Clinical Research Directory

IL-33, sST2, and CRP in Panic Disorder

Panic disorder (PD) is characterized by recurrent and unexpected panic attacks and is associated with significant functional impairment. Increasing evidence suggests involvement of immune-inflammatory mechanisms in PD. Elevated levels of inflammatory markers such as C-reactive protein (CRP) have been reported in PD; however, interleukin-33 (IL-33) and soluble suppressor tumorogenicity-2 (sST2), components of the IL-33/sST2 signaling axis, have not previously been investigated in PD. This cross-sectional case-control study aims to compare peripheral serum IL-33, sST2, and CRP levels between drug-naïve subjects diagnosed with PD and healthy controls (HCs). The findings may contribute to understanding the inflammatory mechanisms underlying PD.

A Clinical Trial to Evaluate the Efficacy and Safety of Meltz, a Digital Therapeutic Device, for Improving Panic Symptoms in Patients With Panic Disorder

i. This randomized clinical trial will evaluate the efficacy and safety of Meltz, a digital therapeutic device that provides cognitive behavioral therapy (CBT) for adults with panic disorder. ii. Participants will be randomly assigned to use either Meltz or a sham application. Meltz provides personalized CBT for panic disorder through a smartphone application, while the sham application is similar in appearance and manner of use but does not provide the core therapeutic functions of Meltz. The treatment program is completed within 8 to 10 weeks depending on each participant's treatment progress. iii. This study will evaluate whether Meltz is more effective than the sham application in improving panic symptoms. The primary outcome is the change from baseline to Week 10 in the total score of the Panic Disorder Severity Scale-Self Report (PDSS-SR), a questionnaire used to assess the severity of panic disorder symptoms. The safety of Meltz will also be evaluated based on adverse events reported during the clinical trial.

Effects and Cost-effectiveness of e-Meistring - a Guided Internet-delivered Psychological Treatment

The goal of this observational multicentre study is to address the effectiveness and cost-effectiveness of providing a therapist guided internet based cognitive behavioural therapy (ICBT) for common mental disorders in a routine healthcare setting. Main research questions is 1) What is the effectiveness of guided internet based treatment for moderate depression, panic disorder and social anxiety disorder across clinics in routine care? 2) What is the cost-effectiveness of guided internet based treatment for moderate depression, panic disorder and social anxiety disorder across clinics? 3) Who benefits from guided internet-delivered treatment? 4) What are the predictors of drop-out from guided internet based treatment? 5) To what extent does user experiences of guided internet based treatment influence adherence and effectiveness? Participants will receive up to nine guided ICBT sessions (modules) and answer questionnaires covering symptoms severity, health related quality of life, work and social ability, user satisfaction and medication. All questionnaires are part of the standard patient follow up routines in the four treatment locations participating in the study. Analytical approach is to compare locations/clinics and subgroups of patients.

Exosomal microRNAs as a Biomarker in Panic Disorder and in Response to CBT

Cognitive behavior therapy (CBT) has long been known as an effective treatment for anxiety disorders, either when given by a therapist or when self-administered through a computer program. However, the biological effect of CBT remained largely unexplored. Most studies focused on genomic differences and pursued differences in methylation patterns following CBT, but the findings were very limited in scope, especially when comparing responders and non-responders to CBT. In the currently proposed study, the investigators plan to go one step further and look for changes in exosomal microRNAs (miRs) from serum samples taken before and after CBT from Panic Disorder (PD) patients. Notably, miR changes show a much faster biological response than methylation patterns yet had never been used before in PD research. The primary benefit of this work will be in providing biological validation to psychological treatments. PD is a heavy public health burden, associated with significant market potential for both therapeutic and diagnostic uses.

Psychoeducation Based on Acceptance and Commitment Therapy

The aim of this study is to manage individual psychoeducation in acceptance and commitment therapy for problems with panic disorder and to evaluate the effect of this program on rumination and self-resilience.

Efficacy and Safety of HB-1 for Panic Disorder

The purpose of this study is to determine the safety and efficacy of HB-1, versus placebo and two monotherapies, in male and female adult patients aged 18 to 65 years, inclusive, with Panic Disorder.

The Use of a FDA Cleared, Drug-free, Breathing System for Anxiety and Panic Disorders in Children and Teens

This study will test the efficiency of the Freespira Breathing System in youth.

Evaluation of Family-Based Behavioral Treatments for Youth With Anxiety and Obsessive-Compulsive Disorder

Anxiety and obsessive-compulsive disorders are among the most common in children. Although cognitive behavioral therapy (CBT) is an effective and evidence-based treatment for such disorders, access to CBT is often limited. Family-based and internet-delivered therapy is one method to increase access to care. The purpose of this project is to evaluate the comparative efficacy and treatment mechanisms of two lower-intensity but effective treatments for families of children with anxiety or obsessive compulsive disorder (OCD) via telehealth compared to an adapted Relaxation and Mentorship Training (RMT) intervention involving breathing exercises with a therapist.

Qigong and Multicomponent Exercise in Panic Disorder

Panic disorder is a psychiatric disease characterized by recurrent panic attacks that occur in expected or unexpected situations and create feelings of intense fear, restlessness and discomfort. Panic disorder often has a chronic course, its frequency and severity can be irregular, various physical, mental, and behavioral symptoms can develop, and the quality of life of individuals can decrease significantly. Evidence-based psychotherapy and pharmacotherapy are effective in reducing the symptoms of panic disorder and managing the disorder. However, both of these treatment methods have certain limitations, and approximately one-third of patients do not respond to therapy or the response is not sufficiently effective. Delaying treatment of the disease results in a poor prognosis and more established symptoms. Exercise can be viewed as a low-cost, supportive treatment for relieving symptoms with comparable efficacy to medication and other psychological interventions. Although exercise is recommended for patients with anxiety-panic disorder, there remains uncertainty about whether its effects are sustainable, the type and intensity of exercise required for effective treatment, and thus the effects of qigong and multicomponent exercise on multiple health outcomes in panic disorder. The aim of this study is to examine the effects of Qigong exercise training and multicomponent exercise training on anxiety-panic, balance, mobility, walking, functional strength, physical activity, sleep quality, fatigue, chronic musculoskeletal pain, quality of life and cognition.

Imagery Rescripting for Traumatic Panic Attack Memories

The current project consists of two studies investigating the phenomenological characteristics, centrality levels, and traumatic symptoms of panic attack memories, while testing the effectiveness of the Imagery Rescripting (ImRs) intervention in the treatment of panic disorder. The first study investigates whether panic attack memories share similar phenomenological features, centrality levels, and physiological responses with classic traumatic memories and general negative life event memories in a sample of 152 participants. The second study is a randomized controlled trial (RCT) involving 32 participants diagnosed with panic disorder based on DSM-5 criteria. Participants are randomly assigned to either an Imagery Rescripting (ImRs) intervention group or a control group. The primary objective is to evaluate the clinical effectiveness of a 6-session ImRs protocol in reducing panic disorder symptoms and physiological arousal associated with panic attack memories.

Efficacy of Expectancy Focused Exposure Therapy for Anxiety Disorders

This clinical trial evaluates whether an optimized exposure-based treatment improves long-term outcomes for adults with anxiety disorders. Specifically, it examines whether Expectancy Focused Exposure (EFE), based on the inhibitory learning model, is more effective than Anxiety Focused Exposure (AFE) in reducing anxiety symptoms and preventing the return of fear over time. The study includes adults aged 18 years and older diagnosed with an anxiety disorder, including social anxiety disorder, specific phobia, generalized anxiety disorder, and panic disorder with or without agoraphobia. Anxiety disorders are highly prevalent and can significantly interfere with daily functioning, work performance, and interpersonal relationships. Exposure therapy is a central component of cognitive behavioral treatment for anxiety disorders. Traditional exposure approaches often focus on reducing anxiety during exposure sessions, but many individuals experience a return of fear after treatment. New theoretical models suggest that exposure may be more effective when designed to violate threat expectations and strengthen inhibitory learning. Participants will be recruited in sequential cohorts and randomly assigned to immediate treatment or a brief waitlist before treatment begins. Those assigned to the waitlist will start treatment at the next study step. When treatment begins, participants will receive either EFE or AFE. Both treatments consist of approximately 10 weekly individual psychotherapy sessions delivered by trained therapists. Participants will complete clinical assessments before treatment, during treatment, immediately after treatment, and at 6, 12, and 18 months after treatment completion. In AFE, exposure exercises are organized along an anxiety hierarchy and focus on reducing anxiety responses through repeated confrontation with feared stimuli. In EFE, exposure focuses on identifying and testing threat expectations, and exercises are designed to maximize expectancy violation and strengthen inhibitory learning. Potential risks include temporary emotional discomfort during exposure exercises. All sessions will be conducted by trained clinicians who monitor participant safety throughout the study. The results may help improve exposure-based treatments for anxiety disorders by identifying strategies that enhance long-term outcomes and reduce relapse.

Evaluating Clinical Routines for ICBT

The overall aim of this study is to test the clinical benefits of an AI-based decision support tool (DST) and to evaluate how the DST affects therapists and their patients with depression, social anxiety, or panic disorder during 12 weeks of ICBT.

Testing Delivery Modalities of Team-Based CBT for Pediatric Anxiety in Community Health Settings.

The purpose of this study is to test how the delivery of Cognitive Behavioral Therapy (CBT) for pediatric anxiety and OCD via different methods might increase its availability and effectiveness. CBT involves teaching the patient skills to enable them to gradually come into contact with feared situations. This process of gradually approaching feared situations is called exposure. Although CBT with exposure has the best evidence for treating anxiety disorders, not all children have equal access or respond the same way to CBT. As part of this study, patients will receive weekly CBT treatment sessions involving a combination of weekly visits with an exposure coach and one visit a month with a licensed provider (e.g., social worker) who also provides weekly supervision for the exposure coach. This treatment will be delivered using one of three methods: 1) in-person (face-to-face sessions, occurring in the office and the home/community), or 2) telehealth (entirely remote sessions via web-based video conference), or 3) flexible (individualized mix of in-person and/or telehealth sessions). Eligible participants will be randomly assigned to one of these three methods. Results of this study will help determine which treatment method works best for whom. Treatment as described above will occur as part of care at partnering community care sites in Rhode Island. Providers from the following partnering community care sites will make up patient treatment teams: Blackstone Valley Community Health Care, Family Services of Rhode Island, Gateway Healthcare, Newport Mental Health, and Thrive Behavioral Health. The research study is being conducted by the Pediatric Anxiety Research Center at Brown University Health. The research team will conduct the study assessments that patients will be asked to participate in as study participants. Patients will be asked to complete assessments prior to starting treatment, at two time points during treatment, at the end of treatment, and at two timepoints 3 and 6 months following the end of treatment. Participants will be compensated for their time completing research assessments.

Comparative Effectiveness of Internet-based Versus Parent-Coached Cognitive-Behavioral Therapy For Children and Adolescents With Anxiety and OCD

Anxiety disorders in children and adolescents are common and confer significant disability. Cognitive behavioral therapy (CBT) is the recommended treatment for youth with anxiety, yet many families cannot access CBT due to cost, practicalities of attending in-person treatment sessions, and a shortage of trained providers, especially in rural areas. To combat these barriers, other treatment methods have been developed. Previous research has shown that family-based, internet-delivered CBT (iCBT) for anxiety and OCD in youth has shown a significant reduction in anxiety symptoms. Parent-coached exposure therapy (PCET) focuses entirely on teaching parents and youth together how to address anxiety through the completion of in-session parent-coached exposures and assigning parent-coached exposure as homework in between sessions. Although both iCBT and PCET show positive results in treating pediatric anxiety in comparison to standard-care CBT, little is known about the comparative efficacy of iCBT and PCET. This research is being done to understand the comparative effectiveness of two different types of cognitive-behavioral therapy (CBT) for treating anxiety or OCD in youth.

Mindful Self-Compassion for Anxiety Disorders and Depression

The study will compare 8-week Mindful Self-Compassion training, compared to a control group that does not receive the intervention, on anxiety and depression symptom severity in patients with diagnosed anxiety disorders (generalized anxiety disorder, social anxiety disorder, and panic disorder) or major depressive disorder.

Effectiveness of Cognitive Behavioral Therapy With Panic Control Treatment for Adolescents With Panic Disorder

This study will evaluate the effectiveness of cognitive behavioral therapy with a panic control treatment component in treating adolescents with panic disorder.

Effectiveness of Intensive Cognitive Behavioral Therapy in Treating Adolescent Panic Disorder and Agoraphobia

This study will evaluate the effectiveness of intensive cognitive behavioral therapy in treating adolescents with panic disorder with agoraphobia.

α-N-acetylgalactosaminidase Levels in Panic Disorder

This prospective observational cohort study investigated serum α-N-acetylgalactosaminidase levels in drug-naïve patients with Panic Disorder (PD) at baseline and after six weeks of follow-up and compared them with healthy controls (HC). Associations between enzyme levels, symptom severity, and inflammatory markers were examined. The study aimed to evaluate whether α-N-acetylgalactosaminidase levels are associated with PD symptom severity and inflammatory parameters.

CO2 Reactivity as a Biomarker of Non-Response to Exposure-Based Therapy

Anxiety-, obsessive-compulsive and trauma- and stressor-related disorders reflect a significant public health problem. This study is designed to evaluate the predictive power of a novel biomarker based on a CO2 challenge, thus addressing the central question "can this easy-to-administer assay aid clinicians in deciding whether or not to initiate exposure-based therapy?"

Serotonin Variants & Gut Microbiota in Mental Health

This observational pilot study investigates whether a broad panel of genetic variants relevant to the serotonin pathway (including serotonergic system, methylation cycle, intestinal barrier integrity, and inflammatory response genes) are associated with distinct gut microbiome compositional and functional signatures in adults aged 18-44 years with self-reported mental health conditions (Major Depressive Disorder, Generalized Anxiety Disorder, PTSD, or Panic Disorder). This is a decentralized, participant-funded (Citizen Science) study. Eligible participants provide at-home saliva (buccal swab) and stool samples. Genomic analysis is performed using the NeuroBiologix GenePro+ SNP Panel (Illumina Infinium Global Screening Array-24, \~654,000 SNPs) via Gene By Gene, a CLIA/CAP-accredited laboratory. Gut microbiome analysis is performed by Tiny Health using deep whole-genome shotgun metagenomics (≥20 million reads) on a NextGen Illumina Platform. The study is non-interventional and hypothesis-generating, aiming to identify potential genotype-microbiome associations and estimate effect sizes to inform a future interventional trial. N=30 participants. Study Start: July 2026.

Neurofeedback Enhanced Cognitive Reappraisal Training - Phase 4

This study seeks to understand emotion regulation in those with young adults with anxiety using real-time functional magnetic resonance imaging neurofeedback, a tool that allows individuals to control brain activity. The goal of this project is to understand how receiving feedback about one's own brain activity relates to emotion regulation ability. This work will help the study team understand the brain areas involved in emotion regulation and could lay the groundwork to test if psychotherapy outcomes can be enhanced using neurofeedback. The study hypotheses include: * Participants receiving veritable-Neurofeedback (NF) will show a greater activation increases in the prefrontal cortex (PFC) compared to sham-NF * Participants receiving veritable-NF will show greater cognitive reappraisal (CR) ability compared to those receiving sham-NF * PFC activation will positively correlate with CR ability

A Study to Evaluate Efficacy, Safety, and Tolerability of Darigabat in Participants With Panic Disorder

The purpose of this trial is to measure the efficacy, safety, and tolerability of darigabat (25 milligrams \[mg\] twice daily \[BID\]) compared with placebo in participants with panic disorder.

Mindful Self-compassion for Anxiety and Depression: Impact of Delivery Method

The study will compare the delivery of an 8-week Mindful Self-Compassion training, in-person against video-conference, on anxiety and depression symptom severity in patients with diagnosed anxiety disorders (generalized anxiety disorder, social anxiety disorder, and panic disorder) or major depressive disorder or dysthymia.

Investigation of Pathogenic Gut Microbiota Patterns in Anxiety, Depression and Panic Disorders

This study aims to investigate the etiology of anxiety, depression, and panic disorders, providing new evidence and insights into the root causes and effective treatments, potentially offering a novel approach to achieving complete recovery.