Clinical Research Directory

Cognitive Strategies in Early Psychosis 2

The goal of this clinical trial is to learn more about decision making in psychosis spectrum disorders, like schizophrenia. Participants will be people who have had symptoms of a psychosis spectrum disorder start within the last five years. The investigators will study how two study agents change decision making in people with psychosis, by asking participants to complete some brain games on the computer before and after taking the study agents. The investigators hope to improve our understanding of psychosis to help people in the future. The main research questions are: * Does a single dose of modafinil change how people with psychosis play the brain games? * Does a single dose of d-serine change how people with psychosis play the brain games? * Does a single dose of modafinil change brain activity? * Does a single dose of d-serine change brain activity? Participants will: * Complete an interview and self-report questionnaires. * Complete safety screening activities, like a blood draw, a urine drug test, and an alcohol breathalyzer test. * Complete functional Magnetic Resonance Imaging (fMRI) scans. fMRI uses magnets to take pictures of the brain. There will be six scanning appointments in the study, with two scans each. Appointments will be about a month apart. * Take a single dose of a study agent during each scanning appointment. The study agent will be taken after the first fMRI. There are three study agents in total: modafinil, d-serine, and a placebo. Each participant will take each study agent twice during the study. * Play brain games on a computer that measure decision making, thinking, and problem solving skills

Strengthening Care in Collaboration With People With Lived Experience of Psychosis in Uganda

Background: Mental health services are most effective and equitable when designed, delivered, and evaluated in collaboration with people with lived experience of mental health conditions. Unfortunately, people with lived experience are rarely involved in health systems strengthening or are limited to specific components (e.g., peer helpers) rather than multi-tiered collaboration in the continuum of health services (e.g., ranging from home- to community- to clinic-based services). Moreover, programs that do involve people with lived experience, typically involve people with a history of a substance use conditions or common mental disorders. In contrast, the collaboration of people with lived experience of psychosis is especially rare. A pilot cluster randomized controlled trial will be conducted in urban and peri-urban areas around Kampala, Uganda, to evaluate the benefits of an implementation strategy for mental health services with engagement of people with lived experience of psychosis throughout the home-to-community-to-clinic care continuum, this is a hybrid type-III implementation-effectiveness pilot focusing on the differences in implementation strategy. This implementation strategy, entitled "Strengthening CAre in collaboration with People with lived Experience of psychosis in Uganda", will include training people with lived experience of psychosis using PhotoVoice and other methods to participate at three levels: in-home services, community engagement, and primary health care facilities. The investigators will compare a standard task-sharing implementation arm using training by mental health specialists with an experimental implementation arm that includes collaboration with people with lived experience. The primary objective is to evaluate the feasibility and acceptability of this strategy in the context of assuring safety and wellbeing of people with lived experience of psychosis who collaborate in health systems strengthening. By collaborating on health systems strengthening across these multiple levels, we foresee a more in-depth contribution that can lead to rethinking how best to design and deliver care for people with lived experience of psychosis. Successful completion of this pilot will be the foundation for a fully powered trial to evaluate the benefits of multi-level collaboration with people with lived experience of psychosis.

IVIG and Rituximab in Antibody-associated Psychosis - SINAPPS2

A randomised phase II double-blinded placebo-controlled trial designed to explore the utility of immunotherapy for patients with acute psychosis associated with anti-neuronal membranes (NMDA-receptor or Voltage Gated Potassium Channel). Primary objective: To test the efficacy of immunotherapy (IVIG and rituximab) for patients with acute psychosis associated with anti-neuronal membranes. Secondary objective: To test safety of immunotherapy (IVIG and rituximab) for patients with acute psychosis associated with anti-neuronal membranes.

Value of Gym-based Exercise Training for Young Adults Receiving Antipsychotic Medication: The Vega Trial

This is a multicentre, pragmatic, randomised controlled trial to estimate the effect of a 4-month gym-based exercise training program on 1) patient-rated personal recovery (primary outcome), 2) Health-related quality of life, behavioral and functional symptoms, and cardiometabolic risk factors (secondary outcomes) in young adults with psychotic disorders. Four-hundred antipsychotic-treated young adults (between the age of 18 and 35), who are capable to undertake an exercise program (potentially with a friend or family member where possible) will be recruited from outpatient treatment units and mental health services. Participants will be randomised to treatment as usual or exercise at a 2:1 ratio in favor of exercise. Outcomes will be measured at baseline and at 4, 6 and 12 months after randomisation, by researchers masked to participant allocation.

A Study to Evaluate Safety and Efficacy of KarXT + KarX-EC as a Treatment for Psychosis Associated With Alzheimer's Disease (ADEPT-5)

The purpose of this study is to evaluate KarXT + KarX-EC as a treatment for psychosis associated with Alzheimer's disease.

Neurobehavioral Mechanisms of Social Isolation and Loneliness in Serious Mental Illness

The proposed research will test the hypothesis that objective social isolation and loneliness are linked to neurobehavioral mechanisms involved in social perception and motivation in individuals with and without serious mental illness. Moreover, it will investigate the specific dynamic interactions among these experiences in daily life and how they, and their neurobehavioral predictors, are linked to day-to-day functioning. The findings of this project could provide novel targets for therapeutics aimed at improving functioning and overall quality of life in individuals with serious mental illnesses, as well as quantitative phenotypes for use in early detection efforts.

Acute Psychiatric Care at Home for Lower-risk Patients With Acute Psychiatric Illness Who Require Inpatient Care

The goal of this pilot randomized controlled trial is to learn if adult patients with acute psychiatric conditions can receive hospital-level care at home. The main question it aims to answer is: 1\. Estimate the eligibility rate for BHH among screened patients. What percentage of eligible patients agree to enroll in behavioral health home hospital (intervention)?

Early Psychosis: Investigating Cognition

The project aims to explore changes in brain chemistry in individuals who have recently experienced psychosis. Recent research suggests that chemicals in the brain, specifically one called glutamate, may behave differently in people who have experienced psychosis compared to those who have not. It is also known that some individuals with psychosis can find tasks involving memory and attention more challenging. This study aims at understanding how brain chemistry is linked to memory and attention, and if this is different between people who have and have not experienced psychosis. The study will also investigate how a commonly used brain stimulation technique might help people with psychosis and other conditions by altering brain chemistry for a very short period. Non-invasive brain stimulation using very weak electrical stimulation has been used to help improve symptoms in individuals with psychosis and many other conditions, and has been shown to alter brain chemistry for a few hours after stimulation. However, it does not work for everyone. It will be investigated if levels of glutamate can predict whether brain stimulation will help an individual or not. In other words, the study investigates if glutamate can be used as a marker for tailoring treatments. This project also aims to collect personal experiences or challenges that individuals with psychosis face. This information will be gathered through interviews. This will help to understand what specific difficulties individuals have, such as with certain aspects of memory and attention. The interview will also gather opinions and concerns about brain imaging and brain stimulation and current understandings of chemicals in the brain. For example, the study will explore why individuals may not want to take part in brain imaging or brain stimulation.

Examining the Effects of Estradiol on Neural and Molecular Response to Reward

This proposal will examine the effects of estradiol administration on perimenopausal-onset (PO) anhedonia and psychosis symptoms as well as on brain function using simultaneous positron emission tomography and functional magnetic resonance imaging (PET-MR).

Ketosis Impact on Signs & Symptoms of Schizophrenia and Bipolar disorderS

The goal of this clinical trial is to learn if a ketone drink can improve signs and symptoms of patients with a schizophrenia-spectrum disorder (SSD), or a bipolar-spectrum disorder (BD). The main questions it aims to answer are: Does a ketone drink improve information processing in patients with SSD/BD? Other questions it aims to answer are: Does a ketone drink improve cognitive functioning in patients with SSD/BD? Does a ketone drink improve metabolism and inflammation in patients with SSD/BD? Does a ketone drink affect circadian rhythm in patients with SSD/BD? Research will compare the effects of the ketone drink with that of an isocaloric carbohydrate drink in the same patients ('cross-over'). Participants will: 1. drink a ketone drink and (after a wash-out period) an isocaloric control drink (randomized order); after each drink: * EEG/EMG to determine information-processing parameters (PPI and P300) * cognitive tests * visual analog scale of mood, energy levels, ability to focus * indirect calorimetry to determine use of energy substrate * blood draws 2. for 5 consecutive days: * wear a continuous glucose monitor (CGM) * wear a non-invasive passive sweat biomarker sensor (EnLiSense device) * register a diet and nicotine diary * saliva sampling (max. 5x/day)

Efficiency of a Composite Personalised Care on Functional Outcome in Early Psychosis

Chronic psychosis, including schizophrenia is now viewed as a progressive disorder where cognitive deficits predate the clinical onset. Early intervention programs improve the general outcome with staged care strategies, supporting the view that the period before and around the first episode of psychosis is a window of opportunity for improving its functional recovery. Pioneering epigenetic analyses indicate that psychosis onset involves oxidative stress and inflammation suggesting that neuroprotective strategies could limit or even prevent the onset of or the transition into a chronic disorder. Several biological factors associated with the emergence of psychosis can all be rectified by using safe and easily accepted supplements including alterations folate deficiency/hyperhomocysteinemia; redox imbalance and deficit in polyunsaturated fatty acids (PUFA). The prevalence of these anomalies (20-30%) justifies a systematic detection and could guide personalised add-on strategy. Cognitive remediation improves quality of life (QoL) and functional outcome in patients with chronic psychosis. It would even be more efficacious in the early phase of psychosis by tackling the negative impact of psychosis on education achievement and employment. However, cognitive dysfunctions are often overlooked in patients at ultra-high risk (UHR) for psychosis and patient with a first episode of psychosis (FEP) and cognitive remediation is not always accessible. New technologies can provide us with youth-friendly, non-stigmatising tools, such as applications with cognitive strategies, motivational tools and functioning guidance personalised according to the need of each individual. Patients can have access to it, wherever they live. Early psychosis can be associated with inflammation, metabolic deficiency, as well as early structural brain anomalies that reflect brain plasticity abilities and could influence the prognosis and response to cognitive training. The study hypothesis is that promoting neuroplasticity by cognitive training and personalised virtual psychoeducation guidance could attenuate or reverse early cognitive deficits and improve the overall functional outcome in young patients UHR or FEP and that this effect is modulated by individual brain plasticity abilities. The overall objective of PsyCARE\_trial is to improve early intervention in psychosis by providing a composite personalised care (CPC) that will enable personalised cognitive training and psychoeducation guidance, adapted to individuals' needs, cognitive abilities and biological background.

Youth Nominated Support Team

This study aims to adapt the current Youth-Nominated Support Team (YST) manual used to treat suicide risk for people at clinical high risk for psychosis.

Pilot Study of Sensor-Informed Smartphone-based Mental Health Interventions for Mood in Early Psychosis

The aim of this trial is to evaluate the feasibility and preliminary efficacy of using passive smartphone sensors to detect moments of heightened negative mood and inform the timing of brief mental health interventions, such as mindfulness exercises and psychoeducation, in adults with early psychosis.

Effects of Action-Based Cognitive Remediation on Substance Misuse in Early Phase Psychosis

Psychotic disorders impact 4.6 people per 1000 globally, with approximately 1.5 million Canadians affected. The age of onset for psychotic disorders often begin during the critical years of youth and early adulthood, resulting in significant challenges for individuals and their families, including difficulties with thinking, relationships, and overall well-being. They also carry significant economic costs, both for health care and lost productivity. Early intervention services have been shown to improve outcomes when provided during the first few years of illness known as early phase psychosis (EPP). However, substance use, especially alcohol and cannabis, can interfere with the effectiveness of these services. Many young people with psychosis misuse these substances, which can harm brain development, worsen symptoms, reduce medication use, and lower quality of life. Despite understanding the risks, there are few effective ways to reduce substance misuse in patients with EPP. One promising approach to reducing substance misuse in this population is cognitive remediation therapy, which helps improve thinking skills and everyday functioning. Studies have found that some cognitive remediation therapies can help reduce alcohol use in chronic schizophrenia, but there is limited research targeting the EPP population. Our research team at the Nova Scotia Early Psychosis Program recently completed a pilot study that indicated a therapy called Cognitive Enhancement Therapy (CET) helped participants reduce their problematic alcohol and cannabis use. However, challenges with recruitment and lower attendance rates noted towards the end of the 6-month therapy course suggests that patients with EPP would benefit more from a therapy with a shorter timeframe. Alternatively, Action-Based Cognitive Remediation (ABCR) targets the same cognitive domains believed to help reduce substance use as CET, but has a shorter, more concise schedule. ABCR cover 16 sessions delivered bi-weekly for 2 months, compared to 45 sessions over 6 months of CET. ABCR has been tested in the EPP population and has shown positive results when delivered in person, hybrid and remotely. Although this therapy is demonstrating benefits for patients including improvement in daily functioning and social cognition, its effects on substance misuse have not been researched. This study aims to investigate whether treatment with ABCR helps patients with EPP reduce their alcohol and/or cannabis use.

Cannabis Potency Effects on Brain White Matter in Early Phase Psychosis

Canada reports some of the highest rates of cannabis use in our youth and young adult populations, among all the developed countries. Recent Health Canada surveys report that 27% of 16-19-year-olds and 32% of 20-24-year-olds have used cannabis in the past 30 days, with 16-24-year-olds showing the highest rates of daily or near-daily use. Unfortunately, cannabis use has also been found to be a risk factor for the development of a psychotic disorder in emerging adults, and in those who develop psychosis and continue cannabis use, there is a significant effect on long term outcomes. This includes the severity of symptoms, risks of relapse (being hospitalized) and not reaching a level of functioning that would be expected. Lifetime experience with cannabis is greater than 80% in young adults with early phase psychosis (EPP; the first 5 years of a psychosis illness) with up to 30% of Canadian EPP patients meeting criteria for a diagnosis of cannabis use disorder (CUD) at entry to care. A recent Canadian population-based study found that cannabis use disorder associated to psychosis has risen from 3.7% pre-2018 to 10.3% at present. There has been a significant increase in Δ9-tetrahydrocannabinol (THC) levels in cannabis products available globally over the years, with popular cannabis products available start as high as 18% THC in Canada. However high potency cannabis carries a more significant risk for psychosis development, as well as higher risk for cannabis dependence and other severe mental health issues. A major gap in the research is a specific focus on cannabis potency on brain white matter (WM) in youth and young adults, and if there are any potential treatment strategies that could be used to influence any of these cannabis WM effects. To address this, a medication called metformin, that is already used in psychosis to help with side effects of antipsychotic medications, will be used as it has also shown promise to influence WM changes in other illnesses. This project is thus focused on naturalistic cannabis potency effects on WM in emerging adults in EPP (divided into three groups; those using high potency cannabis, low potency cannabis, and minimal cannabis use) and treating them with metformin for 6 months and assessing effects on neuroimaging, cognitive and clinical variables. The purpose of this pilot feasibility study is to inform the development/refinement of an intervention protocol, and not to test potential effects or mechanisms as the sample size will have insufficient power to perform an in-depth analysis. The results of this work will inform our research strategy development and assess feasibility of our novel methodological approach. Participants will: 1. Visit the clinic at baseline, 3 months (only Timeline Follow-Back Assessment administered), and 6 months post baseline to complete substance use and mental health questionnaires, and cognitive assessments 2. Complete an MRI scan at baseline and 6 months 3. Take Metformin every day for 6 months

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.

Study of Language Disorders and Interactions Between Mnesic Capabilities and Semantic Competencies in Patients With Psychosis

This research concerns the study of language disorders of patients present in the spectrum of psychosis. It is indeed accepted that psychotic disorders are associated with language difficulties, which are only poorly highlighted thanks to reusable tools in clinical practice. These language disorders impact communication, and concern many linguistic domains, thus covering phonology, lexicon, semantics, morphosyntax and pragmatics. It therefore seems relevant to characterize these language disorders and to assess to what extent they interact with the other symptoms of the pathology, in particular the course of the thought disorder and the neuropsychological symptoms. In addition, this study is particularly interested in the interactions between working memory capacities and those related to syntax. It is intended for different patients suffering from psychotic disorders of different intensities, treated in the Psychotherapeutic Center of Nancy. Patients suffering from at-risk mental state (ARMS), first episode of psychosis (FEP) or schizophrenia will benefit from a complete language assessment, evaluating each domain mentioned above, on the expressive and understanding sides. The results of the language assessment will be compared with those of a control group in the same tests. They will also be analyzed with regard to the neuropsychological and psychiatric elements noted in the patient's medical file, in order to highlight possible associations between language skills, neuropsychological and psychiatric symptoms in this patient population.

Immune Mechanisms of Antipsychotic Treatment Response

The aim of this study is to investigate the role of the immune system in psychotic symptoms and their response to treatment. The investigators will collect blood and cerebrospinal fluid samples from participants with psychosis symptoms who are about to start or change to a new regular antipsychotic treatment as well as a control group for comparison. Participants will be assessed at two main timepoints, at visit 1 (Week 0) and at visit 2 (4 +/-2 weeks). For participants with psychosis symptoms visit 1 will take place at the start or change of antipsychotic medication. The studies goal is to identify biomarkers that can aid in diagnosis, prognosis, treatment selection, and tracking treatment response. The investigators aim to recruit participants from the following groups: 1. Individuals with psychosis symptoms presenting to acute or outpatient services who are due to be started on or change to a new regular antipsychotic medication. 2. Age- and sex-matched control participants without neuropsychiatric disease. Findings could potentially impact the treatment of psychotic illnesses by offering mechanistic insights into targeted immune-based interventions for these disorders through high-resolution immunophenotyping techniques alongside targeted immunological assays. Ultimately, the research aims to contribute valuable resources for future studies exploring the connection between immune processes and neuropsychiatric conditions.

Improving Health Literacy in Patients With Schizophrenia Spectrum Disorder

The Impact of Health Literacy on the Attitudes toward Pharmacological Treatment in Patients with Schizophrenia Spectrum Disorder This interventional study is aimed at: * assessing and improving the health literacy and * assessing the attitude towards treatment of patients with schizophrenia spectrum disorders while they are admitted to the inpatient psychiatric unit.

The Mouth Matters in Mental Health Trial -2

This clinical trial will evaluate the effectiveness and cost-effectiveness of a link work intervention for supporting people with severe mental health difficulties to attend a routine dental appointment. There are two main outcomes, namely: i) attendance at a routine dental appointment; and ii) oral health quality of life. The main predictions are that: 1. The link work intervention plus treatment as usual will lead to greater likelihood of attendance at a routine dental appointment, compared with treatment as usual alone. 2. The link work intervention plus treatment as usual will lead to better oral health quality of life, compared with treatment as usual alone. 3. The link work intervention plus treatment as usual will be cost-effective compared with treatment as usual alone.

Cerebellar Modulation of Cognition in Psychosis

The goal of this clinical trial is to learn about cognition in psychotic disorders (schizophrenia, bipolar disorder, and schizoaffective disorder). The main question it aims to answer is: Can we use magnetic stimulation to change processing speed (how quickly people can solve challenging tasks). Participants will be asked to perform cognitive tasks (problem-solving) and undergo brain scans before and after transcranial magnetic stimulation (TMS). TMS is a way to non-invasively change brain activity. Forms of TMS are FDA-approved to treat depression and obsessive compulsive disorder. In this study, we will use a different form of TMS to temporarily change brain activity to observe how that changes speed in problem-solving.

A Novel Blood Test as a Biomarker in Mental Health

This longitudinal, observational study aims to assess whether the characteristics of a novel blood peripheral biomarker can serve as indicators for depression and schizophrenia in patients at the Royal Columbian Hospital Psychiatric Clinics. The study will evaluate whether changes in these biomarker characteristics can help distinguish between depressed patients who do or do not respond to treatment and between individuals experiencing a single psychotic episode and those at risk of progressing to schizophrenia. To achieve this, blood samples and standardized mental health assessments will be collected across three study visits from up to 500 participants, grouped into two study arms based on their diagnosis: Depression (DEP) or Psychosis/Schizophrenia (PSY).

Acceptability, Feasibility and Preliminary Outcomes of the Kiso Mind App for Outpatients With Schizophrenia Spectrum Disorders

The Kiso pilot study is a randomized controlled trial to test the acceptability and feasibility of a novel digital intervention, namely the Kiso Mind smartphone app. A parallel-group design is utilized. Participants either receive access to the Kiso Mind intervention and treatment-as-usual (TAU) in the experimental condition or receive treatment as usual (TAU) in the control condition. The intervention is designed for participants diagnosed with either schizophrenia (F20.0) or schizoaffective disorder (F25.0) according to the ICD-10. To examine acceptability, feasibility, and preliminary effectiveness, both self-report and rater-based assessments are administered at baseline (T0) and at the end of the 12-week intervention period (post-intervention T1). Lastly, a qualitative interview will be conducted with participants from the experimental condition. The primary outcome of the present study is the acceptability and feasibility of the Kiso Mind app. The secondary outcome consists of general psychopathology, and positive-, negative-, depressive symptoms, as well as social functioning and self-efficacy ratings.

Comparison of Accelerated Intermittent Theta Burst Stimulation vs High Frequency Transcranial Magnetic Stimulation (Hf-rTMS) on Cognitivesymptoms in Treatment-resistant Schizophrenia

This randomized, double-blind, sham-controlled trial compares three brain stimulation approaches-accelerated intermittent theta burst stimulation (aITBS), high-frequency repetitive transcranial magnetic stimulation (HF-rTMS), and sham stimulation-for treating cognitive deficits in treatment-resistant schizophrenia. Ninety patients receiving clozapine will be randomized 1:1:1 to receive 20 sessions over 4 weeks targeting the dorsolateral prefrontal cortex. The primary outcome is change in cognitive function measured by B-CATS score at 2, 4, and 12 weeks. Secondary outcomes include social cognition, symptom severity, brain metabolism (FDG-PET), and inflammatory biomarkers.