Clinical Research Directory

A Study to Assess the Efficacy and Safety of ITI-1284 in the Treatment of Psychosis Associated With Alzheimer's Disease

This is a multicenter, randomized, double-blind, parallel-group, placebo-controlled, flexible-dose study evaluating the efficacy, safety, and tolerability of ITI-1284 compared with placebo in the treatment of psychosis in patients with AD.

Sensory Profile and Early Clinical Signs of Calm Room Users

This descriptive study aims primarily to characterize the sensory profile of patients in a closed psychiatric hospital unit who use a calming room. The main questions it aims to answer are : * Could sensory information processing disorders be the cause of distress and tension in these patients? * Could users of the calming room present extreme sensory processing profiles, characterized by either hypersensitivity or hyposensitivity ? Participants will answer a survey to determine their the sensory profile. Participants can already use the calming room as part of their regular medical care and they will answer surveys before and after each use.

Assessment and Treatment for Chronic Pain in Veterans With Serious Mental Illness

Chronic pain has a highly negative impact on Veterans, especially those with serious mental illness (SMI). Chronic pain leads to poorer mental health and physical functioning, and represents a critical obstacle to rehabilitation and recovery. Despite known high prevalence rates of chronic pain in SMI populations, there is little research to: a) evaluate nonpharmacological pain management strategies in this population, and b) examine directional relations between chronic pain and SMI symptoms. This study aims to address research and clinical gaps by: a) testing the feasibility and acceptability of Cognitive Behavioral Therapy for Chronic Pain (CBT-CP) - a VA evidence-based psychotherapy for chronic pain - in Veterans with SMI, and b) better assessing the complex relation between chronic pain and psychiatric symptoms and their impact on functioning. Results from this study will inform us as to whether CBT-CP is feasible to implement, acceptable to Veterans with SMI, and worth examining in its standard or in an optimized form in a larger clinical trial.

Theta-Burst Transcranial Magnetic Stimulation for Treatment-Resistant Auditory Hallucinations

The goal of this clinical trial is to learn whether theta-burst transcranial magnetic stimulation (TBS), a non-invasive brain stimulation technique, can help reduce persistent auditory verbal hallucinations (hearing voices) in adults with psychotic disorders who have not responded adequately to antipsychotic medications. The main questions it aims to answer are: * Does theta-burst stimulation reduce the severity of auditory verbal hallucinations? * Does theta-burst stimulation improve other psychiatric symptoms, including depressive symptoms and insight into illness? * How well do participants tolerate this treatment, and what side effects do they experience? All participants will receive active theta-burst stimulation. There is no placebo or comparison group. Participants will: * Complete an initial assessment of their mental health, symptoms, and medical history. * Receive 20 brain stimulation sessions over two consecutive weeks, with two sessions per day on weekdays. * Complete follow-up assessments approximately one week and one month after treatment to evaluate changes in symptoms and overall functioning. * Report any side effects experienced during treatment and follow-up.

Supporting Patients by Family Education in Psychotic Illness: A Prospective Cohort Study

Background: A lack of education, resources, and support for family carers of young adults with psychotic illnesses leaves them ill-equipped to support their loved one. Although family support groups exist, few groups offer evidence-based, skills-focused, psychoeducation taught by certified professionals and provided on a public-health level. By equipping families with skills and knowledge, public healthcare harnesses a powerful ally to maintain community stabilization. Aims: The primary study goal is to implement a psychoeducation intervention for family carers supporting young adults with psychosis to reduce family burden and foster community stabilization of service users. Methods: A longitudinal pre-post design will be used to assess the long-term effectiveness of the psychoeducation intervention for family carers supporting a young adult with psychosis on service utilization and functional indexes. Nine expert-reviewed, and family peer-informed psychoeducation modules are administered in 2-hour sessions over 9 weeks to family carers. Conclusion: Presenting the novel approach of an expert-reviewed, peer-informed psychoeducation intervention for family carers, with a focus on knowledge and skill development, the researchers contribute to literature and best practice in patient and family-centered care.

Hormonal and Inflammatory Biomarkers and Response to Cognitive Remediation in Recent-onset Psychosis

This study aims to explore whether hormones or inflammatory markers are associated with cognitive changes following cognitive remediation therapy (CRT) in people with a recent-onset psychotic disorder. The following biomarkers for treatment response will be considered: hormones related to the hypothalamic-pituitary-adrenal (HPA) axis (plasma cortisol, cortisol awakening response, diurnal cortisol slope, salivary cortisol at assessment), free thyroxine (F-T4), prolactin, or inflammatory markers. This study was designed as a pilot clinical trial in order to know the feasibility of the intervention and to calculate the effect sizes of different hormonal and inflammatory variables on cognition. This approach would allow the design of future larger clinical trials to test specific hypotheses generated with this study.

Reducing Weight and Diabetes Risk in an Underserved Population (STRIDE)

The purpose of this study is to examine the effectiveness of a lifestyle intervention designed to reduce weight and diabetes risk in a population of individuals with mental illness who are also taking antipsychotic medications. We will examine the effectiveness of the intervention in 1. reducing weight and Body Mass Index; 2. reducing fasting insulin levels and increasing insulin sensitivity; and 3. reducing total cholesterol and LDL cholesterol.

Stratification and Treatment in Early Psychosis Study - ENHANCE

The purpose of this study is: * To investigate whether the response to antipsychotic treatment can be enhanced by adding cannabidiol (CBD) to the existing treatment, compared to placebo, in participants with a first episode of psychosis, who have had a suboptimal or no response to their first antipsychotic treatment. * To confirm the safety of CBD in people with psychosis. The study is a randomized, double-blind, placebo-controlled, multi-centre, clinical trial. Individuals with a diagnosis of first-episode psychosis, who have had a suboptimal or no response to their first antipsychotic treatment will be recruited. These participants are randomised to treatment with CBD oral solution 500mg twice daily, or a matching placebo for 6 weeks, as an adjunct to their existing antipsychotic treatment. By using a battery of clinical outcome assessments, the trial will also assess several biomarkers to determine if they can be used to predict clinical outcomes and response to treatment with CBD. Biomarkers are being assessed as an exploratory outcome measure. Participants will be invited to provide blood and stool samples, and may be asked to complete neuroimaging assessments at certain eligible sites.

A Closed Unit Incorporating Soteria Elements Versus a Conventional Closed Psychiatric Ward

This prospective study compares two models of inpatient psychiatric care for adults experiencing an acute psychotic episode of moderate to severe intensity that requires admission to a closed psychiatric setting. Participants may have a history of previous psychiatric hospitalizations. After informed consent and completion of all baseline assessments, eligible participants are randomly assigned to either a small closed unit incorporating Soteria elements or a conventional closed psychiatric ward at the Jerusalem Mental Health Center. Treatment allocation remains concealed during the baseline assessment, so that participants and researchers completing the initial assessments do not know the participant's future treatment setting. Because the study is conducted under real-world emergency psychiatric conditions, random allocation may not always be feasible because of clinical urgency, bed availability, administrative constraints, or difficulty obtaining consent and completing study procedures during an acute psychotic episode. When randomization cannot be implemented, eligible participants may still be enrolled and their method of allocation will be documented. The closed unit incorporating Soteria elements provides care in a smaller setting of approximately 10 patients and emphasizes a calm and less institutional environment, supportive therapeutic relationships, shared decision-making whenever possible, personal autonomy, reduced reliance on coercive practices, and careful optimization of medication. The conventional closed ward provides standard acute inpatient psychiatric care in a larger ward setting. The primary aims are to compare the relationship between antipsychotic medication dosage and improvement in psychotic symptoms, as well as therapeutic alliance and satisfaction with care, between the two treatment settings. Secondary outcomes include personal recovery, sense of dignity, internalized stigma, adverse events and coercive interventions during hospitalization, length of stay, and other clinical and post-discharge outcomes. Psychiatric readmission within one year after discharge is included as a primary outcome. Baseline assessments are completed before treatment allocation is disclosed. At discharge and follow-up, full blinding is not always feasible because participants may reveal their treatment setting; however, outcome assessments will be conducted with partial blinding whenever possible, and the success of blinding will be documented. The primary statistical analysis will focus on participants who were randomly assigned. Additional analyses will compare randomly and non-randomly allocated participants and will include all eligible participants using statistical adjustment for relevant baseline differences and potential confounding. Sensitivity analyses restricted to the randomized sample will be conducted to assess the robustness of the findings.

Investigating the Neural Correlates of Cognitive Function in Psychosis Patients and Non-Psychiatric Controls With Cannabis Use

Cognitive impairment is well established in people with psychosis and is associated with cannabis use. The current study will investigate the neurobiological basis of cognitive change associated with 28-days of cannabis abstinence in people with psychosis and non-psychiatric controls with cannabis use. Participants will be randomized to a cannabis abstinent group or a non-abstinent control group and will undergo magnetic resonance imaging at baseline and following 28-days of abstinence. This study will help characterize the neuropathophysiological processes underlying cognitive dysfunction associated with cannabis use and its recovery which may guide the development of novel interventions for problematic cannabis use.

Accelerated Neuromodulation Therapy and Neurocomputational Biomarkers in Individuals at Clinical High Risk for Psychosis

The goal of this study is to learn whether an accelerated form of neuromodulation therapy is safe, feasible, and well tolerated in young people at clinical high risk for psychosis (CHR-P), and whether it is associated with changes in candidate biomarkers of treatment response. Participants will be randomly assigned to receive either active accelerated intermittent theta burst stimulation (iTBS) or sham stimulation to the left dorsolateral prefrontal cortex, delivered over five consecutive days. The study will look at whether this accelerated treatment approach is safe and feasible for people at clinical high risk for psychosis, whether depressive symptoms improve after treatment, and whether computerized behavioural tasks and passive digital monitoring (wearables, smartphone apps, and speech analysis) can detect treatment-related changes that may serve as biomarkers for future, larger trials. Participants will complete clinical interviews and questionnaires, a cognitive battery, and computerized behavioral tasks; wear a Fitbit and use smartphone applications for at least two weeks before and throughout treatment; receive neuromodulation therapy or sham stimulation over five consecutive days; and attend follow-up visits at 1 week, 1 month, and 3 months after treatment.

Face Your Fears: Cognitive Behavioural Virtual Reality Therapy for "Paranoia".

The study is a randomised, assessor-blinded parallel-groups superiority clinical trial fulfilling the CONSORT criteria for non-pharmacological treatment. A total of 256 patients will be allocated to either Cognitive Behavioural Virtual Reality Therapy plus treatment as usual, versus traditional CBT for psychosis plus treatment as usual. All participants will be assessed at baseline and 3- and 9 months post baseline. A stratified block-randomisation with concealed randomisation sequence will be conducted. Independent assessors blinded to the treatment will evaluate outcome. Analysis of outcome will be carried out with the intention to treat principles.

Improving Heart and Metabolic Health in People With Severe Mental Illness Through a Long-term Clinical Trial

Background Cardiometabolic conditions-including cardiovascular disease, type 2 diabetes, and obesity-are highly prevalent among individuals with psychotic disorders. These conditions contribute substantially to reduced life expectancy, diminished quality of life, and increased societal and economic burdens. Thus, effective, individualized interventions are urgently needed. Outpatient psychiatric clinics offer an ideal setting for such efforts owing to regular patient contact and access to multidisciplinary care. We have developed a comprehensive, clinically integrated trial aimed at improving cardiometabolic health, promoting healthier lifestyles, and enhancing quality of life for individuals with psychotic disorders receiving care in the Greater Gothenburg region. Methods LAGOM is a multicenter, naturalistic, quasi-experimental case-control trial conducted across six geographically separate outpatient psychosis clinics within the Department of Psychotic Disorders at Sahlgrenska University Hospital, a multi-site university hospital in the Greater Gothenburg region. A total of 650 adults with psychotic disorders will be recruited from these clinics. Two clinics will implement the LAGOM intervention, whereas four will serve as control sites delivering usual care. The intervention is embedded within routine psychiatric care and grounded in behavioral science. It includes comprehensive cardiometabolic risk assessments, two visual motivational tools (QRISK3 and a body composition analyzer), personalized follow-up plans, risk-oriented referrals to primary care, and structured education for patients, relatives, and staff. The intervention is designed to be scalable, sustainable, and tailored to individual patient needs. Discussion If proven superior to usual care, this pragmatic, multicomponent intervention-delivered within routine psychiatric care-could improve cardiometabolic health and quality of life for individuals with psychotic disorders. Embedding the intervention within existing clinical structures enhances its scalability and feasibility and, if effective, could serve as a model for wider implementation.

The Combination of Pharmacotherapy and Cognitive Behavioral Psychotherapy Under the Recovery Perspective.

The combination of pharmacotherapy and individual cognitive behavioral therapy in a private practice.

A Novel Peer-Delivered Recovery-Focused Suicide Prevention Intervention for Veterans With Serious Mental Illness

Suicide is a major public health concern, particularly among Veterans with serious mental illness (SMI, i.e., psychotic disorders or bipolar disorders). Wellness Recovery Action Plan (WRAP) is a well-established evidence-based practice for those with SMI that centers on identifying warning signs of mental illness, developing wellness tools for functional independence, planning for day-to-day effective living within one's community, and building an action plan to create a valued life worth living. This proposed study will refine and pilot SUicide Prevention by Peers Offering Recovery Tactics (SUPPORT), a novel integrated recovery program that is an adaptation of peer-delivered WRAP for Veterans with SMI. In SUPPORT, a Peer Specialist leads a Veteran at increased risk for suicide through recovery planning that is tailored to the Veteran's suicidal experiences with cognitive learning strategies to enhance safety plan recall and improve functioning.

Efficacy of an Online-Based Self-Help Intervention for Auditory Hallucinations in Persons With Psychotic Disorders

The proposed clinical trial aims to examine the efficacy of an online-based self-help intervention for auditory hallucinations in persons with psychotic disorders. The intervention is primarily based on Metacognitive Training (MKT) and Mindfulness-Based Group Therapy (MBGT). The investigators will utilize a mixed-method study design within a randomized controlled trial. The intervention group will be compared with a waitlist-control group (WL-TAU). Both study conditions are allowed to continue standard scheduled treatment. The aim is to analyze the efficacy of and the subjective satisfaction with the intervention, based on self-report assessments evaluated from baseline (T0) to post-intervention after 6 weeks (T1).

Computer-assisted Risk Evaluation in the Early Detection of Psychotic Disorders

Multicenter randomized controlled trial (RCT) with artificial intelligence (AI)-staged early diagnostics and risk-adapted treatment (RAB) as interventional treatment arm and treatment-as-usual (TAU) as control treatment arm for patients with an increased clinical risk for psychosis.

Brain and Oculometric Markers of Emotional Facial Expression Recognition Deficits

Disorders in the recognition of emotional facial expressions are part of the social cognition disorders described in several diseases. They are notably present in a quasi-systematic way in diseases associated with socio-emotional behavior disorders, such as schizophrenia and autism. They are also found in some genetic syndromes with atypical neurodevelopment. In previous studies, the investigators adopted the FPVS-EEG approach to investigate facial emotion discrimination abilities in typical and atypical developing populations. the investigatorshave shown that, in typical adults, the neural response to facial expressions emerges as emotional intensity parametrically increases. A time-domain analysis revealed three components, with the first two increasing linearly with expressive intensity, and the third (beyond 300 ms) showing categorical sensitivity to increasing expressive intensity. The investigators have already successfully extended this approach to the investigation of patients, such as those with 22q11.2 syndrome. The brain response to facial expression was reduced by approximately 36% in these patients, revealing impaired visual coding of emotional facial signals. In this study, response amplitude was associated with positive symptom severity, indicating a potential endophenotype for psychosis risk. Here, the investigators study the implementation of high-level processes and the top-down effect it should have on the response of occipitotemporal regions to identify altered brain markers in schizophrenic patients, but also in other populations with expression recognition deficits (autistic, 22q11.2, in particular). The implementation of compensatory strategies that should result in an increased exploration of the lower part of the face at the oculometric level will also be studied.

Development of a Transdiagnostic Intervention for Adolescents at Risk for Serious Mental Illness

This research study aims to develop a brief group-based treatment called Resilience Training for Teens, then to test how well it protects high school students with mild symptoms of depression, anxiety, or having unusual feelings from developing mental illnesses.

Factors of Effectiveness in Italian Forensic Treatment

Over recent years, in Italy, the treatment of mentally ill offenders has undergone profound changes following successive legislative interventions, culminating in Law no. 81/2014, which closed all high-security psychiatric hospitals (OPG) and established a community-based forensic care model managed exclusively by the National Health Service. This model, centred on REMS and territorial mental health services, is unique in the Western context and emphasises rehabilitation, recovery, and time-limited custodial measures. In California, forensic treatment is regulated by the California Penal Code and delivered mainly within high-security state hospitals coordinated by the Department of State Hospitals (DSH), with long average lengths of stay and strong standardisation of security procedures. The two systems therefore differ markedly in structure, duration of stay, and balance between security and rehabilitative goals, raising questions about their respective effectiveness in terms of clinical outcomes, functional recovery, and violent recidivism. This multicentre, prospective cohort study compares Italian forensic patients (Group I) and Californian forensic patients (Group C), enrolled at first entry into forensic care and followed longitudinally for three years with assessments at T0, T1, T2, and T3 using harmonised tools (BPRS 4.0, WHODAS 2.0, HCR-20 V3, SAPROF, DUNDRUM Toolkit, MOAS) and a common data collection form. Primary aims include a detailed epidemiological characterisation of the Italian forensic population and a systematic comparison of outcomes between the Italian and Californian models with respect to violent recidivism, length of stay in forensic settings, clinical and functional improvement, and recovery indicators. Comparative analyses focus on subgroups of participants with psychotic disorders and mental disorders directly related to the index offence, in order to examine differences in outcomes attributable to systemic and organisational features of the two forensic treatment models rather than to diagnostic or criminological heterogeneity.

Clinical Study Evaluating Pharmacogenomics-informed Pharmacotherapy Versus Dosing as Usual in Psychiatric Disorders

A 24-week, patient- and rater-blinded, two-arm, parallel-group controlled, and multi-centre randomized clinical trial (RCT) to establish the benefits of pharmacogenetics-informed pharmacotherapy versus dosing as usual (DAU) in psychiatric patients suffering from mood, anxiety, or psychotic disorders.

Semantic and Syntactic Computerized Analysis of Free Speech

Subtle speech disorganization could be predictive of a transition to schizophrenia of ultra-high-risk patients. The aim of our longitudinal multicenter cohort study is to identify specific linguistic markers of the psychotic transition to validate a french predictive model of this transition using computerized speech analysis techniques

Evaluation of a Brief Intervention to Improve Engagement in Early Intervention Services for Psychosis

Negative experiences with healthcare prior to referral to early intervention services for psychosis (EIS) have been linked to poor engagement and clinical outcomes. Recent research indicates that young adults who come to EIS services thru emergency departments, urgent care, or inpatient services have significantly greater rates of future use of these services as well as more negative perceptions of EIS and diminished engagement in treatment compared to young adults referred to EIS by other pathways. These findings suggest a need for additional support to be provided to EIS patients, especially those with prior negative healthcare experiences, to maximize treatment engagement and outcomes. A recent USA-based trial of a brief intervention addressing barriers to disengagement (Just Do You), including prior negative healthcare experiences, showed promise in improving engagement and recovery. This project seeks to adapt and evaluate the Just Do You intervention to a young adult early psychosis population in Nova Scotia. The investigators aim to recruit young adults from the Nova Scotia Early Psychosis Program to engage in 2 psychotherapy/psychoeducation sessions co-led by a clinician and peer support worker. Following the intervention, the investigators will measure improvements in participants' engagement and recovery to determine the effectiveness of the program. Outcomes between participants with negative prior healthcare experiences and those without will be compared to assess differential impact of the intervention for high-risk sub-groups. This project has the potential to improve patients' engagement in EIS care and enhance recovery outcomes for young adults.

Examining a Digital Health Approach for Advancing Schizophrenia Illness Self-management and Provider Engagement

The effective treatment of schizophrenia is very challenging due to a number of factors. These include issues such as poor engagement with treatment plans and care providers, limited contacts with providers due to under-resourced health services, and the challenges inherent to schizophrenia symptoms. The outcomes of these problems include frequent, lengthy, and costly hospital readmissions, low quality of life, high levels of distress, and difficulties engaging in valued community roles. Digital Health technologies are a promising model to help address these problems. They are a low cost and accessible form of support and have not been substantively developed or studied for people with schizophrenia spectrum illnesses. In this study, the feasibility of one such technology that is in development will be tested: App4Independence (A4i). A4i provides customized coping prompts, peer-peer networking, and a portal that facilitates better provider engagement. This research will provide critical information in the development of this new technology to address a key problem in the field - how to enhance care in a resource-limited context where provider-patient contacts are brief, infrequent, and rely on in the moment recall and self-advocacy by patients. These findings will lay the groundwork for a larger program of research and software development that will (i) validate the technology across multiple sites and, (ii) catalyze engagement with healthcare systems and caregiver networks to scale-out access to this promising resource.