Clinical Research Directory

Focused Ultrasound for Behavioral Health

This is a double-blind, within-participant crossover, multi-site dose-finding study evaluating the safety, feasibility, and preliminary efficacy of repeated low-intensity focused ultrasound (LIFU) stimulation using the ATTN201 device across seven candidate deep-brain targets in adults with subsyndromal-to-moderate depression, anxiety, or obsessive-compulsive disorder. Every session delivers active ATTN201 stimulation; there is no sham or placebo condition. Participants and the on-site study staff who deliver stimulation and administer the clinical scales are blinded to the brain target and to the stimulation parameters assigned for each session by a constrained Bayesian optimization algorithm.

Gamified Combined Cognitive Bias Modification in Adults Diagnosed With OCD: Randomized Controlled Trial

This randomized controlled trial examines the effects of a mobile-based gamified combined cognitive bias modification (CBM-C) intervention on obsessive-compulsive symptoms, obsessive beliefs, attentional and interpretation biases, depressive symptoms, and psychological distress. The gamified CBM-C condition is compared to a standard mobile-based CBM-C and a placebo control condition. All interventions are delivered via a mobile application. Assessments are conducted at baseline, post-intervention (week 4), and 3-month follow-up.

Artificial Intelligence-Powered Virtual Reality Exposure Therapy for OCD in College Students: A Proof-of-Concept Study

This research study is being conducted to study the use of artificial-intelligence powered virtual reality exposure therapy (AI-VRET) to treat college students with obsessive compulsive disorder (OCD).

Low-intensity Ultrasound for Individuals With Obsessive-compulsive Disorder

The goal of this clinical trial is to learn whether low-intensity focused ultrasound (LIFU), a non-invasive form of brain stimulation, can change brain activity and improve thinking and decision-making in adults with obsessive-compulsive disorder (OCD). The main questions it aims to answer are: Can active LIFU change activity in brain pathways involved in OCD? Can active LIFU improve the ability to control thoughts and actions? Researchers will compare active LIFU with sham LIFU to see whether active LIFU causes changes in brain activity and performance on behavioral tasks. Participants will: Complete questionnaires and behavioral tasks. Have magnetic resonance imaging (MRI) scans to measure brain activity and identify the area to receive LIFU. Receive both active and sham LIFU on separate visits. Have MRI scans and complete behavioral tasks after each LIFU session. Complete assessments of OCD symptoms, safety, and possible side effects.

Role of Theta Frequency Oscillations in Proactive and Reactive Control Processes in Youth With Attention Deficit Hyperactivity Disorder (ADHD) and Obsessive Compulsive Disorder (OCD)

Background: Attention deficit hyperactivity disorder (ADHD) is common in children. It can cause problems with attention and the ability to control actions and impulses. Obsessive compulsive disorder (OCD) is less common in children but not rare. It involves ongoing thoughts, urges, impulses, and repeated behaviors. Researchers want to study differences in brain activity between healthy children, those with ADHD, and those with OCD. Objective: To learn more about how the brain controls thinking and behavior. Eligibility: People aged 10 to 17 years with ADHD, OCD, or neither. Design: Participants will have 3 to 10 clinic visits in up to 1 year. Each visit will last 2 to 3 hours. Three visits are required: Behavioral. Participants will complete a computer task. Their mood, memory, attention, and thinking skills will be tested. EEG. Participants will undergo electroencephalography (EEG) to measure signals in their brain. Small electrodes will be placed on the scalp. A cap will be stretched over the head. Signals will be recorded while participants rest or do tasks on a computer. MRI. Participants will have a magnetic resonance imaging scan (MRI). They will lie on a table that rolls into a tube. The MRI will take pictures of their brain while they do tasks on a computer. Seven more visits are optional. These include 2 more EEG visits and 2 more MRI visits. Three will be magnetoencephalography (MEG) visits: MEG measures small magnetic field changes in the brain. A helmet with sensors will be placed on the head. Brain changes will be recorded while participants rest or do tasks on a computer.

OCD LIFU Target Engagement

The investigators will conduct a pilot study to evaluate the safety and feasibility of low-intensity focused ultrasound on obsessive-compulsive disorder (OCD) symptoms when delivered to subcortical brain targets. The investigators will use the ATTN201 device to deliver single sessions of unfocused and focused ultrasound to up to three brain targets over 4 study visits and assess the intervention through self-rated scales of OCD symptoms.

A Non-Interventional Pilot Study to Explore the Role of Gut Flora in Disease

This study seeks to correlate microbiome sequencing data with information provided by patients and their medical records.

Treatment Resistance in Psychiatric Disorders: the Search for Biological Markers Predictive of Response to Treatment

The disruption of immune system is a key candidate in the pathogenesis of psychiatric disorders, especially those resistant to traditional treatments. Involving complex processes within the brain and peripheral immune system, inflammation may lead to imbalance of neurotransmitter systems and synaptic plasticity and directly contribute to the psychiatric symptoms observed in conditions such as depression, bipolar disorder (BD) and schizophrenia (SCZ). Studies show that treatment-resistant depression (TRD) is associated with elevated levels of inflammatory markers in the blood, which are linked to a lower response to conventional antidepressants. Interventions that modulate this inflammatory response, such as immunomodulatory treatments or therapies targeting pro-inflammatory cytokines, have demonstrated beneficial effects by reducing symptoms and improving patients' quality of life. A thorough understanding of the links between inflammation and treatment resistance therefore paves the way for innovative therapeutic strategies. These approaches could transform current practices by offering more personalized and effective solutions for patients suffering from chronic and resistant psychiatric disorders.

Transcutaneous Electrical Acupoint Stimulation Combined With Exposure and Response Prevention in the Treatment of Patients With Obsessive-Compulsive Disorder: A Randomized Controlled Trial

Obsessive-compulsive disorder is a chronic and disabling mental disorder. Among them, 40-60% of obsessive-compulsive disorder patients do not respond to the current first-line drug treatment and/or psychological therapy. Traditional Chinese medicine treatment for obsessive-compulsive disorder has unique advantages. Acupuncture, as a traditional Chinese treatment technique, has been increasingly applied in the treatment of mental disorders such as insomnia, anxiety, and depression. Transcutaneous electrical acupoint stimulation (TEAS) can replace acupuncture. With equivalent effects, it can reduce pain and fear and is a non-invasive, safe, and time-saving physical intervention method. TEAS combined with exposure and response prevention therapy may have an additive effect in the treatment of obsessive-compulsive disorder. We will conduct a prospective randomized design to explore the integrated and optimized treatment plan of traditional Chinese and Western medicine for obsessive-compulsive disorder, improve the treatment efficiency, and reduce the proportion of chronic patients.

Bergen Four-Day Treatment (B4DT) for Obsessive-Compulsive Disorder

The aim of this study is to expand access to Bergen Four-Day Treatment (B4DT) in Finland and to integrate it into psychiatric care pathways at Tampere University Hospital (TAYS). A Bergen team has been established within TAYS Psychiatry and has been trained in collaboration with the B4DT team from HUS and the Norwegian developers. The objective of this study is to enhance understanding of the model's adaptability to the Finnish healthcare system, evaluate healthcare professionals' attitudes toward the intervention, and assess treatment outcomes. The aim is to recruit approximately 35 patients for the study. Patients will be recruited from a minimum of three groups (15 patients) and up to a maximum of six groups (35 patients). The criteria for admission to B4DT and for participation in the study are identical. The treatment and the study may include patients receiving specialized psychiatric care at Tampere University Hospital who have been diagnosed with obsessive-compulsive disorder and who experience significant impairment due to their symptoms. In addition, personnel from TAYS Psychiatry who recommend and refer patients for B4DT will be recruited for the study. The estimated number of participating staff members is approximately 30.

The Effects and Neural Mechanisms of Vitamin D and Iron-Immune Homeostasis on Inhibitory Control in Obsessive-Compulsive Disorder

This study is a randomized, open-labled, no-treatment-controlled clinical trial designed to investigate the effects of vitamin D and iron-immune homeostasis on inhibitory control and the underlying neural mechanisms in patients with obsessive-compulsive disorder (OCD). Participants will be patients with OCD who meet the study eligibility criteria. The study's primary aim is to compare changes in glutamate and related metabolite concentrations within the anterior cingulate-thalamic circuit, inhibitory control performance, peripheral immune markers, and clinical symptoms before and after treatment with calcitriol and iron polysaccharide complex. The study will also investigate the neural-circuit mechanisms underlying inhibitory control deficits in patients with OCD and their changes following the interventions. These objectives will be addressed using resting-state Magnetic Resonance Spectroscopy(MRS), inhibitory control tasks, peripheral blood immune-marker measurements, and clinical symptom assessments. The primary hypothesis is that inhibitory control deficits in patients with OCD are associated with dysregulated glutamatergic metabolism in the anterior cingulate-thalamic circuit. Vitamin D and iron supplementation are hypothesized to promote the balance of glutamate and related metabolites within this circuit, regulate immune homeostasis, and improve inhibitory control deficits in patients with OCD.

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.

Transcranial Direct Current Stimulation and Extinction in Obsessive Compulsive Disorder

Obsessive-compulsive disorder (OCD) is associated with substantial impairments in quality of life and is among the most disabling psychiatric disorders. Exposure therapy is among the first-line of treatments for obsessive-compulsive disorder (OCD) . Extinction learning is thought to be a core mechanism of therapeutic exposure. Fear and safety signal learning are traditionally associated with activity and connectivity within the canonical corticolimbic "fear circuit", which includes the amygdala, medial prefrontal cortex (mPFC), and hippocampus. Transcranial direct current stimulation (tDCS) is a neuromodulation technology that can augment brain plasticity, learning, and memory. The proposed study will test if obsessive-compulsive disorder (OCD) is associated with inhibitory safety learning deficits and if transcranial direct current stimulation (tDCS) normalizes functional connectivity and safety signal processing to recover extinction deficits in obsessive-compulsive disorder (OCD).

Neurophysiological Investigation of the Approach-avoidance Axis in OCD: Applications to Neuromodulation

We will recruit 10 patients with OCD meeting established criteria for surgical evaluation. Following informed consent and baseline evaluations, each will be implanted with permanent DBS SenSight leads and the Medtronic Percept RC IPG, which has on-device neural recording capability and rechargeability. We will collect a broad array of neurobehavioral data across two environments with complementary advantages: the clinic and the home. The first 2 Aims test our mechanistic hypothesis by studying the pattern of VS neural activity in the controlled environment of the lab/clinic during two complementary paradigms: one based on a psychophysical behavioral task, the other based on ERP, a therapeutic behavioral intervention. The third aim tests this hypothesis in an ambulatory, naturalistic setting with chronic neural on-device recordings paired with time resolved behavioral measures. We will investigate a possible common neural basis underlying approach and avoidance across these 3 paradigms. Subjects will participate in research at 7 critical timepoints during routine clinic visits (Fig. 4): before implant, 1 day before DBS activation, immediately after DBS activation, 2 weeks, 3 months, 6 months, and 12 months after DBS initiation. At these timepoints, patients will complete clinical assessments, perform the Probabilistic Approach Avoidance Task (PAAT), and conduct exposure trials under the guidance of a psychologist. The clinic offers the most controlled environment and provides opportunities for collecting high temporal resolution behavior synchronized to local field potential (LFP) recordings. These data will allow us to identify the degree of overlap in the time-resolved neural activity driving individual decisions to approach potential rewards or avoid potential aversive stimuli (Aim 1), and resist performing compulsions in order to achieve relief after OCD symptoms are triggered (Aim 2). At home, our goal is to investigate patient trajectories along the approach-avoidance axis as OCD symptoms improve (Aim 3). We will leverage passive, on device recordings that occur in the background of everyday life activities and synchronize these neural recordings with data collected via wearables, ecological assessments, and video diaries. Capturing neural and behavioral data in the home environment is essential for understanding the neural and behavioral changes that occur over longer timescales than individual clinical visits. The neurobehavioral biomarkers generated by this dataset will provide trackable readouts of clinical status that could inform therapeutic decision-making and enable data driven intervention.

Computer Game, Qualitative, and MEG/EEG Assessment of Serotonergic Psychedelics

This is an observational study which does NOT directly administer a psychedelic substance but rather recruits participants who are already participating in another clinical trial in which they may receive a serotonergic psychedelic. The goal of this observational study is to learn how the brain's information processing changes during and following administration of serotonergic psychedelics (psilocybin, N,N-Dimethyltryptamine/DMT, Lystergic Acid Diethylamide/LSD, etc.) for people with and without mental illness receiving serotonergic psychedelics through any clinical trial at Yale University. The main questions it aims to answer are: 1. Do serotonergic psychedelics cause the brain to rely on new information more than previously learned information while under the influence? What about 1 day, 5-14 days, and 4-6 weeks after use? 2. Do serotonergic psychedelics cause long-lasting side-effects in how people perceive (see, hear, feel, etc.) the world and how easily people change their beliefs? 3. How does the brain's electrical activity change after using serotonergic psychedelics? How does the balance between excitation and inhibition change while under their effect? 4. Can changes in how the brain uses information predict who will benefit from a psychedelic and who will have side effects from psychedelics? Researchers will compare with people given placebos to see what changes in brain processing are unique to serotonergic psychedelics. Participants will have the opportunity to do some combination of the following: 1. Online computer assessments consisting of games and questionnaires that probe how participants think. 2. Magnetoencephalography (MEG) or electroencephalography (EEG) with eyes closed and with repeated clicks, images, or sensations delivered. 3. A magnetic resonance imaging (MRI) scan. 4. Semi-structured qualitative interviews about their experience after taking a serotonergic psychedelic recorded via Zoom.

Connectomic Deep Brain Stimulation for Obsessive Compulsive Disorder

Deep brain stimulation (DBS) is an effective treatment for people suffering from severe obsessive-compulsive disorder (OCD) whose symptoms have failed to improve after years and multiple methods of intervention. An effective DBS target for OCD is the anterior limb of the internal capsule (ALIC) brain region. On average 60% of all OCD patients have a clinically significant response to ALIC DBS. However, ALIC DBS may become even more effective with the ability to predict which specific ALIC connections in the brain need to be stimulated for each individual OCD patient. This study therefore investigates personalized stimulation to the ALIC that allows for precise modulation of brain circuits associated with individual OCD symptoms. The study aims to specify the ideal anatomical target for ALIC DBS for maximum therapeutic benefit in each patient.

Non-Coding RNAs Gene Expression in Psychiatric Disorders

This study aims to investigate whether specific non-coding RNAs, molecules involved in the regulation of gene expression, are altered in individuals with psychiatric disorders such as schizophrenia, bipolar disorder, major depressive disorder, panic disorder, and obsessive-compulsive disorder. Researchers will compare the expression levels of these molecules in patients who are drug-naïve or have been free from psychiatric treatment for at least six months with those observed in healthy volunteers. The study will also evaluate whether the expression of these non-coding RNAs changes after approximately five months of standard psychiatric treatment. Blood samples collected during routine clinical care will be used to measure the expression levels of selected non-coding RNAs using reverse transcription quantitative polymerase chain reaction (RT-qPCR), a laboratory technique used to assess gene expression. This is an observational study and does not assign specific treatments. All therapies will be prescribed according to standard clinical practice. The main objective is to determine whether alterations in non-coding RNA expression may serve as biological markers of psychiatric disorders and whether these markers may help monitor treatment-related changes over time. The findings may contribute to a better understanding of the biological mechanisms underlying major psychiatric disorders and support the future development of more accurate diagnostic and therapeutic approaches.

ERP to Improve Functioning in Veterans With OCD

Obsessive compulsive disorder (OCD) is a debilitating psychiatric illness impacting work, social, and family functioning. Exposure and Response Prevention (ERP) is the sole evidence-based psychotherapy for OCD; however, no randomized controlled trials (RCTs) have examined the effectiveness of ERP among Veterans or individuals with both OCD and posttraumatic stress disorder (PTSD). This 4-year Hybrid Type I trial will compare outcomes of ERP to those of a control condition among Veterans with OCD. Primary and secondary aims will examine whether Veterans' functioning, quality of life, and OCD symptoms differ between the ERP and control in the full sample of Veterans with OCD, and in the half of the sample with both OCD and PTSD. The tertiary aim is to conduct a mixed-methods formative evaluation of the implementation potential of ERP in VA mental health settings.

A Lifestyle Intervention to Reduce Cardiometabolic Risk Factors in Individuals With Obsessive-compulsive Disorder

The overall aim of this study is to evaluate the efficacy and cost-effectiveness of a lifestyle intervention to improve lifestyle habits and reduce cardiometabolic risk factors in individuals with obsessive-compulsive disorder (OCD).

iCBT for Adolescents Obsessive-compulsive Dissorder

The goal of the study is to assess the feasibility, acceptability, and potential effects of therapist-guided internet-delivered cognitive-behavior therapy (iCBT) for adolescent obsessive-compulsive disorder, using a recently developed digital platform.

Priming CBT With rTMS for OCD

Cognitive behavioural therapy (CBT), incorporating exposure/response prevention (ERP) and cognitive therapy, is considered the gold-standard first-line treatment for obsessive-compulsive disorder (OCD). Because CBT is a psychological treatment that aims to change patterns of thinking and behaving, it may be that improvement in cognitive functioning before treatment starts could lead CBT to be even more effective. One area of research that has shown potential benefit for OCD sufferers is rTMS. rTMS is a non-invasive procedure that uses pulses of energy to stimulate regions of the brain. Brief treatment with rTMS has shown to improve attention, memory, and other aspects of cognitive functioning that may facilitate learning in CBT. The proposed study aims to provide a pilot test of the clinical effectiveness of adding brief rTMS prior to completing CBT for OCD. If rTMS can demonstrate enhancement of cognitive functioning, which in turn, can improve treatment response to CBT, then the findings could easily be translated into routine clinical care.

Stepped Care Treatment for Anxiety Resilience

Childhood anxiety disorders (CAD) are common and impairing. Family based cognitive behavioral therapy (CBT) is efficacious in treating CAD. Yet, many children do not receive care due to barriers such as limited provider availably, high treatment costs, and constrained family resources (e.g., time). To combat these barriers, other treatment methods have been developed. The stepped care treatment models maximize resources by providing low-intensity, low-cost interventions as a first time treatment, while stepping up care for those needing more intensive treatment. Specifically, a stepped care model for CAD that begins with a parent-focus intervention has great promise to deliver efficacious and cost-effective treatment without having to engage the child. While stepped care approaches show promise in treating CAD with comparable efficacy to standard CBT, there remains a large research-to-practice gap. The stepped care model for CAD that begins with a parent-focused intervention has yet been explored, and very little is known about intervention mediators that explain mechanisms of change. This research is being done to improve the reach and quality of services using a stepped care model, offering an affordable and practical solution to the widespread gap in youth mental health care.

Assessments of Obsessive-compulsive Symptoms in Patients With Substances Use Disorder

This observational, cross-sectional case-control study evaluates obsessive-compulsive symptoms among adults with substance use disorder compared with a demographically similar control group without substance use disorder. Patients aged 18-50 years attending the addiction management inpatient and outpatient services at Assiut University Hospital, and healthy controls recruited from relatives, friends, and hospital staff, will complete structured clinical interviews, the Yale-Brown Obsessive-Compulsive Scale, and other standardized scales for psychiatric symptoms, cognition, and quality of life. The main objective is to estimate the prevalence and severity of obsessive-compulsive symptoms in substance use disorder and examine their associations with sociodemographic and clinical factors, addiction severity, and quality of life in the recovery stage.