Clinical Research Directory

Time Course of Clozapine-associated Agranulocytosis Over 19 Years

Clozapine is the most effective antipsychotic medication for treatment-resistant schizophrenia, but it carries a rare, potentially life-threatening risk of agranulocytosis (a severe drop in white blood cells), which is why patients undergo regular blood monitoring. Most cases occur in the first months of treatment, and it remains unclear how much risk persists after the first year. This retrospective study will use existing electronic health records from Sheba Medical Center (February 2007 to August 2026) to describe when agranulocytosis occurs among approximately 2,020 patients treated with clozapine over up to 19 years of follow-up. The study will estimate the cumulative incidence and incidence rates across follow-up periods, examine whether risk after the first 18 weeks remains stable over time, and assess age, sex and psychiatric diagnosis as predictors. Each case will be individually reviewed to distinguish clozapine-related events from neutropenia due to cancer or chemotherapy. No patients will be contacted and no treatment will be changed. The findings are intended to inform policy on long-term hematological monitoring of clozapine-treated patients.

Phase 3 Study of HS-10380 for Acute Schizophrenia in Chinese Adults

This is a Phase 3, randomized, double-blind, parallel-group, active- and placebo-controlled, multicenter inpatient study to examine the efficacy and safety of HS-10380 in adult Participants who are acutely psychotic with a Diagnostic and Statistical Manual Fifth Edition (DSM-5) diagnosis of schizophrenia. The primary objective of the study is to assess the efficacy of HS-10380 versus placebo in reducing Positive and Negative Syndrome Scale (PANSS) total scores in adult inpatients with a DSM-5 diagnosis of schizophrenia. The secondary objectives of the study are to evaluate the response rate, improvement in disease severity and symptoms, safety and tolerability.

Cognitive Neurocomputational Task Reliability and Clinical Applications Consortium: Study 3

In Study 3, all tasks and models from Aim 1 will be evaluated in a large community sample of online participants recruited through Prolific. Aim 3 will establish 1) requirements for testing computational algorithms in population-based samples, 2) whether task length is optimal, and 3) whether computational parameters help predict psychopathology (hallucinations and delusions in particular) in the general population, and how these predictors may be impacted by demographic variables, such as race, ethnicity, gender, age and other social determinants of health. Participant demographics will be matched to the U.S. Census 2023 American Community Survey (ACS) data release (updated as available). MPI MacDonald has successfully recruited large online samples for over a decade. Specifically, researchers will recruit two samples of n=2,000 to preregister hypotheses and then n=3,000 to independently confirm those hypotheses. Multiple methods will affirm the highest quality human self-report and behavioral data for online samples. Researchers use Prolific, which is known for high quality research participation, maintaining low levels of bots through strategies such as requiring a photo ID and a waiting period. Second, inclusion criteria will require an approval rating of 90-100% from previous researchers. Participants will complete three sessions, each limited to \~60 min to avoid burnout.

Cognitive Neurocomputational Task Reliability and Clinical Applications Consortium: Study 2

In Study 2, investigators will recruit individuals with schizophrenia (SZ) and or schizoaffective disorder (SZA) and healthy controls (HC) using optimized behavioral tasks to replicate the behavioral findings from Study 1 and to assess additional psychometric properties such as test re-test reliability and practice effects. Investigators will obtain data on: A) clinical symptoms, with detailed assessment of hallucinations and delusions; B) community functioning; and C) functional capacity, allowing us to examine clinical validity. To generate a sample with sufficient variation in hallucinations and delusions, investigators will recruit the following groups that balance feasibility with clinical relevance: A) healthy controls \[HC, N=125\]; B) schizophrenia and schizoaffective disorder \[SZ/SZA, N=200\]). Investigators anticipate a \~20% screen fail/drop-out rate based upon prior studies. Thus, investigators will run an additional 40 SZ/SZA and 15 HC. Investigators will administer tasks optimized in Aim 1 without electroencephalogram (EEG), to this new sample of individuals with SZ/SZA and HC. All participants will be retested after approximately 28 days and repeat clinical assessments. Although the investigators' goal is to shorten task length using the Study 1 analyses, they will administer longer tasks than optimal for public dissemination in Study 2 to determine the minimum number of trials required for acceptable reliability. Study 2 will use the same clinical and functional measures as Study 1.

Online Intervention To Improve Motivation

Participants will complete one online intervention lasting 12 weeks. Each week, they will be asked to complete a 20-30 minute session online. The intervention is targeting improved mood and positive affect in order to support increases in motivation and goal-directed behavior. Before and after the intervention, participants will be asked to complete measures to assess symptoms, mood, and behavior.

Cognitive Neurocomputational Task Reliability & Clinical Applications Consortium (CNTRACS): Study 1

In Study 1, investigators will test the ability of each of the seven paradigms to differentiate between schizophrenia (SZ)/schizoaffective disorder (SZA) and matched healthy control subjects (HC) and to predict individual differences in clinical measures of hallucinations and delusions (as well as measures of function). Investigators will also directly compare the tasks in terms of predictive ability and psychometric properties and determine whether the tasks share variance or explain unique variance. This will include determining whether hallucinations and delusions are best explained by separate underlying processes or by a single process. Investigators will also test whether the model-based parameters from these studies are more precise and sensitive than standard behavioral methods for assessing deficits across psychotic disorders and for predicting hallucinations and delusions (Aim 1). Investigators will also validate key model-based parameters against well-characterized neurophysiological measures using electroencephalogram (EEG) (Aim 4). The data from Study 1 will also be used to optimize (e.g., length, floor, and ceiling effects) tasks for Study 2. To generate a sample with sufficient variation in hallucinations and delusions, investigators will recruit the following groups that balance feasibility with clinical relevance: A) healthy controls (HC) \[HC, N=125\]; B) schizophrenia and schizoaffective disorder \[SZ/SZA, N=200\]). For Study 1, investigators will ensure that 40 patients are unmedicated. Investigators anticipate a \~20% screen fail/drop-out rate based on our prior Cognitive Neuroscience Test Reliability and Clinical Applications for Schizophrenia Consortium (CNTRACS) studies. Thus, investigators will run an additional 40 SZ/SZA and 15 HC. All sites have experience recruiting patients in each of these groups as indicated by our past successful studies, and the fact that investigators have been able to recruit patients with significant hallucinations and delusions in all groups. Investigators will also validate key model-based parameters against well-characterized neurophysiological measures using electroencephalogram (EEG) (Aim 4). The data from Study 1 will also be used to optimize (e.g., length, floor, and ceiling effects) tasks for Study 2. To generate a sample with sufficient variation in hallucinations and delusions, investigators will recruit the following groups that balance feasibility with clinical relevance: A) healthy controls (HC) \[HC, N=125\]; B) schizophrenia and schizoaffective disorder \[SZ/SZA, N=200\]). For Study 1, investigators will ensure that 40 patients are unmedicated. Investigators anticipate a \~20% screen fail/drop-out rate based on our prior Cognitive Neuroscience Test Reliability and Clinical Applications for Schizophrenia Consortium (CNTRACS) studies. Thus, investigators will run an additional 40 SZ/SZA and 15 HC. All sites have experience recruiting patients in each of these groups as indicated by our past successful studies, and the fact that investigators have been able to recruit patients with significant hallucinations and delusions in all groups.

Brain Imaging of DSP-2342

The investigators aim to determine the effects of a novel drug on brain function and brain chemistry in patients with schizophrenia.

Building a Computational Model of Auditory Hallucinations

Some people hear voices or sounds that other people cannot hear; these are called auditory hallucinations. The study aims to understand what is happening in the brain when this occurs and will use brain scans to learn more. Greater understanding should help develop better treatments in the future.

Ultrasound Assessment of Gluteal Muscle in Patients Receiving Depot Antipsychotics and Healthy Volunteers

This observational study will use ultrasound to assess the gluteal musculature in patients receiving depot antipsychotic medication and in healthy volunteers. The study aims to improve knowledge about anatomical conditions relevant to intramuscular depot injections.

Multi-target TMS for Schizophrenia Negative Symptoms

This randomized controlled trial (RCT) is the first to evaluate the efficacy and safety of a multi-target TMS protocol targeting the right orbitofrontal cortex (R-OFC), left dorsolateral prefrontal cortex (L-DLPFC), and left inferior parietal lobule (L-IPL) for negative symptoms of schizophrenia.

Disorders of the Sense of Self and Physical Activity

Schizophrenia (SZ) patients with metabolic syndrome, patients with vestibular syndrome, and patients with borderline personality disorder, would benefit from physical activity (PA). Yet patient adherence to PA is low, at least in the case of SZ. the investigators work and the literature lead the investigators to consider that, in addition to motivational aspects, disorders of the bodily sense of self could play a role in this lack of adherence. Simply walking involves visual movements related to the self, which must be distinguished from movements in the environment. This means a distinction between self and not-self. Furthermore, these movements are all the more difficult to distinguish as they may also result from the fact that hidden objects become visible as a result of our own movement. In all sense-of-self disorders can themselves affect physical training, and the investigators will measure them in the first stage. In the second stage, the investigators will apply a standard, risk-free PA protocol by walking (3x3 sessions of 30 min). the investigators will test the impact of physical training on the sense of self under different conditions, with one environment minimizing self-related movement, vs. 2 environments with a variable level of enrichment (i.e. hidden objects inducing more or less self-related movement). At the end of the protocol, the investigators will offer participants who wish to take part in an ancillary study, i.e. a walking session with mixed-reality goggles. These will superimpose a luminous flux on the periphery of the visual field. According to results obtained in the laboratory, this flux could restore sensory mechanisms impaired in schizophrenia. the investigators will use these glasses in the most difficult condition for the patient, and verify their impact.

Basal Stimulation Therapy in Adults With Schizophrenia Requiring Institutional Care

The aim of the study is to obtain knowledge of the impact of basal stimulation therapy on the health status of adults suffering from schizophrenia and requiring permanent institutional care. The use of basal stimulation therapy in many European centres for several decades, combined with the limited amount of scientific evidence, justifies undertaking the proposed research. Available evidence indicates reduced anxiety and improved quality of life. No such studies have previously been conducted in institutionalized patients with schizophrenia.

A Study to Evaluate the Long-term Safety of HS-10380 in Patients With Schizophrenia

The primary purpose of this open-label phase 3 study is to evaluate the safety of HS-10380 on the incidence, severity, relationship to investigational product of adverse events (AE), serious adverse events (SAE), and adverse events leading to study drug discontinuationin Chinese adult participants with schizophrenia.

Simulation-Based Schizophrenia Training in Nursing Education

This study aims to examine the effect of a schizophrenia scenario-based simulation on nursing students' knowledge, empathy, and caregiving competence. The study uses a single-group pre-test/post-test (quasi-experimental) design. Nursing students enrolled in a Mental Health and Psychiatric Nursing course at a foundation university in Istanbul, Türkiye, who have not previously participated in a similar simulation, are invited to take part. Before the simulation, participants complete a set of questionnaires assessing their knowledge about schizophrenia, empathy level, and caregiving competence. They then take part in a structured simulation session involving a standardized patient portraying a person with schizophrenia. The session includes a preparation phase, a prebriefing session, a 15-minute clinical encounter in which the student conducts a therapeutic interview and mental status examination, and a debriefing session guided by a structured reflective model. Immediately afterward, participants complete the same questionnaires again, along with a scale measuring their perception of the simulation's educational effectiveness. The purpose of the study is to determine whether this type of simulation-based training improves nursing students' knowledge, empathy, and confidence in caring for individuals with schizophrenia, and to contribute evidence on the use of simulation in psychiatric nursing education.

Snoezelen Therapy in Adults With Alcohol Dependence and Adults With Schizophrenia

The purpose of the study: obtaining knowledge about the impact of Snoezelen® therapy on the health of adults suffering from schizophrenia and requiring permanent institutional care, adults suffering from schizophrenia and adults (women) addicted to alcohol. The main questions it aims to answer are: Does Snoezelen therapy improve the health of adults suffering from schizophrenia and requiring permanent institutional care, adults suffering from schizophrenia and adults (women) addicted to alcohol? The participant will participate in Snoezelen® therapy for 6 or 12 weeks, 2 times a week (30 minutes each session).

Behavioral Impact and Neural Correlates of Network-based Brain Stimulation in Schizophrenia

The primary aims of this study are to investigate the behavioral effects of applying targeted transcranial magnetic stimulation (TMS) to a node of the brain network subserving attention in schizophrenia and schizoaffective disorder and to correlate these effects to changes in brain network connectivity. Assumptions: -Cerebral activity can be investigated through the correlated activity of cortical nodes that constitute functional brain networks -Behavior can be correlated to the strength of correlated activity between and within nodes of these cortical networks -TMS to targeted nodes leads to changes in patterns of activity in these cortical networks Hypothesis: TMS to a node of the attention network in schizophrenia or schizoaffective disorder will influence network connectivity leading to measurable and predictable effects on attention.

TOPUS - Testing an Implemented Intervention to Reduce Duration of Untreated Psychosis

This study examines whether an early-detection program for psychosis can shorten the time patients remain untreated after the first appearance of psychotic symptoms, and whether such a reduction improves later functioning for people with first-episode schizophrenia. Psychosis involves symptoms such as hallucinations and delusions. When these symptoms are recognized and treatment begins, most patients improve. However, many individuals live with psychotic symptoms for months-or even longer-before receiving care. This period is known as the duration of untreated psychosis (DUP). A long DUP has repeatedly been linked to poorer long-term outcomes, but it is still unclear whether DUP itself causes worse outcomes or simply reflects different illness courses. In Denmark, Region Zealand has implemented a large-scale early-detection effort. This includes public awareness campaigns and a specialized team that identifies people with emerging psychosis and helps them start treatment quickly. The Capital Region of Denmark provides usual care without these additional initiatives. This situation makes it possible to compare two regional systems that differ in their approach to early detection but provide the same specialized treatment once patients enter care. The study follows a quasi-experimental design, recruiting adults (18+) who receive a first diagnosis of a schizophrenia-spectrum disorder within the OPUS early-intervention programs in the two regions. No interventions are assigned by the research team; participants receive standard clinical care. Researchers conduct interviews to establish how long psychotic symptoms were present before treatment began and to assess functioning and symptoms over a two-year follow-up period. Functioning, symptoms, cognition, and treatment factors will be examined at baseline and at follow-ups. The study addresses three questions: Whether early-detection efforts in Region Zealand reduce the duration of untreated psychosis compared with usual detection. Whether a shorter duration of untreated psychosis leads to better functional and clinical outcomes fifteen months after treatment begins. How DUP can best be defined and measured so that it reliably predicts later outcomes. Results may provide evidence for whether early-detection services improve timely access to care and whether reducing the duration of untreated psychosis contributes to better long-term functioning. The study may also help establish clearer international standards for how DUP should be measured in both research and clinical practice.

A PET/MRI Study of Cobenfy on Dopamine Transmission in Schizophrenia

This is a single site clinical trial in which 12 participants with schizophrenia will be randomized to one of three doses of treatment with Cobenfy for 5 weeks. \[18F\]DOPA PET scans will be obtained before and after treatment to examine the effects of Cobenfy on dopamine transmission. The overall objective of the current study is to measure Cobenfy's ability to engage its putative target (DA transmission/synthesis capacity in the striatum and midbrain as measured by \[18F\]DOPA Kicer (\[18F\]DOPA relative uptake rate)).

Bioequivalence Study to Compare Cariprazine 1.5 mg Hard Capsules (1.5 mg Cariprazine Hydrochloride) Versus Reagila® 1,5 mg Hartkapseln (Hard Capsules) (Cariprazine)

Single dose oral bioequivalence study of Cariprazine 1.5 mg Hard Capsules (1.5 mg Cariprazine hydrochloride) and Reagila® 1,5 mg Hartkapseln (Hard Capsules) (Cariprazine) in healthy adult human participants under fasting conditions.

The Effect of ACT-Based Nursing Interventions on Social Cognition, Emotion Regulation and Psychological Flexibility in Patients With Schizophrenia

This randomized controlled trial aims to evaluate the effect of Acceptance and Commitment Therapy (ACT)-based nursing interventions on social cognition, emotion regulation, and psychological flexibility in individuals diagnosed with schizophrenia. The study will be conducted at Erzincan Community Mental Health Center (TRSM) between October 2026 and January 2027. A total of 64 participants (32 experimental, 32 control) will be recruited from schizophrenia patients registered at the center. The experimental group will receive 8 structured group sessions based on ACT principles integrated into nursing practice (45-60 minutes per session, once weekly), while the control group will receive routine care only. Pre-test and post-test measurements will be obtained using the Observable Social Cognition Rating Scale (OSCARS), the Difficulties in Emotion Regulation Scale-Brief Form (DERS-16), and the Acceptance and Action Questionnaire-II (AAQ-II).

ACT-Based Psychoeducation for Caregivers of Patients With Schizophrenia

This randomized controlled trial aims to examine the effects of an Acceptance and Commitment Therapy (ACT)-based psychoeducation program on expressed emotion, perceived family burden, and psychological flexibility among caregivers of patients with schizophrenia attending a Community Mental Health Center. The main questions this study aims to answer are: * Does ACT-based psychoeducation reduce expressed emotion among caregivers of patients with schizophrenia? * Does ACT-based psychoeducation reduce perceived family burden among caregivers of patients with schizophrenia? * Does ACT-based psychoeducation improve psychological flexibility among caregivers of patients with schizophrenia? Researchers will randomly assign eligible caregivers to either an intervention group receiving an 8-session ACT-based psychoeducation program or a control group receiving routine care. Participants will: * Complete assessment measures before the intervention (pre-test). * Participate in 8 ACT-based psychoeducation sessions if assigned to the intervention group. * Continue receiving routine care if assigned to the control group. * Complete assessment measures immediately after the intervention (post-test). * Complete follow-up assessments at 1 month and 3 months after the intervention.

Cognitive Rehabilitation With Immersive Virtual Reality (IVR) in Schizophrenia: a Pilot Randomized Waiting List Controlled Feasibility Study

Virtual reality-based rehabilitation has recently gained increasing attention in the field of cognitive rehabilitation, allowing patients to engage in simulated real-life scenarios within a safe and controlled setting. The feasibility and safety of immersive VR-based cognitive rehabilitation in individuals with schizophrenia is currently insufficiently explored. This study seeks to evaluate whether immersive immersive virtual reality-based rehabilitation can be safely and practically implemented in a community psychiatric setting. The study also aims to explore preliminary effects on negative symptoms, cognitive performance, and global functioning compared with treatment as usual in a waiting-list control group.

Precision HD-tACS for Enhancing Sensory Experience in Schizophrenia

To ensure unified sensory perception, the brain must link information from different senses across time and space. This unification of perception often referred to as a perceptual "binding constraint" is a prerequisite for any organized perception. Patients with schizophrenia exhibit deficits in the spatiotemporal binding of sensory information . Electroencephalography (EEG) studies highlight the role of delta-theta oscillatory dynamics (2-8 Hz) in neuronal entrainment processes underlying spatiotemporal binding, which enables the formation of a coherent and organized perceptual representation . These same dynamics are disrupted in schizophrenia . In tasks assessing perceptual binding, such alterations manifest as widened temporal binding windows, reflecting impaired temporal structuring of visual events. Physiologically, these disruptions may stem from impaired feedback mechanisms within the cortico-cerebello-thalamo-cortical (CCTC) loop. Schizophrenia patients also exhibit functional and structural deficits in the pulvinar and frontal cortex, key nodes of the CCTC loop . Recent technical advances in transcranial neurostimulation have reinforced its potential as a therapeutic tool. High-definition transcranial alternating current stimulation (HD-tACS) now enables individualized modulation of pre-identified neural networks , including targeted interventions for schizophrenia . Based on a personalized stimulation protocol, this research project proposes precision HD-tACS therapy, tailored for each patient according to their delta-theta peak frequency measured via EEG and the optimal functional stimulation site identified with functional MRI (fMRI). Stimulation will be applied functionally, i.e., while the patient performs a cognitive task. Structural connectivity alterations have been observed in fronto-thalamic, thalamo-cingulate, and cortico-cerebellar pathways in schizophrenia, potentially underpinning temporal and spatial binding deficits. Assessing the integrity of the CCTC loop with diffusion tensor imaging (DTI) will allow quantification of fiber coherence and white matter density connecting cortical and subcortical regions within this network.To evaluate both baseline perceptual deficits and the potential improvements induced by stimulation, a control group of healthy participants will be included.

Developing a Virtual Reality-assisted Intervention for Emotion Regulation Difficulties in Psychosis

Supporting people with psychosis to manage their emotions using virtual reality Many people who have experienced psychosis feel overwhelmed by their emotions. Emotions get in the way of doing what matters to them. They want support to manage emotions differently. There is evidence that people with psychosis find talking therapies that teach skills for managing emotions helpful. People said it helped them to understand and manage their emotions. However, they also wanted more help to apply skills they learned to their lives. It is hard to help people to use therapy skills in real-life situations. Therapists cannot be present when the skills are needed. One solution is to use virtual reality (VR) to bridge the gap between the clinic and real-life. VR involves using a headset to see and hear a very life-like computer-generated simulation of everyday life situations. People with psychosis find VR therapies engaging and helpful. It can feel safer to try things out in VR. Guided by the feedback of people with psychosis, this research will evaluate a novel therapy to help people with psychosis manage their emotions. Face-to- face therapy will be combined with VR so that people can practice emotion regulation skills safely with "live" coaching from a therapist. This should support people to use these skills when they need them. Fifteen people with psychosis will be offered the therapy. Everyone will be asked what they think of it and complete questionnaires before and after therapy to see what impact it had on their lives. A lived experience advisory group will support all aspects of the research process.