Clinical Research Directory

An Evaluation of the Safety and Efficacy of TSND-201 for the Treatment of PTSD

This study is evaluating the safety and efficacy of TSND-201 in adults with PTSD. Eligible participants will enter a 4-week Treatment Period where they will be randomized 1:1:1 to receive one of two doses of TSND-201 or placebo, once per week. Following the Treatment Period, participants will enter an 8-week Follow-up Period.

Studying the Modification of Attention Bias Remotely After Trauma

The investigators will complete an entirely remote randomized controlled trial (RCT) comparing 14 sessions of attention bias modification (ABM), attention control training (ACT), placebo neutral attention training, and a final control condition with daily questions in 1,897 individuals with clinically significant Post-traumatic Stress Symptoms (PTSS) (defined as PCL-5 score ≥ 33). To assess effects of the training and control conditions, the investigators will administer tests of threat-related attention bias and variability, and self-report assessments of PTSS, depression, anxiety, and perceived stress at baseline, after one and two weeks of training, and at eight-week follow up. The investigators plan to screen and confirm interest from over 3,000 eligible participants over a period of 24 months to enroll and randomize 1,897 participants with the end goal of 1,232 completers (176 per condition).

An Evaluation of the Safety and Efficacy of Methylone for the Treatment of PTSD

This study is evaluating the safety and efficacy of methylone in adults with PTSD. The study is conducted in two parts. * Part A is open-label and will enroll up to 15 participants with PTSD * Part B is randomized (1:1:1), single-blind and will enroll up to 45 participants with PTSD Eligible participants will enter a 3-week Treatment Period (Part A) or 4-week Treatment Period (Part B) where they will receive methylone once weekly. Following the Treatment Period, participants will enter a 6-week Follow-up Period (Part A) or 8-week Follow-up Period (Part B).

Goal-Directed Sedation in Mechanically Ventilated Infants and Children

Ventilated pediatric patients are frequently over-sedated and the majority suffer from delirium, a form of acute brain dysfunction that is an independent predictor of increased risk of dying, length of stay, and costs. Universally prescribed sedative medications-the GABA-ergic benzodiazepines-worsen this brain organ dysfunction and independently prolong duration of ventilation and ICU stay, and the available alternative sedation regimen using dexmedetomidine, an alpha-2 agonist, has been shown to be superior to benzodiazepines in adults, and may mechanistically impact outcomes through positive effects on innate immunity, bacterial clearance, apoptosis, cognition and delirium. The mini-MENDS trial will compare dexmedetomidine and midazolam, and determine the best sedative medication to reduce delirium and improve duration of ventilation, and functional, psychiatric, and cognitive recovery in our most vulnerable patients-survivors of pediatric critical illness.

OSA PAP Treatment for Veterans With SUD and PTSD on Residential Treatment Unit

Substance use disorder (SUD) and posttraumatic stress disorder (PTSD) frequently co-occur and having both disorders is associated with greater psychological and functional impairment than having either disorder alone. This is especially true in residential settings where both disorders are more severe than outpatient settings. Obstructive sleep apnea (OSA) is highly comorbid with both disorders and untreated OSA is associated with worse functional impairment across multiple domains, worse quality of life, worse PTSD, higher suicidal ideation, and higher substance use and relapse rates. Treating OSA with evidence-based positive airway pressure (PAP) in Veterans with SUD/PTSD on a residential unit is a logical way to maximize treatment adherence and treatment outcomes. This study compares OSA treatment while on a SUD/PTSD residential unit to a waitlist control group. The investigators hypothesize that treating OSA on the residential unit, compared to the waitlist control, will have better functional, SUD, and PTSD outcomes.

Mindfulness-based Psilocybin Therapy for PTSD

The goal of this study is to learn how psilocybin delivered with mindfulness-based therapy may help symptoms of posttraumatic stress disorder (PTSD). This is an assessor-blinded, randomized, controlled study in participants with PTSD. The study will investigate the changes in brain activity, connectivity, and microstructural neuroplasticity assessed using EEG/EMG and multimodal MRI measures after administration of one oral dose of psilocybin, accompanied either with standard "psychological support" only; or with standard support plus Mindfulness-based Cognitive Therapy (MBCT).

Body-oriented Psychotherapy for Individuals With a History of Child Maltreatment and Trauma-related Symptoms

This Pilot Randomized Controlled Trial (RCT) overall aim is to establish the safety, feasibility, acceptability and preliminary effects of a body-oriented psychotherapy, Somatic Experiencing (SE), on social functioning and mental health among adults with a history of Child Maltreatment (CM) and symptoms of posttraumatic stress disorder (PTSD) or complex posttraumatic stress disorder (CPTSD). Participants will be randomized either to an SE-group (n=25, psychoeducation, and information about treatment possibilities + 15-session SE treatment) or to a control group (n=25, same psychoeducation and information about treatment possibilities + regular phone calls to provide updates on their well-being and if they started a treatment). Given the lack of research on the effect of SE on Psychological Safety in this population, while SE has not yet been introduced into the Swedish health care system, special consideration will be given to participant safety, feasibility and acceptability of the SE-treatment. This includes monitoring (and assessing) for serious adverse events (SAEs) and adverse events (AEs), if conducting an RCT on SE in our target sample is feasible (e.g., achieving the target sample goal, assessing attrition rates and session attendance) and the acceptance of the used SE intervention (e.g., positive evaluations and willingness to recommend the treatment). Next to assessing safety, feasibility and acceptability, preliminary outcomes (self-report and experimental measures) will be evaluated at pre-treatment, post-treatment (20 weeks after pre), and at a 20-week follow-up, assessing primary outcomes (Psychological Safety) and secondary outcomes (Social Safeness, PTSD, CPTSD, Depression), as well as additional factors (e.g., interoception) that could contribute to decreased mental health and social functioning issues. Additionally, participants' behavioral (e.g., interpersonal distance) and physiological responses (HR, HRV, EDA) to social stimuli will be assessed pre- and post-treatment in an experimental setup to explore SE's potential to reduce Negative Affect and increase Positive Affect (Activated, Relaxed, Safe/Content) in response to social stress.

Neuromodulation and Neurorehabilitation for mTBI

This study will determine (i) the magnitude of immediate and sustained effects of a current clinical standard interactive computer attention processing training (APT) when combined with intermittent theta burst stimulation (iTBS), a type of repetitive transcranial magnetic stimulation and (ii) determine how APT + iTBS changes the neurocognitive system of attention in individuals with persistent attention deficits related to mTBI +/- PTSD.

Preliminary Effectiveness of Hybrid Individual and Group MDMA-assisted Therapy for War-related PTSD

The overall objective of this study is to use standard clinical measures to explore the safety and preliminary effectiveness of open-label MDMA-assisted therapy with a flexible dose of methylenedioxymethamphetaminel, in participants with war-related Post traumatic Stress Disorder, in a hybrid individual and group treatment protocol. The overall safety objective is to assess the severity, incidence, and frequency of AEs, AEs of Special Interest (AESIs), and Serious Adverse Events (SAEs), concomitant medication use, suicidal ideation and behavior and vital signs .

Determining the Right Acupuncture for Good Recovery Over Neuropsychiatric Trauma

This study seeks to verify that a specific acupuncture treatment is effective at reducing symptoms of neuropsychiatric trauma found in those diagnosed with Post-Traumatic Stress Disorder (PTSD).

Cognitive Control Training for Extinction in PTSD

The proposed study will test whether a working memory training (WMT) program improves fear extinction learning and its underlying neural circuitry in Veterans with posttraumatic stress disorder (PTSD). WMT is designed to improves the ability to maintain task-relevant information in mind. The project will further validate the relationship between working memory and fear extinction using novel computational and multivariate analyses that link to specific PTSD symptoms. If WMT can enhance fear extinction learning, then WMT may be a powerful adjunctive treatment that can enhance exposure therapy outcomes or be leveraged as a stand-alone treatment. This project supports the Department of Veteran Affairs mission of developing viable targets of treatment for Veterans with PTSD.

Non-invasive Vagus Nerve Stimulation (nVNS) for Post-Traumatic Stress Disorder (PTSD)

The goal of this clinical trial is to evaluate the safety and effectiveness of the gammaCore non-invasive vagus nerve stimulation (nVNS) device as an additional treatment for symptoms of post-traumatic stress disorder (PTSD) in adults. The vagus nerve connects the brain with many organs and systems in the body and plays a role in regulating stress and emotional responses. The gammaCore device is a handheld, rechargeable medical device that delivers gentle electrical stimulation to the vagus nerve through the skin on the side of the neck. By stimulating this nerve, the device may help reduce PTSD symptoms. gammaCore is cleared by the U.S. Food and Drug Administration (FDA) for the treatment and prevention of migraine and cluster headache. It has not yet been approved for the treatment of PTSD. This study is being conducted to better understand whether this type of stimulation may help improve PTSD symptoms and to evaluate its safety when used for this purpose. The main questions this study aims to answer are: * Is non-invasive vagus nerve stimulation safe for people with PTSD when used regularly at home? * Does treatment with the gammaCore device improve PTSD symptom severity over time? In this study, approximately 40 adults with PTSD will participate in an open-label pilot study. Participants will first complete a 4-week baseline period in which their PTSD symptoms are monitored. This allows researchers to understand each participant's symptoms before starting the intervention. Participants will then begin a 12-week treatment period using the gammaCore device at home. During this time, participants will apply the device to the side of the neck for short stimulation sessions each day as instructed by the study team. Participants will attend six study visits, some conducted remotely and some in person. These visits include screening, training on how to use the device, and follow-up assessments. During the study, participants will complete questionnaires and clinician-administered assessments that measure PTSD symptoms and quality of life. Researchers will also monitor participants for any side effects or medical problems related to the device. By collecting information on symptoms, safety, and device use, this study will help researchers understand whether non-invasive vagus nerve stimulation could become a useful treatment option for people living with PTSD.

Identification of Physiological Sleep Indices That Reflect Clinical Improvement and Reduction in Stress Biomarkers After Stellate Ganglion Block in Patients With Posttraumatic Stress Disorder (PTSD)

Post-traumatic stress disorder (PTSD) is a chronic disorder that develops following exposure to trauma, and is characterized by intrusive experiences, avoidance, cognitive-emotional changes, and hyperarousal. It is based on a complex noradrenergic dysregulation. The amygdala activates the hypothalamus to release excessive corticotropin releasing factor (CRF), which activates the hypothalamic-pituitary-adrenal (HPA) axis and leads to high nocturnal cortisol levels with EEG changes and increased arousals. At the same time, the Locus Coeruleus (LC) releases excess norepinephrine (NE), which interferes with the transition to Non-REM sleep and suppresses the stability of REM sleep, a stage essential for emotional processing and the extinction of conditioned fear. Sleep disturbances occur in 70-90% of PTSD patients, leading to fragmented sleep that impairs conditioned fear extinction, reinforces hyperarousal, and perpetuates the disorder as a protective-morbidity mechanism \[1,2\]. Beyond the clinical implications, sleep disturbances mediate the relationship between PTSD and functional disability and occupational disability, with 74% of the economic burden of PTSD in Israel attributed to loss of employment and productivity (3,4). The Stellate Ganglion (SG), located between the C6-C7 vertebrae, is a central sympathetic junction between the central nervous system and the periphery. This connection is expressed in descending pathways from the amygdala and prefrontal cortex (PFC) and ascending pathways from the periphery through the SG that feed the LC, which in turn secretes NE to the amygdala and other limbic areas and affects fear and memory processing. Subganglionic ganglion block (SGB) using local anesthetic injection reduces sympathetic tone, reduces Nerve Growth Factor (NGF) and NE levels, and "breaks" the pathological feedback loop. This effect was found to reduce conditioned fear memory and was accompanied by a significant decrease in NE concentration in the amygdala (5,6). A multicenter RCT showed that SGB led to an improvement in PTSD symptoms, with sleep disturbances and hyperarousal being the most responsive symptoms \[7\]. This finding was supported by a recent meta-analysis that confirmed a significant improvement in key sleep measures, including total sleep time and overall sleep quality (8). A RCT that included a sleep laboratory and neurotransmitter measurements in anxiety patients with sleep disorders found that SGB led to a decrease in NE and an increase in Serotonin- and NPY-, along with an objective improvement in quality and time of wakefulness \[9\]. Initial findings in primary insomnia patients without PTSD also showed significant improvement, and combining SGB with CBT-I (cognitive-behavioral therapy) yielded stable results over time \[10\]. These findings strengthen the rationale for using SGB as a treatment for disorders resulting from sympathetic overactivity and HPA axis dysregulation. Despite this promising evidence, there is a knowledge gap: the effect of SGB on objective and continuous sleep measures in a natural setting has not yet been examined, and cortisol levels have not been measured concurrently with changes in sleep. Polysomnography (PSG)-the standard test for diagnosing sleep disorders-is not suitable for continuous monitoring due to discomfort. Wearable devices, in particular the Oura Ring Gen3, have been shown to be a valid alternative to PSG for sleep monitoring in a natural setting. The ring, which demonstrated the highest PSG compliance among consumer monitoring devices, combines accelerometry and photoplethysmography (PPG) to continuously measure WASO (Wake After Sleep Onset), Sleep efficiency (SE), Heart rate variability (HRV), sleep stages, and nocturnal heart rate (11,12). The proposed study aims to bridge this gap, to monitor for the first time objective physiological sleep measures and cortisol levels over time in PTSD patients after SGB. In addition to its contribution to understanding the mechanism of action of SGB, this study will isolate the physiological measures associated with clinical improvement and may serve as a gateway for further research and treatments in the field and for therapeutic success in PTSD and autonomic dysregulation.

Remotely Resolving Psychological Stress (Remote RePS)

The investigators have developed a mobile app called Resolving Psychological Stress (REPS) for people with posttraumatic stress disorder (PTSD). The app will administer threat-related attention bias modification to individuals who score high on a PTSD checklist. This study will be administered remotely to individuals in the United States. The aims of the study are to explore feasibility, acceptability and usability of the app in an entirely remote study, as well as to explore the efficacy of the app at reducing attention bias and PTSD symptom severity.

Psilocybin-Assisted Cognitive Processing Therapy for Chronic PTSD

This is an open-label trial evaluating feasibility, tolerability, safety and efficacy of psilocybin assisted cognitive processing therapy for chronic Posttraumatic Stress Disorder (PTSD).

Innovative Multimodal and Attention Training to Improve Emotion Communication in Veterans With TBI and PTSD

Poor emotion recognition has been associated with poor quality of interpersonal relationships, loss of employment, behavioral problems, reduced social reintegration, social isolation and even suicide. Deficits in emotion recognition are common in traumatic brain injury (TBI) and in post-traumatic stress disorder (PTSD) but these deficits have not been well studied in Veterans with both mild TBI (mTBI) and PTSD. Currently there are no interventions for emotion recognition in Veterans with mTBI and PTSD, and interventions for severe TBI have lacked training of both facial and vocal emotion recognition. In a preliminary study of an innovative combination of facial and vocal modalities, a multimodal affect recognition training (MMART) showed promise but lacked attention training that is an essential component in recognizing emotions in our daily lives. Given the need to improve relationships and productivity in Veterans with mTBI and PTSD, a study is needed to determine the effectiveness of a MMART combined with attention training.

Evaluation of a Trauma-Informed Partner Violence Intervention Program

The goal of this study is to conduct a randomized controlled trial (RCT) comparing outcomes between two programs to reduce intimate partner violence (IPV)- the Strength at Home (SAH) program and a standard, state-approved IPV intervention program, Treatment as Usual (TAU). Primary outcomes will include self- and partner-reported physical and psychological IPV. Secondary outcomes will include self-reported PTSD symptoms, alexithymia, alcohol use problems, and treatment satisfaction, assessed across five time points.

Anger, Social Cognition and Post-traumatic Stress Disorder in Former French Military Personnel

This is a single-center cross-sectional study conducted on a sample of former military personnel who had been diagnosed with PTSD. The main objective of this study is to test a mediation model positing that PTSD increases individuals' levels of anger through its detrimental effect on social cognitive abilities (Quantitative component). The secondary objectives focus on the impact of alcohol consumption and ACE on the three components (theory of mind, emotional decoding, empathy) of social cognition (qualitative component). A second secondary objective aims to explore the moral harms reported by former military personnel through a qualitative analysis of semi-structured interviews (qualitative component). Primary Objective (Quantitative Component): To examine the links between PTSD, anger, and social cognition among French veterans using mediation analyses. The aim is to test whether PTSD (independent variable) indirectly influences individuals' levels of anger (dependent variable) through its effect on social cognition (mediating variable). Secondary Objectives: * Quantitative component: to examine other factors associated with PTSD that may influence social cognitive abilities, such as alcohol consumption and experiences of childhood abuse (Abuse Childhood Experience-ACE); * Qualitative component: to explore the psychological trauma experienced by military personnel through a qualitative analysis of semi-structured interviews. Evaluation criteria: Main Components: Quantitative Component Self-report scales for PTSD, anger, and empathy, as well as two social cognition tasks: * PCL-5 - Posttraumatic Checklist-5 * STAXI-2 - Spielberger's State-Trait Anger Expression Inventory-2 * EQ - Empathy Quotient * MASC - Movie for the Assessment of Social Cognition * TREF - Facial Emotion Recognition Test Secondary: 1. Quantitative component Self-reported scales of alcohol use, childhood abuse experiences, and anxiety and depression: * AUDIT - Alcohol Use Disorders Identification Test * ACE-IQ - Adverse Childhood Experiences-International Questionnaire * HADS - Hospital Anxiety and Depression Scale 2. Qualitative component - Content of verbatim transcripts from semi-structured interviews

Cognitive Processing Therapy for Posttraumatic Stress Disorder and Co-occurring Lived Experience Stress

Populations facing health disparities include groups with significantly higher rates of posttraumatic stress disorder than the general population who frequently experience lived experience stress, which may complicate posttraumatic stress disorder symptom presentations. However, there are currently no posttraumatic stress disorder treatments designed to meet the unique needs of these individuals. The proposed study will pilot an adaptation of Cognitive Processing Therapy (a gold-standard treatment for posttraumatic stress disorder) that has been modified to incorporate the impact of lived experience stress as an additional treatment target. This project has the potential to advance our understanding of how to enhance Cognitive Processing Therapy in order to optimize posttraumatic stress disorder treatment response and mitigate health disparities.

Efficacy of a Brief Intervention to Improve Sexual and Gender Minorities' Mental Health: Randomized Controlled Trial.

Experiences of violence, from micro to physical aggressions, have a deleterious impact on mental health. According to the Minority Stress Theory, unfavorable social conditions (such as anticipated and experienced discrimination and internalized homophobia), mediated by resilience strategies, can lead to mental health or illness. Sexual and gender minorities (SGM) face stigma and discrimination aggravating multiple aspects of their lives: from school drop-out to halting health care access. SGM reveal avoiding medical assistance for fear of discrimination while health professionals disclose feeling unprepared to handle SGM health needs. There are two main challenges: 1) developing specific psychological interventions to reduce the impact of stigma and discrimination on SGM' mental health; and 2) training public health professionals to properly address SGM needs. Therefore, the present trial aims to assess the efficacy of a brief, self-guided, on-line, asynchronous and unsupervised psychological intervention in improving SGM' mental health.

Randomized Controlled Trial of Treatment to Optimize Heart Rate Variability for Persistent Post-Concussion Symptoms

Many combat veterans (c-Vs), service members (SMs) and civilians with mild traumatic brain injury (mTBI, also termed concussion) suffer from persistent post-concussion symptoms (PPCS) that degrade physical and cognitive well-being and have been linked with early neurodegeneration. PPCS include somatosensory (e.g., headache, disturbed vision), vestibular (e.g., dizzy, clumsy), cognitive (e.g., executive function, memory) and affective symptoms (e.g., sleep disturbance, irritability, depression). A key pathological process that provokes and perpetuates PPCS is autonomic nervous system (ANS) dysfunction such as unremitting sympathetic nervous system activation that also exacerbates other pathology such as inflammation. ANS activity can be readily quantified by measuring heart rate variability (HRV), or the variation in heart rate over time, which serves as a valid index of both physiological and psychological health

Multifaceted Intervention to Restore Resilience and Overcome Risk

The MIRROR study will compare the effectiveness of two interventions in improving emotion regulation and reducing PTSD symptoms in female Veterans with military sexual trauma (MST) and/or intimate partner violence (IPV) and co-occurring brain injury.

An Evaluation of the Safety and Efficacy of TSND-201 for the Treatment of PTSD (EMPOWER-1)

This study is evaluating the safety and efficacy of TSND-201 in adults with PTSD. Eligible participants will enter a 4-week Treatment Period where they will be randomized 1:1:1 to receive one of two doses of TSND-201 or placebo, once per week. Following the Treatment Period, participants will enter an 8-week Follow-up Period.

A Hybrid 1 Effectiveness-Implementation Trial of Partner-Assisted Prolonged Exposure for PTSD

PTSD occurs in up to 17% of post-9/11 US Service Members and is associated with long-term functional impairment, family problems, unemployment, and suicidality. Trauma-focused therapies (TFTs), such as Prolonged Exposure (PE), result in significant relief for many. Yet, TFTs are not equally effective for everyone. An important minority (\~40%) will retain their PTSD diagnoses after treatment, and many discontinue treatment prematurely, especially post-9/11 Service Members. TFTs are also more effective in addressing symptoms than psychosocial functioning. More work is needed to improve the consistency and potency of TFTs. Partnering with significant others may provide a powerful method for helping individuals get more out of their PTSD treatment. Observational research shows that relationship factors can help patients initiate, stay in, and experience greater benefit from PTSD treatment. Veterans that were surveyed experienced greater treatment gains when they shared more about their treatment with loved ones and when loved ones accommodated less for PTSD symptoms. Despite the promise of partner-involved interventions, there is no couples approach to PTSD treatment that has demonstrated superior outcomes to individual-only treatment models (i.e., TFTs). To address this gap, the investigators have completed a series of partner-assisted PTSD treatment studies, leading up the current proposal (Partnered PE, PPE). The investigators found that treatment completion rates were better than routine clinical care, and the treatment led to large improvements in participants' functioning, PTSD symptoms, and romantic functioning. For this proposed study, the primary objective is to conduct a randomized controlled trial (Research Level 3; larger-scale clinical trial) to test the superiority of PPE to standard PE among post 9/11 Veterans. The investigator's primary hypothesis is that PPE will lead to greater improvements in psychosocial functioning than standard PE. Secondary and tertiary aims examine posttreatment clinical outcomes (PTSD, depression) and intimate partner outcomes (relationship functioning, distress, caregiver burden, and psychosocial functioning), as well as examine strategies for PPE implementation. In exploratory aims, the investigators will examine the stability of group differences, treatment completion rates, the role military sexual trauma history, and treatment mechanisms.