Clinical trial NCT04916626: The OPUS YOUNG Trial. Early Intervention Versus Treatment as Usual for Adolescents With First-episode Psychosis
Official title: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Schizophrenia
Schizotypal Disorder
Delusional Disorder
Acute and Transient Psychotic Disorder, Unspecified
Schizoaffective Disorder
Non-Organic Psychosis
Depression Severe
Substance Induced Psychoses
Keywords: Specialized early intervention
Early onset psychosis
Children and adolescents
Recovery and resilience
Cost-effectiveness
Cross-sectional
Lead sponsor: Mental Health Services in the Capital Region, Denmark
Sponsor class: OTHER
First posted: 2021-06-07
Enrollment: 284
Sex: ALL
Minimum age (years): 12
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: The overarching purpose of the OPUS YOUNG trial is to improve the treatment and outcome of first-episode psychosis (FEP) in children and adolescents. We will address this ambition by testing the hypothesis, that Early Intervention Services (EIS) is superior compared to standard care in the treatment of children and adolescents below age 18 years with first-episode psychosis. The hypothesis is based on extrapolation of research showing that EIS is superior to standard care in the treatment of adults with first-episode psychosis with regards to symptom reduction, function improvement, adherence to treatment, lower hospitalization risk, improved recovery, and higher cost-effectiveness. However, no trials have investigated EIS in samples of patients below age 18 years. We will compare the efficacy and cost-effectiveness of EIS to treatment as usual (TAU) in adolescents aged 12-17 years (both inclusive) with first-episode psychosis. We will build on a Danish evidence-based intervention developed for young adults (OPUS) and adjust the concept to meet the specific needs of children and adolescents with early onset psychosis (OPUS YOUNG). The OPUS treatment is a coordinated and integrated manualized multimodal treatment building on three core elements: modified assertive community treatment with a low patient-case manager ratio; psychoeducational family intervention; and social skills training (SST). In OPUS YOUNG we will adjust the OPUS program to fit our younger age group by: 1) intensifying the support for caretakers and relatives including siblings, 2) instead of SST we are introducing social cognition and interaction treatment (SCIT), 3) providing individual cognitive behavioural case management (CBCM) to all participants and cognitive behavioural therapy (CBT) when needed, 4) addressing the specific challenges of psychopharmacologic treatment in adolescents by providing a treatment algorithm, 5) providing intensive supported transition of care (when patients approach transition to adult mental health services), 6) providing individualized school support, and 7) providing integrated prevention and treatment of substance misuse. Based on sample size estimation, we will include a minimum of 284 participants (maximum 304) and randomize them 1:1 to a two-year intervention of OPUS YOUNG versus TAU. We will conduct blinded assessment of treatment effects after 12 months and at treatment endpoint at 24 months. A further follow-up assessment will be performed to evaluate the sustainability of the intervention effects at six months after transition from OPUS YOUNG to TAU. Our primary outcome at treatment endpoint will be social function measured with Personal and Social Performance Scale (PSP). Secondary key outcomes measures are positive and negative symptoms, client satisfaction, and health related quality of life. Further outcomes are the broader psychopathology, cognitive functioning, social cognition, self-efficacy, experience of service, treatment alliance and adherence, the use of pharmacotherapy, school adherence, family burden, siblings' perceived stress, substance misuse, adverse treatment effects, and health economic measures.

Eligibility criteria: Inclusion Criteria:

1. Between 12 and 17 years of age (both inclusive) at trial inclusion.
2. 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).
3. Maximum 12 months since first prescription of antipsychotic treatment on the indication psychosis.
4. Speak and understand Danish.
5. 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:

1. 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).
2. Currently compulsory admission and/or treatment according to Danish legislation

Primary outcomes:
measure: Personal and Social Performance Scale (PSP)
timeFrame: Last month at baseline (from enrollment), at month 12, at month 24 and at month 30
Secondary outcomes:
measure: Severity of psychotic symptom dimension, SAPS
timeFrame: Last month at baseline (from enrollment), at month 12, at month 24 and at month 30
measure: Severity of Negative symptom dimension, SANS
timeFrame: Last month at baseline (from enrollment), at month 12, at month 24 and at month 30
measure: Severity of disorganized symptom dimension
timeFrame: Last month at baseline (from enrollment), at month 12, at month 24 and at month 30
measure: Client satisfaction questionnaire, CSQ
timeFrame: Present time at month 12 and at month 24.
measure: Quality of life, - Health Related Quality of Life Questionnaire for Children and Young People and their Parents, KIDSCREEN-10
timeFrame: Last week at baseline (from enrollment), at month 12, at month 24 and at month 30
Other outcomes:
measure: Registration of multiaxial diagnostics, Schedule for affective disorders and schizophrenia for school-aged children (6-18 years) (K-SADS-PL), present and lifetime
timeFrame: Present and lifetime at baseline (from enrollment), at month 12 and at month 24
measure: Hallucinations, Experiences of thought disorder and Delusions, Schedules for Clinical Assessment in Neuropsychiatry (SCAN 2.1)
timeFrame: Present and lifetime at baseline (from enrollment), at month 12 and at month 24
measure: Manic symptoms, (YMRS)
timeFrame: Last 2 days at baseline (from enrollment), at month 12, at month 24 and at month 30
measure: Depressions, Hamilton-6, (HAM-6)
timeFrame: Last 3 days at baseline (from enrollment), at month 12, at month 24 and at month 30
measure: Psychotic symptoms, Scale for Assessing Psychotic Symptoms in Schizophrenia (SAPS)
timeFrame: Last month at baseline (from enrollment), at month 12, at month 24 and at month 30
measure: Negative symptoms, Scale for Assessing Negative Symptoms in Schizophrenia (SANS)
timeFrame: Last month at baseline (from enrollment), at month 12, at month 24 and at month 30
measure: Global psychopathology, severity, The Clinical Impression Scale-Severity (CGI-S)
timeFrame: Present at baseline (from enrollment), at month 12, at month 24 and at month 30
measure: Global psychopathology, Improvement, The Clinical Global Impression Scale - Improvement (CGI-I)
timeFrame: Last year at month 12, at month 24 and at month 30
measure: Suicidal behavior
timeFrame: Present and lifetime at baseline (from enrollment), at month 12, at month 24 and at month 30
measure: Changes in global cognitive functioning, Brief Assessment of Cognition in Schizophrenia (BACS)
timeFrame: Present time at baseline (from enrollment) and at month 24
measure: Changes in social cognition, Hinting Task
timeFrame: Present time (from enrollment) and at month 24
measure: Changes in social cognition, EIMT
timeFrame: Present time (from enrollment) and at month 24
measure: General self-efficacy (GSE) (patients)
timeFrame: Present time (from enrollment), at month 12, at month 24 and at month 30
measure: Treatment alliance Working Alliance Inventory scale (WAI)
timeFrame: Last month at month 12, at month 24 and at month 30
measure: Negative effects of psychological treatment questionnaire (NEQ)
timeFrame: Last 2 years at month 24
measure: School adherence
timeFrame: Last 3 month at baseline (from enrollment), at month 12, at month 24 and at month 30
measure: Quality-adjusted life year, European Quality of Life (EuroQol) 5-Dimension 5-Level (EQ 5D - 5L) Questionnaire General Health Status Score
timeFrame: Present time at baseline (from enrollment), at month 12, at month 24 and at month 30
measure: Children health, The Child Health Utility (CHU9D)
timeFrame: Present time at baseline (from enrollment), at month 12, at month 24 and at month 30
measure: Substance abuse, Timeline Follow Back, Trivsel og effekt monitorering (TEM)
timeFrame: Last 4 weeks at baseline (from enrollment), at month 12, at month 24 and at month 30
measure: Medication side-effects, (Danish scale for medication side-effects) Bivirkningsskala Skala Til Registering af Uønskede Virkninger af Psykofarmaka, UKU.
timeFrame: Last 3 days at baseline (from enrollment), at month 12, at month 24 and at month 30
measure: Self-reported use of antipsychotic medication
timeFrame: Last month at baseline (from enrollment), at month 12, at month 24 and at month 30
measure: Executive Function, Behavior Rating Inventory of Executive, 2. edition (BRIEF-2), parent reported questionnaire.
timeFrame: Last six month at baseline (from enrollment), at month 12, at month 24 and at month 30
measure: Parental stress (PSS) parent reported questionnaire.
timeFrame: Present and lifetime at baseline (from enrollment), at month 12, at month 24 and at month 30
measure: Family function (FAD)
timeFrame: Present time at baseline (from enrollment), at month 24 and at month 30
measure: General self-efficacy (GSE) parent-reported questionnaire.
timeFrame: Present time (from enrollment), at month 12, at month 24 and at month 30
measure: The Client satisfaction questionnaire (CSQ). Parent-reported questionnaire.
timeFrame: Present time at month 12 and at month 24
measure: Negative effects of psychological treatment (NEQ). Parent-reported questionnaire.
timeFrame: Last 2 years at month 24
measure: Use of psychopharmacological treatment
timeFrame: From the participant enters the study to month 30
measure: Register-based information (others)
timeFrame: At 30 months (6 months follow-up after end-of-trial)
measure: Electrocardiogram (ECG), standard leads
timeFrame: Present and at baseline (from enrollment), at month 12, at month 24 and at month 30
measure: Personal and Social Performance Scale (PSP), subdomains
timeFrame: Last month at baseline (from enrollment), at month 12, at month 24 and at month 30
measure: Use of health care services
timeFrame: Last month at baseline (from enrollment), at month 12, at month 24 and at month 30
measure: Triglycerides
timeFrame: Present at baseline (from enrollment), at month 12, at month 24 and at month 30
measure: Total cholesterol
timeFrame: Present at baseline (from enrollment), at month 12, at month 24 and at month 30
measure: Low density lipoprotein (LDL)
timeFrame: Present at baseline (from enrollment), at month 12, at month 24 and at month 30
measure: Very-low-density lipoprotein (VLDL)
timeFrame: Present at baseline (from enrollment), at month 12, at month 24 and at month 30
measure: High density lipoprotein, (HDL)
timeFrame: Present at baseline (from enrollment), at month 12, at month 24 and at month 30
measure: Glucose values
timeFrame: Present at baseline (from enrollment), at month 12, at month 24 and at month 30
measure: Determination of prolactin
timeFrame: Present at baseline (from enrollment), at month 12, at month 24 and at month 30
measure: Haemoglobin
timeFrame: Present at baseline (from enrollment), at month 12, at month 24 and at month 30
measure: Leukocyte cell count (and differential count)
timeFrame: Present at baseline (from enrollment), at month 12, at month 24 and at month 30
measure: Thrombocyte cell count
timeFrame: Present at baseline (from enrollment), at month 12, at month 24 and at month 30
measure: Sodium (Na)
timeFrame: Present at baseline (from enrollment), at month 12, at month 24 and at month 30
measure: Potassium (Ka)
timeFrame: Present at baseline (from enrollment), at month 12, at month 24 and at month 30
measure: Creatinine
timeFrame: Present at baseline (from enrollment), at month 12, at month 24 and at month 30
measure: Aspartate transaminase, (ASAT)
timeFrame: Present at baseline (from enrollment), at month 12, at month 24 and at month 30
measure: Alkaline phosphatases;
timeFrame: Present at baseline (from enrollment), at month 12, at month 24 and at month 30
measure: Thyroid-stimulating hormone (TSH)
timeFrame: Present at baseline (from enrollment), at month 12, at month 24 and at month 30
measure: Vitamin D
timeFrame: Present at baseline (from enrollment), at month 12, at month 24 and at month 30
Locations:
city: Hellerup
country: Denmark
facility: Mental Health Services in the Capital Region, Denmark
Study officials:
affiliation: Mental Health Services in the Capital Region, Denmark
name: Anne K Pagsberg, PhD
role: PRINCIPAL_INVESTIGATOR
References: