Clinical Research Directory

TMS + Exposure Therapy for Pediatric OCD

The goal of this clinical trial is to compare different forms of transcranial magnetic stimulation (TMS) for improving the outcomes of Exposure with Response Prevention (ERP) in youth and young adults with Obsessive-Compulsive Disorder (OCD). Researchers will compare three groups: ERP with one of two different active ("real") forms of TMS vs. ERP with sham ("fake") TMS. The main questions this study aims to answer are: 1) whether TMS normalizes functioning in brain circuits that contribute to compulsive behavior, and 2) whether TMS reduces compulsions during ERP. Participants will: * Complete clinical interviews, questionnaires, and computerized tasks * Complete two MRIs (brain scans) * Receive daily TMS followed by ERP for two weeks (10 sessions)

Anxiety Skills Study

The purposes of this study are: (1) to identify baseline predictors of relative success in cognitive, behavioral, and mindfulness-based treatments for anxiety, (2) explore who benefits from a brief, video-based skill training compared to receiving 4 sessions of therapy, and (3) to evaluate how durable these effects are over 1 year.

Understanding How Ketamine Brings About Rapid Improvement in OCD

The purpose of this study is to understand how ketamine brings about rapid improvement in Obsessive-Compulsive Disorder (OCD) symptoms.

ERP Plus Improv Group Therapy for OCD (IMPROVE Study)

The goal of this study is to pilot test a novel group therapy intervention for adults with OCD.

Pilot Study of RR-HNK in OCD

The purpose of this study is to understand how RR-HNK works in the brain to bring about a reduction in OCD symptoms.

Neural Mechanisms of Response Inhibition Training for OCRD

The impaired ability to suppress an inappropriate but pre-potent response (response inhibition; RI) characterizes several debilitating clinical problems, including obsessive-compulsive and related disorders (OCRD) such as obsessive-compulsive disorder, trichotillomania, and skin picking disorder. There is a critical need to develop an effective and durable treatment for OCRDs with demonstrable evidence for improving impaired RI. The purpose of our project is to examine the impact of a novel computerized intervention, response inhibition training (RIT), on neural indices of RI, and examine the mechanistic link between engagement of the neural RI targets and change in OCRD symptoms. To this end, this project will conduct a randomized clinical trial for individuals with OCD, trichotillomania, and/or skin picking disorders. Participants will be randomly assigned to 8 to 16 sessions of computerized RIT or a computerized placebo training. Various clinical, behavioral, and brain-imaging data will be acquired to evaluate the training effects at baseline, post-training, and 1-month follow-up periods.

Precision Brain Mapping to Predict and Track Response to Exposure and Response Prevention Therapy in Youth With Obsessive-Compulsive Disorder

The goal of this clinical trial is to learn whether brain scan results can help predict and track changes in obsessive-compulsive disorder, or OCD, symptoms in children and teens ages 10 to 17 who receive Exposure and Response Prevention therapy, also called ERP. ERP is a type of therapy in which participants practice facing OCD-related fears while resisting rituals or compulsions. The main question this study aims to answer is: Can each participant's pattern of brain connections, measured with functional MRI brain scans, help predict and track weekly changes in OCD symptoms during and after a 14-week course of ERP, including during planned monthly booster sessions and additional booster sessions offered if symptoms worsen? All participants will receive ERP. There is no placebo and no comparison group. Participants will: * Complete screening, consent or assent, interviews, questionnaires, and MRI safety checks * Receive 14 weekly ERP sessions * Complete OCD symptom assessments and functional MRI brain scans before, during, and after ERP * Receive planned monthly ERP booster sessions after the 14 weekly sessions * Receive additional brief ERP booster sessions if OCD symptoms worsen during follow-up * Take part for up to about 62 weeks

CBT Augmentation to Promote Medication Discontinuation in Pediatric OCD

The purpose of this study is to examine whether youth with OCD who benefit from CBT augmentation to SRI can discontinue their medication without relapse over 24 weeks.

Pathogenesis of Pediatric Obsessive-compulsive Disorder: Based on the Microbiota-gut-brain Axis

This study aims to investigate the characteristics of the microbiota-gut-brain axis in pediatric patients with obsessive-compulsive disorder (OCD) through performing an integrated analysis of gut microbiota, serum metabolomics, neuroimaging and electroencephalography (EEG), conducted before and after treatment with selective serotonin reuptake inhibitors (SSRIs). The results will be compared with those of pediatric OCD paitents comorbid with tic disorder (TD) and healthy controls. The findings are expected to further elucidate the potential pathogenesis of OCD, providing a theoretical basis for identifying novel clinical intervention targets and optimizing treatment strategies.

Brain Recordings in Patients Undergoing Deep Brain Stimulation (DBS) for Severe Obsessive-Compulsive Disorder (OCD)

Obsessive-compulsive disorder effects approximately 2-3% of the population. The only established first-line treatments for OCD are cognitive-behavioral therapy (CBT) with exposure/response prevention and serotonin reuptake inhibitor medications (SRIs). Approximately 30-40% of patients fail to respond to either modality and few patients experience complete symptom resolution. Up to 25% of patients have difficulty tolerating CBT, and the risk of relapse after therapies remains significant. Symptoms of OCD include unwanted, distressing thoughts and rituals such as excessive washing of hands or other body parts, rechecking things such as locks or switches because of obsessional doubt, and avoidance of anxiety-provoking situations. In some cases, compulsions can consume several hours per day and in the most extreme cases can involve most of the patient's waking hours (e.g. washing hands hundreds of times per day, 18-hour showers). Medical complications may result from repeated washing or other repetitive behaviors. Significant social and occupational impairment can result from this disorder and some patients are housebound or even bed-ridden. Effective evidence-based treatments include behavior therapy and certain medications. Despite these therapies, a significant number of patients are treatment resistant and suffer persistent, debilitating symptoms. In severe cases, neurosurgical intervention is sometimes performed to alleviate symptoms. A common surgical option is deep brain stimulation (DBS), a procedure that involves placing two electrodes in a specific region in the brain and connecting them to a pacemaker-like device implanted under the skin in the upper chest. The clinician adjusts the stimulation parameters on the device to find the settings that best relieve symptoms. One of the challenges of treating a psychiatric disorder is the absence of reliable and valid biomarkers for diagnosing and objectively monitoring treatment outcomes. There is also problem of heterogeneity, which introduces additional barriers to predicting who will respond best to a particular treatment. A better understanding of the dysfunction in key brain circuits underlying OCD symptomatology will allow us to improve outcomes with DBS. The pathophysiology of OCD is associated with dysfunction in prefrontal cortico-basal ganglia circuits. The electrodes of the DBS system are placed at a critical hub within this circuit. This target is called the ventral capsule/ventral striatum (VC/VS). DBS targeting the VC/VS is approved for the treatment of severe OCD under an FDA Humanitarian Device Exemption (HDE). In this project, the investigators will recruit patients treated with DBS for OCD under the standard clinical (HDE) pathway. The FDA/HDE-approved device for these procedures is the Medtronic Percept DBS system. The Percept implanted pulse generator (IPG; pacemaker-like device mentioned above that delivers stimulation) has the ability to not only stimulate, but also record electrical activity measured from the brain electrodes, store the recordings in memory, and wirelessly transmit them to the clinician. The investigators will ask consenting patients to perform and transmit these recordings to the investigators for analysis. The investigators hope that these recordings will help them understand the relationship between electrical network activity in the brain and patient symptoms. A closer understanding of this relationship may eventually enable the investigators to make better informed programming adjustments and therefore achieve better symptom control. The main objective is to obtain recordings from the VC/VS, a key network hub in OCD, in patients already implanted with a DBS system for severe OCD. The Investigators will use these recordings to better understand the relationship between brain activity and OCD symptoms, with the hope that this understanding will lead to more effective utilization of DBS therapy to treat severe OCD.

Epidiolex in Obsessive Compulsive Disorder and Related Disorders

The primary objective of the proposed study is to evaluate the safety and efficacy of Epidiolex (cannabidiol) in adults with obsessive compulsive and related disorders (OCRDs). Subjects will be treated in an open-label fashion with Epidiolex for two weeks.

Feasibility, Clinical Effects, and Safety of Psilocybin-assisted Psychotherapy for Treatment-resistant OCD

Psilocybin, the chemical component of "magic mushrooms", has been administered with psychotherapy in several randomized clinical trials (RCTs) showing large and sustained antidepressant effects. There is interest to see if similar effects may be provided in those with obsessive compulsive disorder (OCD). The purpose of this study is to evaluate the safety, feasibility, and clinical effects of psilocybin administration in those with OCD. Ten participants with treatment-resistant OCD will receive two doses of 25mg of psilocybin under supportive conditions, two weeks apart. The investigators hypothesize that two sessions of psilocybin 25mg administered under supportive conditions to participants with treatment-resistant OCD will lead to significant reductions in OCD symptoms.

Psilocybin Whole Mushroom for the Treatment of Obsessive-compulsive Disorder.

The study tries to improve our treatments for people who have obsessive-compulsive disorder (OCD) by testing psilocybin, a mind altering drug that changes activity in brain areas involved in OCD. 30 patients with moderate or more severe OCD who are not taking mind altering medications or street drugs will participate in a 12 week study. Participants will be assigned (by luck of the draw) to take a low, medium, or high dose whole psilocybin mushroom contained in three chocolate pieces, prepared for this study by the Scottsdale Research Institute.

Digital Mindfulness-Based Therapy for Obsessive-Compulsive Disorder

This randomized controlled trial aims to evaluate the effects of digital mindfulness-based therapy in people with obsessive-compulsive disorder and to explore its possible psychological and neurophysiological mechanisms. A total of 150 participants with a primary diagnosis of obsessive-compulsive disorder will be randomly assigned in a 1:1:1 ratio to one of three groups: digital mindfulness-based therapy, routine pharmacological treatment, or digital mindfulness-based therapy combined with routine pharmacological treatment. The digital mindfulness-based therapy program will last for 6 weeks and will be delivered through a mobile mini-program using structured video and audio lessons, guided mindfulness practices, supervised weekly learning, and home practice. Participants in the pharmacological treatment group will receive routine pharmacological treatment for obsessive-compulsive disorder, and participants in the combined group will receive both interventions. Changes in obsessive-compulsive symptoms, mindfulness, emotional symptoms, and other psychological outcomes will be assessed during treatment and follow-up. Heart rate variability will be assessed at baseline and weekly during the 6-week intervention. Electroencephalography will be assessed at baseline, at the end of the 6-week intervention, and at the 3-month and 6-month follow-up assessments to explore neurophysiological changes associated with treatment.

Search for Novel Transcranial Magnetic Stimulation (TMS) Targets for Mental Illness

Participants will receive Transcranial Magnetic Stimulation (TMS) at a random location in the left prefrontal cortex, excluding sites that are potentially unsafe. Extensive behavioral testing will be conducted to determine which behaviors are modulated by stimulating which circuits.

Using Personalized Assessments in the Treatment of Childhood OCD

The primary purpose of this study is to learn whether personalized assessment of obsessive-compulsive disorder (OCD) symptoms in childhood OCD using mobile health technology are feasible and acceptable for youth and parents. The investigators will also examine whether personalized cognitive-behavioral therapy (CBT) that is informed by personalized OCD assessments yields better clinical outcomes when compared to standard CBT for youth with OCD

Study on the Efficacy Mechanism of Natural Psychotherapy for Neurosis

explore objective indicators of the efficacy of natural psychotherapy in the treatment of disorders such as obsessive-compulsive disorder

Locating Biomarkers in OCD Through Behavioral Tasks

Subjects that have a diagnosis of OCD will participate in a clinical interview and cognitive tasks, during which they will be exposed to their individual OC stressors or will be asked to make decisions related to information value and quantity while measuring neural activity and filming facial reactions. This will assist investigators to look for biomarkers of that change. This study offers a unique opportunity to develop biomarkers for key domains of OCD, and other neuropsychiatric disorders, that are grounded in brain neurocircuitry at the individual-patient level. Subjects will participate in a clinical interview (Day 1), and then tasks+EEG (Day 2). Day 1 will be 4 hours or less, and Day 2 will be 2.5 hours or less.

Mechanisms of Exposure Therapy for OCD

Exposure therapy is the most effective treatment available for obsessive compulsive disorder, yet up to 50% of patients do not recover because the mechanisms underlying successful response are poorly understood, leading to significant variability in how clinicians conduct exposure therapy. The main purpose of this study is to determine which target mechanisms are most critical to engage in real-world exposure sessions to produce good treatment outcomes. Adult participants (N = 400) with Obsessive Compulsive Disorder (OCD) receiving exposure therapy from two sites (McLean Hospital, San Diego State University) across the continuum of care (outpatient, partial hospital, residential) will complete baseline clinical and demographic measures as well as weekly symptom reports. The project will measure exposure mechanisms across three levels of analysis (self-report, observer-rated behavior, physiology) during each exposure session. Mechanisms assessed will include a broad range of variables based on both habituation and inhibitory learning models of exposure. Self-report and observer-rated mechanisms will be measured with the Exposure Feedback Form, created and piloted by the study team. Physiological mechanisms will include skin conductance response, heart rate, and heart rate variability measured with a wristwatch. The current study will determine (1) which exposure mechanisms lead to favorable clinical outcomes, and (2) what makes a good exposure for whom. Results of this study have the potential to improve personalized care for the many patients who do not remit following exposure therapy for OCD.

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?"

A Clinical Trial of Tolcapone in Obsessive Compulsive Disorder

The primary aim of the present study is to examine the efficacy and safety of tolcapone in adults with moderate to severe OCD.

Valbenazine in Obsessive Compulsive Disorder

The primary aim of the study is to examine the efficacy and safety of valbenazine in adults with moderate to severe obsessive-compulsive disorder (OCD).

Project EMPOWER-OCD

This research study aims to adapt and evaluate the acceptability and effectiveness of Project EMPOWER-OCD for socioeconomically diverse caregivers of patients with OCD. Designed to reduce obstacles (e.g. months long time commitment, high cost, transportation) to treatment that caregivers may be particularly prone to, project EMPOWER-OCD will provide targeted intervention of accommodation - a well-established, potentially modifiable risk factor for child anxiety, OCD, and its related disorders - in a single, self-guided session via an online format.

Personalized DBS for OCD Guided by Stereoencephalography Mapping

This is a double-blinded, randomized, crossover study design for SEEG-guided 4-lead DBS for treatment-refractory OCD, followed by open label stimulation for an additional 6 months. The study will be conducted in 3 stages: Stage 1 will consist of SEEG brain mapping and optimization of stimulation parameters. Stage 2 will consist of 4-lead DBS surgery with bilateral IPGs and further optimization of stimulation parameters. Stage 3 will be randomized, crossover treatment, followed by open label treatment.