VA needs.

Sexual assault can lead to devastating consequences including the development of chronic conditions including posttraumatic stress disorder (PTSD) and alcohol use disorders (AUD). Interventions delivered soon after exposure to assault can decrease the long-term negative consequences of sexual assault but existing interventions are limited in their ability to target concurrent PTSD symptoms and alcohol use and little is known about how to make best practice treatment decisions in the early period following sexual assault. A greater emphasis on transdiagnostic processes that are related to both PTSD and alcohol use, such as fear and reward systems, can elucidate mechanisms of recovery, lead to the development of more effective intervention approaches, and guide clinical decision making for patients recently exposed to sexual assault.

The overarching goal of the proposed project is to evaluate a randomized clinical trial of the Pregnant Moms' Empowerment Program aimed at detecting its effects on maternal mental health, re-victimization, parenting sensitivity, and infant development. The project also seeks to examine theoretically-grounded mechanisms of change, including social support and empowerment. Women participating in the study will receive either the PMEP or participate in a contact-equivalent active control group during pregnancy, and will be interviewed at baseline, post-intervention and with their infants at 3 months and 1 year old. The study will occur at two sites - the University of Notre Dame and the University of Memphis. Participants will be recruited from the local community at both locations, with an equal number of women drawn from each site - Memphis, Tennessee (n=115) and South Bend, Indiana (n=115). Enrollment will continue for approximately 2.5 years, with an expected rate of 8 eligible women per month, based on a pilot study of the Pregnant Moms' Empowerment Program. The expected duration of the study for each participant will be approximately 1.5 years, with some variation due to women enrolling at different points in their pregnancy. The primary objective of the proposed project is to determine if the Pregnant Moms' Empowerment Program has positive effects on maternal mental health, re-victimization rates, parenting sensitivity, and infant development compared to women's participation in a contact-equivalent active control group. This objective will be evaluated using a multi-site randomized clinical trial design. Participants (N = 230) will be equally randomized into study arms. Eligible women will include those who are: 1) currently pregnant (primi or multiparous) and between 10 and 30 weeks gestation, 2) experienced IPV within the past year, 3) English speaking and 4) age 16 or older. The study will include 9 total visits: 4 assessments and 5 sessions for both study arms. In-person assessment visits will be completed by a trained research assistant; each visit will take approximately 2-3 hours, with post-partum assessments somewhat longer than prenatal assessments given the addition of the infant developmental assessment and parent-child observation task. Women will be compensated $30 for the first two assessments and $50 for the second two assessments. Following the final assessment, women will be invited to complete a daily diary (virtually) each day for 30 days. Each survey will take approximately 5-10 minutes to complete, and women will be compensated $2 for each completed survey. Women will also receive a $10 bonus for each set of 10 consecutive surveys. Treatment sessions will be 2 hours in duration. Women in the PMEP will complete a structured set of sessions: (1) supporting each other, support in the community, (2) identifying and understanding sources of distress, (3) cognitive and behavioral strategies to build resilience and resolve conflict, (4) perinatal health and infant care, and (5) positive parenting. Women in the active control condition will participate in facilitated discussions on a topic identified by the group. All sessions will be audio recorded so that treatment fidelity can be evaluated (for the Pregnant Moms' Empowerment Program) and so that content overlap can be assessed (for the active control condition).

Trauma-related guilt is common and impairing among trauma survivors, particularly among Veterans with posttraumatic stress disorder (PTSD). The investigators' work shows that a brief treatment targeting trauma-related guilt, Trauma Informed Guilt Reduction Therapy (TrIGR), can reduce guilt and PTSD and depression symptoms. Whether TrIGR is no less effective than longer, more resource heavy PTSD treatments disseminated by by VA, like cognitive processing therapy (CPT), is the next critical question that this study will seek to answer. 158 Veterans across two VA sites will be randomized to TrIGR or CPT to evaluate changes in PTSD, depression, guilt and shame symptoms across the two treatments.

Study to provide evidence of efficacy for Rapid Resolution Therapy in symptoms of PTSD, Anxiety, and Depression in survivors of sexual violence.

Post-traumatic stress disorder (PTSD) refractory to treatment is marked by failure of fear extinction and its biological substrate, amygdala reactivity to trauma reminders. Decades of research have clarified the neuronal mechanisms coordinating fear extinction and consolidation. Fear cells and extinction cells in the basolateral amygdala (BLA) alter their firing rate based on the nature of the stimulus and the influence from the medial prefrontal cortex (mPFC) and the ventral hippocampus (vHPC). Together, the BLA, mPFC, and the vHPC form an anxiety-processing network where the BLA links stimulus to emotion, the vHPC provides memory context, and the mPFC coordinates extinction or consolidation. Local field potential (LFP) recordings from the BLA have revealed specific signals that correspond to an enhanced fear state. Previous studies have shown that neuromodulation of the BLA can promote extinction in a rodent model and in a treatment-refractory PTSD patient. This action is likely carried by disrupting fear signals within the BLA; however, continuous neurostimulation may also disrupt normal function of the amygdala. The present application proposes to investigate the use of Responsive Neurostimulation (RNS, Neuropace) in six (6) veterans suffering from severe treatment-resistant PTSD. This dual-activity device will allow us to chronically record LFPs from the BLA under specific conditions such as fear conditioning, exposure to trauma reminders, and emotional memory encoding and retrieval. In addition, the neural activity will be captured during real-life symptoms of flashback and nightmares. These recordings will provide the specific electrophysiological biomarkers of hypervigilance and re-experiencing. The device will then be programmed to detect and treat these biomarkers with a pre-determined electrical pulse. The patients will be followed prospectively using psychological scales but also with functional neuroimaging and electroencephalograms. These modalities will be used to determine the extent of circuit engagement as a result of the therapy. By approaching PTSD from a fear processing mechanism perspective, our project will serve as a proof of concept for other circuit-based therapies in psychiatry. This proposal is a multi-departmental effort involving 11 investigators across 7 departments and requires a close collaboration between clinical and basic scientists. As a result, the findings underlying chronic recordings will bridge the basic science results from fear conditioning research to clinical neural processes in PTSD patients.