Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12614000009617
Ethics application status
Approved
Date submitted
24/10/2013
Date registered
3/01/2014
Date last updated
30/10/2023
Date data sharing statement initially provided
1/11/2018
Date results provided
30/10/2023
Type of registration
Retrospectively registered

Titles & IDs
Public title
The Horyzons trial: Moderated Online Social Therapy for Maintenance of Treatment Effects from Specialised First Episode Psychosis Services
Scientific title
A randomised controlled trial evaluating the effects of Horyzons, a moderated online social therapy, on social functioning in young people with first episode psychosis.
Secondary ID [1] 283143 0
Nil
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
First episode psychosis 290001 0
Condition category
Condition code
Mental Health 290385 290385 0 0
Schizophrenia
Mental Health 290786 290786 0 0
Psychosis and personality disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The intervention for investigation is a world-first on-line system entitled Horyzons, designed with the purpose of maintaining the clinical benefits of early intervention in young people who have experienced first episode psychosis (FEP).

Horyzons has been developed by a multidisciplinary team of clinical psychologists, computer programmers, health informatics experts, web and graphic designers, and professional writers. In accordance with international recommendations, the online system has been developed iteratively over a 30-month period following participatory design principles through a process of regular feedback and testing with focus groups of stakeholders (i.e. FEP patients and clinicians). Horyzons includes fully functional versions for computer and internet-enabled mobile devices.

The Horyzons system comprises a platform for the delivery of a range of evidence-based and interactive psychosocial interventions which are enhanced by a moderated on-line social networking environment. Specifically, Horyzons integrates: i) peer-to-peer on-line social networking; ii) individually tailored interactive psychosocial interventions; and (iii) expert and peer moderation.

The psychosocial interventions, based on principles of Positive Psychology, CBT for coping and Mindfulness, psychoeducation target key risk factors and salient domains in the early recovery process including: (a) vocational recovery, (b) early warning signs of relapse (EWS), (c) depression, (d) social anxiety, (e) personal strengths, and (f) substance abuse.

Horyzons is a User Driven system. There is no minimum requirement for using Horyzons and participants can use which ever parts of the system they choose. Expert moderators will help users make the most of the system and encourage a positive, supportive and safe experience. To improve adherence with and minimise attrition from Horyzons, moderation will be informed by self-determination theory (SDT) which is concerned with supporting our natural or intrinsic tendencies to behave in effective and healthy ways. All user activity will be captured through the Horyzons platform and this data will form part of the analysis.

Patients with FEP randomised to the intervention group will receive access to Horyzons for 18 months from randomisation plus standard treatment at discharge. This will be the first study to examine whether an innovative online intervention is an effective strategy for the maintenance of specialised treatment effects in FEP.
Intervention code [1] 287875 0
Behaviour
Comparator / control treatment
Participants randomized to Standard Treatment will receive standard treatment following discharge from the Early Psychosis Prevention and Intervention Centre (EPPIC) program.

EPPIC is a world-leading specialist FEP program in Melbourne or 15-25 year olds. It was established in 1992 and treats 250 FEP patients per year12. EPPIC is staffed by 2 psychiatrists, 3 psychiatry registrars, and 18 case managers. Patients are regularly reviewed by the treating
psychiatrists, and therapists deliver weekly psychological interventions and case management following early intervention guidelines for FEP. All patients
have access to after-hours crisis care, an assertive outreach team, a group program and inpatient treatment when needed. EPPIC provides 18 months to 2 years of specialised care after which patients are transferred to standard treatment.

Standard treatment will consist of a range of treatment options including follow-up by a GP, private psychiatrist, or adult area mental health service which deliver multidisciplinary psychiatric care including medical follow-up, case management and acute psychiatric care as appropriate. Additionally, Standard Treatment participants will be provided with a booklet containing practical information on existing e-mental health resources (i.e. Moodgym, e-headspace, Reach-out, and OYHCP Client’s hub).
Control group
Active

Outcomes
Primary outcome [1] 290409 0
Social functioning as measured by the Personal and Social Performance Scale (PSP) and the First Episode Social Functioning Scale (PESFS).

Social functioning will be measured via the Personal and Social Performance Scale (PSP) and the First Episode Social Functioning scale (FESFS). The PSP is a 100-point single-item rating scale derived from Social and Occupational Functioning Assessment Scale (SOFAS) and developed specifically to assess social functioning in schizophrenia. Ratings are based on the rater’s evaluation of patient’s functioning in four main areas: 1) socially useful activities; 2) personal and social relationships; 3) self-care; and 4) disturbing and aggressive behaviours. Each domain is assessed on a six-category severity scale ranging from absent to very severe. The PSP improves on the SOFAS by including clear operational instructions on ratings severity of disability, specifying areas to be rated, and removing psychopathological aspects.

The First Episode Social Functioning scale (FESFS) has been specifically developed to measure social functioning in young people with psychosis in the 21st century. The FESFS was designed to assess multiple domains of social functioning reflecting as closely as possible the contemporary social reality of youth and young adults with psychosis. The following FESFS subscales have been selected to be used in this study based on their psychometric properties and relevance to the Horyzons intervention: friends and activities (6 items; internal consistency =0.80); independent living skills (4 items; internal consistency =0.81); interacting with people (4 items; internal consistency =0.80); and intimacy (5 items; internal consistency =0.75). Principal component factor analysis provided support to the structure of the FESFS and independence of its subscales. Finally, the selected FESFS subscales have shown to correlate with other measures of social functioning, to be independent of psychotic symptoms, and to be sensitive to treatment effects.
Timepoint [1] 290409 0
18 months after randomisation
Secondary outcome [1] 304440 0
Positive and negative psychotic symptoms as measured by the The Positive and Negative Syndrome Scale (PANSS).
Timepoint [1] 304440 0
6, 12 and 18 months after randomisation
Secondary outcome [2] 304441 0
Depression as measured by the Calgary Depression Scale for schizophrenia (CDSS), a 9-item structured interview scale developed to assess depression in schizophrenia. The CDSS is considered to be the most reliable and valid instrument for assessing depressive symptoms in schizophrenia. It has shown to effectively discriminate depressive symptoms from other schizophrenia symptoms and demonstrated high diagnostic sensitivity and specificity.
Timepoint [2] 304441 0
6, 12 and 18 months after randomisation
Secondary outcome [3] 304442 0
Psychological wellbeing as measured by the 42-item version of the Scales of Psychological Wellbeing (SPWB). The SPWB was developed to measure psychological wellbeing from a multidimensional perspective. It includes 6 subscales (and a total score) measuring 6 constructs of positive psychological functioning: environmental mastery, personal growth, purpose in life, autonomy, self-acceptance, and positive relations with others. The SPWB dimensions were informed by the most significant frameworks of positive functioning proposed by previous psychology research104. Items are measured on a 7-point Likert scale ranging from 1 (strongly disagree) to 6 (strongly agree). The SPWB has demonstrated good internal consistency for the total score and each of the subscales. Confirmatory factor analysis have supported the theoretical 6-factor model of wellbeing. It was been validated in many different samples and has been previously used in psychosis research.
Timepoint [3] 304442 0
6, 12 and 18 months after randomisation
Secondary outcome [4] 304443 0
Anxiety as measured by the Depression Anxiety and Stress Scale (DASS) and the Social Interaction Anxiety Scale (SIAS). The DASS is a 42-item, self-report questionnaire that includes three scales measuring depression, anxiety and stress. Each of the three scales contains 14 items measured on 4-point severity/frequency scales. For the purposes of this study the Anxiety and Stress Scales will be used. The Anxiety scale assesses autonomic arousal, skeletal muscle effects, situational anxiety, and subjective experience of anxiety. The Stress scale assesses non-specific arousal including difficulty relaxing, nervous arousal, and being easily upset/agitated, irritable/over-reactive and impatient. All the DASS scales have demonstrated high internal consistency, convergent and discriminant validity and sensitivity to treatment effects. The DASS has been used in First Episode Psychosis and at-risk mental state for psychosis. Social anxiety will be measured by means of the Social Interaction Anxiety Scale (SIAS). The SIAS is a 20-item self-report measure assessing anxiety in interpersonal encounters (distress when meeting and talking with other people). Items are rated on 5-point likert scale ranging from 0 (not at all characteristic or true of me) to 5 (extremely characteristic or true of me). The SIAS has has shown excellent psychometric properties and received extensive validation. The SIAS has been used in psychosis research and has shown to effectively discriminate between social anxiety, other anxiety disorders and community samples.
Timepoint [4] 304443 0
6, 12 and 18 months after randomisation
Secondary outcome [5] 304444 0
Social support and social isolation as measured by Medical Outcomes Study: Social Support Survey (MOS-SSS) and the UCLA Loneliness Scale (Version 3).

The MOS-SSS is a 19-item multidimensional self-report measure of perceived availability of functional social support. It includes four subscales that represent multiple dimensions of functional support: emotional/information, tangible, affectionate and positive social interaction. Each item is rated on a 5-point Likert scale ranging from ‘None of the time’ to ‘All the time’. The development of the MOS-SSS was informed by functional support theories of social relationships and consistent evidence that perceived social support shows stronger associations with health and wellbeing than received social support. The MOS-SSS has shown strong psychometric properties including high internal consistency (0.91), test-retest reliability and sensitivity to change. It has established reliability and validity across a wide range of languages and cultures.

The UCLA Loneliness Scale (Version 3) is an extensively used, 20-item, unidimensional scale designed to measure state loneliness and feelings of social dissatisfaction. Items are measured on a 4-point Likert scale ranging from 1 (never) to 4 (always). It has demonstrated high internal consistency (ranging from 0.89 to 0.94) and test-retest reliability (r = 0.73) across different samples.
Timepoint [5] 304444 0
6, 12 and 18 months after randomisation.
Secondary outcome [6] 304445 0
Quality of life (QoL) as measured by the AQoL 8D. The AQoL 8D is a 35-item self-report questionnaire measuring 8 dimensions of QoL: independent living, relationships, mental health, coping, pain, senses, self-worth and happiness. It has demonstrated strong psychometric properties and has been extensively used in psychosis research.
Timepoint [6] 304445 0
6, 12 and 18 months after randomisation
Secondary outcome [7] 304446 0
Satisfaction with life as measured by Satisfaction With Life Scale (SWLS).

The SWLS was developed to measure global life satisfaction independently of related constructs such as positive affect or loneliness. It has demonstrated strong psychometric properties including high internal consistency, temporal reliability and construct validity. The SWLS includes 5 items measured on a 7-point Likert scale ranging from 1 (strongly disagree) to 7 (strongly agree). This scale has been previously used in psychosis research.
Timepoint [7] 304446 0
6, 12 and 18 month after randomisation.
Secondary outcome [8] 304447 0
Self-esteem as measured by the Self-Esteem Rating Scale-Short Form (SERS-SF).

The SERF-SF was derived from the self-esteem rating scale and comprises 20 items rated on a seven-point Likert scale measuring positive self-esteem (PSE, 10 items) and negative self-esteem (NSE, 10 items). The importance of the distinction between PSE and NSE has been highlighted by recent studies showing that patients with psychosis could concurrently have high ratings on both self-esteem domains, making the use of a global score difficult to interpret. The SERF-SF has demonstrated good reliability (alpha ranging from 0.84 to 0.94 for the positive and negative scales), validity and responsiveness to treatment effects in schizophrenia and FEP.
Timepoint [8] 304447 0
6, 12 and 18 months after randomisation
Secondary outcome [9] 304448 0
Empowerment and self-efficacy as measured by the Mental Health Confidence Scale (MHCS).

The MHCS is a 16-item scale designed to assess intrapersonal aspects of empowerment and self-efficacy. It includes three subscales measuring optimism, coping and advocacy. Questions focus on patients’ global confidence in their coping skills across a range of situations (e.g. “How confident are you right now that you can: ‘set goals for yourself’, ‘deal with symptoms related to one’s mental illness diagnosis’ etc.). Items are rated on a 6-point Likert scale ranging from 1 (very nonconfident) to 6 (very confident). A recent review on empowerment measures recommended the MHCS as the preferred instrument to assess empowerment in psychosis because of its clinical usefulness and sound psychometric properties. In addition, the MHCS has been recommended for the evaluation of treatment effects of peer support groups and psychological interventions.
Timepoint [9] 304448 0
6, 12 and 18 months after randomisation.
Secondary outcome [10] 304449 0
Physical health as measured by waist circumference.

Waist circumference has been recommended as a simple and appropriate method to measure body fatness, which also captures information on abdominal fat distribution. It has been shown to be more is more sensitive to changes in energy balance than the Body Mass Index (BMI). In addition, it has been suggested that waist circumference is less affected than BMI by variation in lean mass.
Timepoint [10] 304449 0
6, 12 and 18 months after randomisation
Secondary outcome [11] 304450 0
Substance use as measured by means of the Alcohol, Smoking and Substance Involvement Screening Test (ASSIST version 3.1).

The ASSIST (version 3.1) was developed by the World Health Organization (WHO) as a screening tool for 10 psychoactive substances (tobacco, alcohol, cannabis, cocaine, amphetamine-type stimulants, benzodiazepines, hallucinogens, inhalants, opioids and ‘other’ drugs). It consists of 8 interviewer-administered items measuring lifetime and recent (past 3 months) substance use, abuse and dependence. The ASSIST has demonstrated sound psychometric properties including good internal consistency as well as construct, concurrent and discriminant validity on all substances. A recent study has shown the ASSIST to be a reliable and valid measure of substance use in first-episode psychosis.
Timepoint [11] 304450 0
6, 12 and 18 months after randomisation.
Secondary outcome [12] 304451 0
Vocational status as measured by employment and/or education status.
Timepoint [12] 304451 0
6, 12 and 18 months after randomisation
Secondary outcome [13] 304452 0
Cost-effectiveness as measured by the AQoL 8D, which allows for the calculation of Quality-Adjusted Life Years (QALYs). QALYs are a generic health outcome measure preferred for use in economic evaluation since value for money judgements can be made using varying thresholds of willingness to pay for gains in QALYs (e.g. $50,000 per QALY gain).

The actual cost of HORYZONS will be determined using information from the research team and provider records including interviews with key budgetary personnel to ensure all costs associated with the intervention have been captured. A Resource Use Questionnaire (RUQ) will be used to determine the broader resource use of participants. The questionnaire will include health care and welfare services as well as education and productivity associated with caregivers. The costs of consulting health professionals will be calculated using published prices for medical and allied health costs.
Timepoint [13] 304452 0
18 months after randomisation
Secondary outcome [14] 353514 0
Hospital admissions due to psychotic symptoms and mental health issues. This will be measured by self-report in the Resource Use Questionnaire and by data linkage to state based hospital admission data.
Timepoint [14] 353514 0
Continuous over 18 months.

Eligibility
Key inclusion criteria
Inclusion criteria for the study will be:
(i) a first episode of a DSM-IV psychotic disorder or mood disorder with psychotic features
(ii) aged 16-27 years inclusive
(iii) less than or equal to 6 months treatment with an antipsychotic medication prior to registration with EPPIC
(iv) remission of positive symptoms of psychosis*
(v) less than or equal to 3 months to the due date of discharge from EPPIC
(vi) low aggressiveness**
(vii) moderate or lower suicidal risk***
(viii) able to nominate an emergency contact

*Remission of positive symptoms of psychosis is defined as 4 weeks or more of scores of 3 (mild) or below on the Positive and Negative Syndrome Scale (PANSS) items:
(i) conceptual disorganization (P2);
(ii) unusual thought content (G9);
score of 4 or below with no functional impairment on PANSS items:
(iii) hallucinatory behaviour (P3);
(iv) delusions (P1);

**Low aggressiveness is defined as a score of 3 or below on the poor impulse control item of the PANSS for the month prior to study entry

***Moderate or lower suicidal risk is defined as a score of 4 or below on the Brief Psychiatric Rating Scale - expanded version (BPRS) suicidality subscale for the month preceding study entry.
Minimum age
16 Years
Maximum age
27 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria for the study will be:
(i) intellectual disability*
(ii) inability to converse in, or read English.
(iii)DSM-IV diagnosis of antisocial personality disorder (ASPD)
(iv) DSM-IV diagnosis of borderline personality disorder (BPD) with the additional criteria that the BPD features cause interpersonal difficulties in the treatment environment

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Treatment allocation concealment will be achieved by using a password protected computer program, implemented by an
independent member of the Orygen Youth Health Research Centre statistician team.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Participants will be assigned to the treatment condition by simple randomisation using a randomisation table created by computer software.

Randomisation will be stratified by site (Sunshine and Parkville).
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Other design features
Phase
Not Applicable
Type of endpoint/s
Statistical methods / analysis
Sample size: The primary outcome is change in social functioning at 18 months follow-up. In two previously published large trials on the long-term effectiveness of specialised early intervention vs. standard care the effect size of the intervention effects were reported to be 0.5 for functional outcomes. If we assume that alpha is set at 0.05 and power (1-B) at 0.90, then a sample size of 70 is required for each of the two groups (Total n = 140) to detect medium effect sizes (0.5; Cohen's d). For the second outcome measure of relapse rates at 18 months follow-up, there will be 80% power to detect an improvement in the rate of relapse of at least 20% in the FU-ST+Horyzons, assuming relapse rate in the FU-ST of 45% (consistent with our previously published study). Our recruitment time frame of 28 months realistically allows us to recruit a total of 196 patients, providing an adequate buffer to accommodate attrition following randomisation of up to 28%.

Statistical analysis: Primary analyses will be undertaken on an intention-to-treat basis. Mixed-model repeated measures (MMRM) analyses will be used to analyse change in continuous outcome scores (i.e. social functioning and secondary outcome measures) because it has been demonstrated to be superior to the LOCF (last observation carried forward) method for handling missing data missing data in longitudinal designs. The within-groups factor will be time (baseline, 6, 12, and 18 months) and group will serve as the between-subjects factor (FU-ST vs. FU-ST+Horyzons).

Additional analyses will use multiple imputation to assess the robustness of the findings to the choice of method for handling missing data. Ecological momentary assessment will be analysed using a multilevel structural equation modelling (MSEM) framework. Differential rate of hospital admissions will be analyzed using multilevel logistic regression. Time to hospital admissions will be assessed by survival analysis (using either proportional hazard or accelerated life-time models). Additional comparisons between treatment groups based on completers-only analyses will be conducted. Analyses will be undertaken in accordance with ICH 9 guidelines including a full analysis as well as per protocol set. The per protocol sample will be defined based on receiving a pre-specified minimal exposure to the online intervention (i.e., more than 16 logins over the 18-month intervention period).

Economic Evaluation will comprise a cost-consequences analysis whereby the incremental costs of the intervention will be compared to the full spectrum of outcomes included in the study. This means that a series of cost-effectiveness ratios will be determined rather than just one. The inclusion of the AQoL8D will also enable a cost-utility analysis to be undertaken, thereby allowing practical judgements regarding value for money credentials of the intervention to be made. The evaluation will first measure and value any change to the use of health care resources over the period of the study between the two arms of the trial and then compare any additional costs to the additional outcomes achieved. Standardised economic evaluation techniques including incremental analysis of mean differences and bootstrapping to determine confidence intervals will be used in the evaluation. The lifetime and population cost-effectiveness of the intervention will be determined using modelling techniques refined by CI-Mihalopoulos.
Update Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
1/10/2013
Actual
29/11/2013
Date of last participant enrolment
Anticipated
31/12/2015
Actual
15/03/2017
Date of last data collection
Anticipated
30/09/2018
Actual
30/07/2018
Sample size
Target
196
Accrual to date
Final
170
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment postcode(s) [1] 7322 0
3052 - Parkville
Recruitment postcode(s) [2] 22051 0
3020 - Sunshine

Funding & Sponsors
Funding source category [1] 288142 0
Government body
Name [1] 288142 0
Victorian Government Mental Illness Research Fund
Country [1] 288142 0
Australia
Primary sponsor type
Charities/Societies/Foundations
Name
Orygen, The National Centre of Excellence in Youth Mental Health
Address
35 Poplar Rd
Parkville, VIC, 3052
Country
Australia
Secondary sponsor category [1] 286859 0
None
Name [1] 286859 0
Address [1] 286859 0
Country [1] 286859 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 290055 0
Melbourne Health Human Research Ethics Committee
Ethics committee address [1] 290055 0
Ethics committee country [1] 290055 0
Australia
Date submitted for ethics approval [1] 290055 0
Approval date [1] 290055 0
30/07/2013
Ethics approval number [1] 290055 0
2013.146

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 42666 0
A/Prof Mario Alvarez
Address 42666 0
Orygen, The National Centre of Excellence in Youth Mental Health, Locked Bag 10, Parkville, VIC 3052, Australia
Country 42666 0
Australia
Phone 42666 0
+61 1300 679 436
Fax 42666 0
Email 42666 0
[email protected]
Contact person for public queries
Name 42667 0
Daniela Cagliarini
Address 42667 0
Orygen, The National Centre of Excellence in Youth Mental Health, Locked Bag 10, Parkville, VIC 3052, Australia
Country 42667 0
Australia
Phone 42667 0
+61 408607919
Fax 42667 0
Email 42667 0
[email protected]
Contact person for scientific queries
Name 42668 0
Mario Alvarez
Address 42668 0
Orygen, The National Centre of Excellence in Youth Mental Health, Locked Bag 10, Parkville, VIC 3052, Australia
Country 42668 0
Australia
Phone 42668 0
+61 1300 679 436
Fax 42668 0
Email 42668 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
All of the individual trial-related participant data collected during the trial, after de-identification.
When will data be available (start and end dates)?
Data will be available immediately following publication of main study outcomes for an indefinite time.
Available to whom?
Data will potentially be available to researchers from not-for profit organisations, commercial organisations or other based in any location. All data requests will be considered by the data custodian and the primary sponsor on a case-by-case basis. Requests must include a methodologically sound proposal. Specific conditions of use may apply and will be specified in a data sharing agreement (or similar) that the requester must agree to before access is granted. For further information, see Orygen data sharing policy.
Available for what types of analyses?
Any approved protocol, IPD meta-analysis or systematic review. Assessed on a case-by-case basis.
How or where can data be obtained?
Initial requests can be made by contacting the Research Office at Orygen ([email protected]).


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
20787Study protocol  [email protected]
20788Informed consent form  [email protected]



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseBlended digital and face-to-face care for first-episode psychosis treatment in young people: Qualitative study.2020https://dx.doi.org/10.2196/18990
EmbaseCharacterizing Use of a Multicomponent Digital Intervention to Predict Treatment Outcomes in First-Episode Psychosis: Cluster Analysis.2022https://dx.doi.org/10.2196/29211
EmbaseUnderstanding What Drives Long-term Engagement in Digital Mental Health Interventions: Secondary Causal Analysis of the Relationship Between Social Networking and Therapy Engagement.2023https://dx.doi.org/10.2196/44812
N.B. These documents automatically identified may not have been verified by the study sponsor.