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

Study Overview
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Brief Summary
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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 284 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.

Official Title
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The OPUS YOUNG Study. The Efficacy of Early Intervention Service Versus Treatment as Usual for Adolescents Aged 12 - 17 With First-episode Psychosis, a Pragmatic Randomized Clinical Trial

Conditions
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Schizophrenia, Schizotypal Disorder, Delusional Disorder, Acute and Transient Psychotic Disorder, Unspecified, Schizoaffective Disorder, Non-Organic Psychosis, Depression Severe, Substance Induced Psychoses

Intervention / Treatment
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* Behavioral: OPUS YOUNG
* Behavioral: Treatment as Usual


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Between 12 and 17 years of age (both inclusive) at trial inclusion. First-episode psychosis within F2 spectrum (F20 schizophrenia, F21 Schizotypal disorder, F22 delusional disorder, F23 acute and transient psychotic disorders, F25 schizoaffective disorders, F28/29 other or un-specified non-organic psychosis) or depression with psychotic symptoms (F32.3, F33.3) or substance-induced psychosis (F1X.5) according to the International Statistical Classification of Diseases and Related Health Problems (ICD-10). Maximum 12 months since first prescription of antipsychotic treatment on the indication psychosis. Speak and understand Danish. Written informed consent from parents or legal caretakers. Participants who reach age 18 years during the trial will be asked to give personal written informed consent to continue their study participation. Exclusion Criteria: A diagnosis of mental retardation of at least moderate severity defined as an intelligence quotient (IQ)of 49 or below (F71, F72, F73 according to the International Statistical Classification of Diseases and Related Health Problems (ICD-10). Currently compulsory admission and/or treatment according to Danish legislation

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: The randomized clinical trial is a parallel, two-arm, superiority trial comparing OPUS YOUNG with TAU for children and adolescents aged 12 - 17 years with a first episode psychosis
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: OPUS YOUNG<br>OPUS YOUNG is a two years out-patients specialized early intervention services for children and adolescents with a first episode psychosis. OPUS YOUNG is characterized by a multidisciplinary team, assertive outreach, tailored cognitive behavioral case management, and low caseload and insensitive psychoeducational family involvement | Behavioral: OPUS YOUNG<br>* OPUS YOUNG is a two year out-patient specialized early intervention service for children and adolescents with a first episode psychosis. The OPUS YOUNG treatment consists of the following elements: modified assertive community treatment, low patients to case manager ratio, cognitive-behavioural case management (CBCM), psycho-educational family treatment including multiple family groups(MFG) and psychoeducational siblings groups, Social Cognition and Interaction Training (SCIT), possible individual Cognitive Behavioural Therapy (CBT) in addition to CBCM, and manual based psychopharmacologic treatment. Additional, special transition support, individual school/employment support, and prevention and treatment of substance abuse.<br>|
| Active Comparator: Treatment as Usual, TAU<br>Treatment as Usual will be carried out by outpatient clinic in Child and Adolescent Mental Health Services (CAMHS). Patients will be offered treatment following national Danish guidelines and local guidelines, provided by a multidisciplinary team, case-management (no defined upper-case load), family support. In general, office visits take place in outpatient clinics. | Behavioral: Treatment as Usual<br>* The patients allocated to TAU will be offered non-manualized treatment following national Danish guidelines and local guidelines. Treatment is provided by a multidisciplinary team and consists of case-management (no defined upper case load), family support and psychoeducation, in addition to psychopharmacological treatment. In some cases, social skills training and CBT may be offered. In general, office visits take place in outpatient clinics.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Personal and Social Performance Scale (PSP) | Change in the global score of social function, measured with Personal and Social Performance Scale (PSP). PSP provides a global score on a scale from 1-100, with lower scores indicating lower social functioning. The global score is based on scores on four subdomains (1. Socially useful activities, 2. Personal and social relationships, 3. Self-care, and 4. Disturbing and aggressive behaviour), rated on a 6-point Likert scale (1=absent to 6=very severe). The scoring of PSP is based on all available information and concerns the patient's daily level of functioning in the family, in school, and during leisure time during the past month. Higher global values mean better social function. Researchers will interview the participants prior to the scoring of PSP using a semi structured interview guide suitable for children and adolescents, developed by the OPUS YOUNG research team. | Last month at baseline (from enrollment), at month 12, at month 24 and at month 30 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Severity of psychotic symptom dimension, SAPS | Scale for Assessing Psychotic Symptoms in Schizophrenia (SAPS), used to assess the phenomenological presentation of psychotic symptoms in schizophrenia, is a rating scale to measure positive symptoms in schizophrenia. The SAPS- scale is split into 4 sub-scales (hallucinations, delusions, bizarre behavior and formal thought disorder) each of which are rated from 0 (absent) to 5 (severe) and for each domain is also given a global symptom severity score by the rater. The Psychotic symptom dimension is the sum of global scores, divided by the number of global scores (range 0-5). The psychotic dimension is composed of scores of hallucination and delusions. Higher score indicates worse level of symptoms. | Last month at baseline (from enrollment), at month 12, at month 24 and at month 30 | 
| Severity of Negative symptom dimension, SANS | Scale for Assessing Negative Symptoms in Schizophrenia (SANS), used to assess the phenomenological presentation of negative symptoms in schizophrenia, is a rating scale to measure negative symptoms in schizophrenia. The SANS scale is divided into five sub-scales (affective flattening, alogia, avolition-apathy, anhedonia-asociality, attention), each of which are rated from 0 (absent) to 5 (severe) and for each domain is also given a global symptom severity score by the rater (global ratings). The Negative symptoms dimension is calculated as the sum of the global scores, divided by the number of global scores (range 0-5). The negative symptom dimension is composed of scores of anhedonia, avolition, affective flattening and alogia. Higher score indicates worse level of symptoms. | Last month at baseline (from enrollment), at month 12, at month 24 and at month 30 | 
| Severity of disorganized symptom dimension | Severity of Disorganized symptom dimension is calculated as the sum of the global scores of formal thought disorder, bizarre and behaviors from Scale for Assessing Psychotic Symptoms in Schizophrenia (SAPS) and the score of inappropriate affects (item within the subscale for affective flattening) in Scale for Assessing Negative Symptoms in Schizophrenia (SANS) (range 0-5).Higher score indicates worse level of symptoms. | Last month at baseline (from enrollment), at month 12, at month 24 and at month 30 | 
| Client satisfaction questionnaire, CSQ | Patients satisfaction with the treatment is measured with the CSQ-scale. CSQ assess global client satisfaction, along with single dimension. The CSQ has eight question-items (quality of service, kind of service, met needs, recommend to a friend, amount of help, deal with problems, overall satisfaction, and come back). Patients respond to those question-items using a 4-point Likert scale. Their responses are scored from 1 to 4, and thus the possible total scores range from 8 to 32. Higher scores indicate greater satisfaction. Self-rapport | Present time at month 12 and at month 24. | 
| Quality of life, - Health Related Quality of Life Questionnaire for Children and Young People and their Parents, KIDSCREEN-10 | The participants perception of their quality of life is assessed using the self-administered questionnaire KIDSCREEN-10. KIDSCREEN-10 contains 10 items: (1) Have you felt fit and well? (2) Have you felt full of energy? (3) Have you felt sad? (4) Have you felt lonely? (5) Have you had enough time for yourself? (6) Have you been able to do the things that you want to do in your free time? (7) Have your parent(s) treated you fairly? (8) Have you had fun with your friends? (9) Have you got on well at school? (10) Have you been able to pay attention? Participants respond to those question/items using a 5-point response scale. Answer categories item 1 and 9: not at all-slightly-moderately-very-extremely; all other items: never-seldom-quite often-very often-always. Responses are coded so that higher values indicate better QoL. A low score indicates a poor QOL, and a high score is indicative of a better QOL. | Last week at baseline (from enrollment), at month 12, at month 24 and at month 30 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Specialized early intervention, Early onset psychosis, Children and adolescents, Recovery and resilience, Cost-effectiveness