Clinical Research Directory

The OPUS YOUNG Trial. Early Intervention Versus Treatment as Usual for Adolescents With First-episode Psychosis

The OPUS YOUNG (OY) study investigates the efficacy of early intervention service versus treatment as usual (TAU) for adolescents aged 12-17 years with a first-episode psychosis. In Denmark, the yearly incidence of schizophrenia in youth below the age of 18 years has increased from 137 in 2000 to 477 in 2016. Outcomes in people with schizophrenia spectrum disorders are suboptimal with low quality of life, low rates of recovery, substance misuse, higher rates of suicide, violence and legal problems, low educational and vocational attainment, and a significantly reduced life-expectancy of 15-20 year. Schizophrenia imply a large burden of disease with severe impact on patients, their families, the service system and a large economic societal burden. The investigators will include 290 participants age 12-17 years with an early onset psychosis within the following diagnostic classes: schizophrenia spectrum, psychotic depression or drug-induced psychosis. The design is an independent, investigator initiated, pragmatic, randomized clinical trial, with blinded outcome assessment. Participants are randomized 1:1 to OY or TAU. Participants in OY are offered 2 years of specialized intervention (OY) regardless of age, while participants in TAU are switched to adult psychiatry at the age of 18 years. OY builds on the Danish evidenced based intervention for young adults, OPUS, adjusted to meet the specific needs of adolescents: intensified support for caretakers and relatives including siblings; social cognition and interaction treatment; and individual cognitive behavioral case management. OY addresses the specific challenges of psychopharmacologic treatment in youth; supported transition to adult care after OY; school or educational support; and prevention and treatment of substance misuse. The primary endpoint is improved functioning in daily and social life after 24 months. Secondary outcome measures are psychopathology, quality of life, family stress, and retention in treatment and school/employment, and healthcare consumption. The clinical and societal perspective of a large scale implementation is improved prevention of the negative consequences of early-onset psychosis and a reduced burden of severe mental illness.

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.

SUCCEED Africa: Support, Comprehensive Care and Empowerment of People With Psychosocial Disabilities

Although psychotic disorders typically affect less than 1% of the population, they are a significant cause of disability worldwide. Psychotic symptoms such as hallucinations, delusions and suicidal ideation can be profoundly disturbing, and negatively impact daily living. However, the social consequences of psychosis are often even more troubling than the symptoms. For example, people with psychosis have a high risk of experiencing violence, poverty, homelessness, incarceration, and unemployment, among other adverse outcomes. There is a need for a range of accessible, appropriate interventions for people with psychosis to be delivered to those in the most vulnerable situations, including in low-resource settings in sub-Saharan Africa. A systematic review recently carried out as part of the formative research for SUCCEED identified 10 studies evaluating the impact of interventions for people with psychosis in Africa, most of which had a strongly clinical focus. The review concluded that there was a need for further research involving people with lived experience of psychosis in designing and evaluating holistic interventions that meet their diverse needs, within and beyond the health sector. SUCCEED Africa is a six-year Health Research Programme Consortium (RPC) that has brought together people with lived experience of psychosis and people with professional experience (researchers, clinicians) from four African countries (Malawi, Nigeria, Sierra Leone, Zimbabwe) to co-produce a community-based intervention for psychosis, using a Theory of Change-driven approach. The SUCCEED intervention takes the World Health Organisation's (WHO's) CBR Matrix as a point of departure to consider the multifaceted needs of people living with psychosis and other psychosocial disabilities, and how best to meet these needs by mobilising the resources of individuals and families affected, as well as their broader communities. This protocol describes a pilot study in which the SUCCEED intervention will be delivered and evaluated on a small scale, in preparation for a larger multi-country research evaluation using more rigorous methods, including randomised controlled trials in Nigeria and Zimbabwe and observational studies in Malawi and Sierra Leone, respectively. The main outcome of interest is change in subjective quality of life among participants with lived experience of psychosis who are offered the intervention over a four-month follow up period.

PS-Trauma - Development of Trauma Treatment for Patients With Co-morbid Psychotic Disorders and Traumas

Overview: People with psychotic disorders frequently have a history of traumatic events such as neglect, bullying, or physical and sexual abuse. Many experience significant symptoms of post-traumatic stress, but trauma-focused treatment is rarely offered in standard psychiatric care. This pilot study investigates whether two established trauma therapies can be delivered safely and acceptably to young adults with psychotic disorders receiving care in the OPUS early-intervention program. Objectives: The main aim is to evaluate the feasibility and acceptability of two trauma-focused treatments-Prolonged Exposure (PE) and Eye Movement Desensitization and Reprocessing (EMDR)-in patients with psychotic disorders and post-traumatic stress symptoms. The study is not designed to test treatment efficacy but to determine whether a larger randomized controlled trial is practical. Study Design: This is a pilot and feasibility study. Twenty OPUS patients with a diagnosis within the schizophrenia spectrum and clinically relevant PTSD symptoms will be randomly assigned to either PE or EMDR. All participants continue their usual OPUS care while attending weekly trauma-focused therapy sessions. Assessments: At baseline and follow-up, participants complete clinical interviews and questionnaires assessing trauma symptoms, psychotic symptoms, functioning, well-being, recovery experiences, and possible negative effects. Instruments include the PCL-5, CAPS-5, Mini-TALE, PANSS-6, PSP, WHO-5, Brief INSPIRE-O, NEQ, and CSQ. Primary Feasibility Outcomes: Recruitment: At least 80% of the planned sample enrolled within 6 months. Retention: At least 70% completing ≥12 therapy sessions. Acceptability: Participant satisfaction measured with the Client Satisfaction Questionnaire (CSQ). Eligibility: Inclusion: Age ≥18 Diagnosis within the schizophrenia spectrum (ICD-10: F20-F29) PTSD symptom score \>31 on PCL-5 Current OPUS patient Sufficient Danish language skills Exclusion: Substance use that prevents participation (e.g., attending sessions intoxicated) Severe cognitive impairment Recent changes in antipsychotic medication (within 1 month) Risks and Safety: Temporary increases in PTSD symptoms may occur when beginning trauma therapy; this pattern is well documented and typically followed by improvement. Previous studies show no higher risk of serious adverse events among patients with psychosis receiving trauma treatment compared with those who do not. Participants are closely monitored, and the study team works in continuous collaboration with OPUS clinicians. If a participant experiences significant clinical deterioration, the therapy can be paused or stopped, and supportive measures will be provided. Potential Benefits: Participants may experience a reduction in trauma-related symptoms and gain access to a treatment that is not otherwise routinely offered to patients with psychotic disorders. The study may help improve future care for this underserved population. Funding: The study is funded by the Nektar Foundation and conducted at the CORE Research Unit, Mental Health Services Copenhagen.