Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12624000234516
Ethics application status
Approved
Date submitted
13/11/2023
Date registered
11/03/2024
Date last updated
21/07/2024
Date data sharing statement initially provided
11/03/2024
Type of registration
Prospectively registered

Titles & IDs
Public title
Virtual Reality Integrated Social Recovery therapy for Young People with Early Psychosis
Scientific title
Virtual Reality therapy for social cognition and functioning in young people with early psychosis. User-centred design, effectiveness and implementation
Secondary ID [1] 310326 0
Nil known
Universal Trial Number (UTN)
Trial acronym
VISOR
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Psychosis 331046 0
Ultra high risk for psychosis 331047 0
impairment in social cognition 331048 0
Impairment in social functioning 331049 0
Psychotic spectrum disorders 332288 0
Condition category
Condition code
Mental Health 327841 327841 0 0
Psychosis and personality disorders
Mental Health 327842 327842 0 0
Schizophrenia
Mental Health 327843 327843 0 0
Anxiety

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The proposed intervention is an exposure-based cognitive behavioural therapy adapted for delivery via virtual reality to support social functioning and social cognition in young people recovering from psychosis. The interventional condition within the study is the second version (VR-CBT 2.0) of a previously designed version that has been piloted with young people in a previous related project. In this project, six youth advisors aged 16-30 with lived experience of psychotic symptoms and social challenges were recruited to participate in six online group workshops (2 hours each) and one individual session (14 hours total) over six months. VR-CBT 2.0 will be developed following a user centred design process with a group of lived experience experts as an enhancement to our original version. As part of the intervention, participants will be offered 12 sessions (60 minutes), up to 2 per week, over a maximum of 3-months post baseline. VR-CBT 2.0 will include social cognitive interventions embedded in virtual social environments targeting all four key social cognition domains (1) Emotion recognition (2) Theory of mind, (3) Social perception/knowledge and (4) Attributional biases.

VR-CBT 1.0 & 2.0 will be delivered via virtual reality where the participant will wear the VR headset while the VR clinician will speak to them through the headset and voice some of the avatars within the virtual environment to support young people in developing their social and cognitive functioning skills. Meta Quest 2 headsets will be used to deliver the intervention. The clinical intervention will be administered in one-on-one face-to-face appointments lasting 1-hour. Clinical psychologists who have been trained in delivering the intervention via virtual reality will administer the clinical intervention.
Intervention code [1] 327382 0
Treatment: Other
Comparator / control treatment

The original version (VR-CBT 1.0) of an exposure-based VR-CBT intervention that does not include the additional focus on the four domains of social cognition. Participants will be offered 12 sessions (60 minutes), up to 2 per week, over a maximum of 3-months post baseline.

Both therapies are administered by an allied health professional (e.g., psychologist, social worker, psychiatrict nurse, occupational therapist) who has specific qualifications in administering cognitive behavioural therapy. Sessions will include formulating a personal social goal participants want to work on, and the Session Rating Scale (SRS). This is a simple, four-item visual analogue scale designed to assess key dimensions of effective therapeutic relationships.

Summary control condition VR-CBT 1.0:
The first session a personalised case formulation will be built with the participant, including social situations that provoke anxiety, dysfunctional thoughts, feelings, safety behaviours such as avoidance, escape and in-situ avoidance behaviour. It will also include a learning history including life events like bullying, neglect and traumatic experiences. A personal social goal will be formulated. Five minutes will be spent in a pleasant VR-environment to get familiar with the technique. Session 2-11 all follow the same structure. Ten minutes will be spent in talking about relevant events since the last session and in deciding what social environment will be used for exposure today. Then 40 minutes will be spent in a personalised exposure session, working towards the personal social goal (for example talking in front of the classroom) while using the information from the personal case formulation. After that 10 minutes will be used for reflection on the session. The 12th session VR can be used to do a final exposure, but will mostly be set up to establish what was learned from the sessions and how the participant will continue to use the gained knowledge and experience from the therapy.
Control group
Active

Outcomes
Primary outcome [1] 336564 0

Social Functioning: The primary outcome will be social functioning as measured by the Social and Occupational Functioning Assessment Scale (SOFAS) post intervention (6 months post treatment)
Timepoint [1] 336564 0
Baseline, Week 12 (post treatment), 6mths post treatment, 12mths post treatment
Secondary outcome [1] 428823 0
Social functioning in daily life: Social Functioning will also be measured by Ecological Momentary Assessment (EMA) to establish generalisation of virtual therapy effects to real life social situations.
Timepoint [1] 428823 0
Baseline, Week 12 (post treatment), 6mths post treatment, 12mths post treatment
Secondary outcome [2] 429324 0
Overall subjective social cognition will be measured using The Awareness of Social Inference Test – Short, an ecologically valid instrument that uses videos of actors engaged in everyday conversations to assess emotion perception, the ability to detect lies, sarcasm and sincerity, and the ability to judge what others are thinking, intending, feeling, and saying. Norm groups are available.
Timepoint [2] 429324 0
Baseline, Week 12 (post treatment), 6mths post treatment, 12mths post treatment
Secondary outcome [3] 431430 0
Cost-Effectiveness: Estimates of cost effectiveness will be generated by measures of quality of life (to calculate Quality-adjusted life years (QALYs)) and resource use (Resource Use Questionnaire).
Timepoint [3] 431430 0
post treatment (primary endpoint, 3 months post baseline), 6-months and 1-year follow-up.
Secondary outcome [4] 431431 0
Subjective social cognition will be measured by the self-report Observable Social Cognition Rating Scale (OSCARS), and is also used for screening purposes for the trial.
Timepoint [4] 431431 0
Baseline, Week 12 (post treatment), 6mths post treatment, 12mths post treatment
Secondary outcome [5] 431432 0
Safety behaviours (such as avoidance) will be assessed with The Safety Behaviour Questionnaire – persecutory delusions (SBQ) for social situations and has good psychometric properties.
Timepoint [5] 431432 0
Baseline, 3mths Post treatment, 6mths and 12mths post treatment
Secondary outcome [6] 431433 0
Emotion recognition: will be measured with The Penn Emotion Recognition Test (ER-40), a computer-based task that uses 40 colour photographs of posed facial expressions of four emotions (i.e., happiness, sadness, anger, or fear) as well as neutral.

Emotion recognition will also be measured by the Awareness of Social Inference Test –Short, an ecologically valid instrument that uses videos of actors engaged in everyday conversations to assess emotion perception, the ability to detect lies, sarcasm and sincerity, and the ability to judge what others are thinking, intending, feeling, and saying. Norm groups are available.
Timepoint [6] 431433 0
Baseline, 3mths, 6mths and 12mths post treatment
Secondary outcome [7] 431990 0
Theory of mind will be measured with the Hinting Task. This assesses the understanding of indirect speech requests through the presentation of 10 vignettes which depict everyday social interactions.
Timepoint [7] 431990 0
Baseline, 3mths, 6mths and 12mths post treatment
Secondary outcome [8] 431991 0
Social perception will be measured with The TASIT Part III Social Inference-Enriched, an ecologically valid, and clinically relevant instrument to assess the ability to detect deception (i.e., lies) and sarcasm in social encounters.
Timepoint [8] 431991 0
Baseline, 3mths, 6mths and 12mths post treatment
Secondary outcome [9] 431992 0
Attributional bias will be measured using the Ambiguous Intentions and Hostility Questionnaire (AIHQ), a reliable scale with items developed to reflect social situations that are ambiguous, intentional, and accidental in nature..
Timepoint [9] 431992 0
Baseline, 3mths, 6mths and 12mths post treatment

Eligibility
Key inclusion criteria
To be considered eligible, a young person must:
1. Meet threshold diagnostic criteria for first episode psychosis (FEP) (defined within DSM-5 all psychotic spectrum disorders or affective disorder with psychotic features who are within their first year of treatment for psychosis) or ultra-high risk for psychosis (UHR) (as assessed by the Comprehensive Assessment of At-Risk Mental State (CAARMS56). Note: this assessment will be conducted by clinicians at the referring clinic and will not form part of the research assessment schedule.
2. Be aged 14 – 30 years
3. Be receiving care from an early psychosis service at the time of recruitment in Melbourne, Adelaide or Perth
4. Have a Social and Occupational Functioning Assessment Scale (SOFAS) score <751

Service providers will be considered eligible for inclusion in this study if they:
1. Work at a participating study site, AND
2. Are responsible for delivering VR-CBT as part of the trial, OR
3, Are responsible for leading a team and or managing the service.
Minimum age
14 Years
Maximum age
30 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Young people will not be eligible for participation in this study if any of the below criteria are met:
1. They have cognitive impairment significant enough to impede participation in the study, as determined by treating clinician
2. They have insufficient command of the English language
3. They are currently an inpatient in an acute mental health ward
4. They have current active suicidal plans, with severe and imminent risk to their safety

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)
central randomisation by computer
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software (i.e. computerised sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
Statistical methods for this project are outlined separately below for Part one and two of the VISOR trial.
(1) Randomised Control Trial (RCT)
Intention to treat analyses will be used to evaluate differences in social functioning between the two treatment groups. Linear mixed-effects regression model will be carried out for repeated measures to evaluate differences in longitudinal trajectories between the two groups to test the hypotheses' that VR-CBT 2.0 is more effective for improving social functioning. This modelling technic both properly accounts for correlations induced by repeated measurements within subjects and produces unbiased estimates with missing observations (when missing at random). The intention-to-treat model will be estimated with (1) treatment group allocation, (2) time, treatment months, as the within-subjects factor, and (3) a group by time interaction to test for differential treatment effects.
(2) Comparison with TAU
Although the effectiveness of VR-CBT 1.0 has been previously demonstrated, we are seeking additional validation in this study by taking advantage of an existing project that collects clinical minimal data from headspace Early Psychosis (hEP) services nationally. Given randomisation will not be conducted we will apply a target trial emulation (Hernán, 2020), which is a state-of-art statistical modelling framework for causal evaluation using observational data. The target trial emulation involves: (1) identifying the control cohort with the same inclusion and exclusion criteria (except for service location); (2) mapping causal pathways between variables collected to identify confounding, mediating or modifying factors using DAGs; and (3) accounting for the impact of these factors using using G-computation and inverse probability-of-treatment weighting (IPTW) to isolate the treatment effect.
(3) Other Secondary Analysis
We will also conduct causal mediation analysis to evaluate whether VR-CBT 2.0 improves treatment responses via enhancing social cognition and reducing safety behaviours. Using the data collected, we will also explore longitudinal dynamic associations between treatment, social cognition, safety behaviours and social functioning using advance statistical modelling, with multilevel structural equation modelling. Factors associated with high treatment response will also be explored using machine learning prediction models. The MDS collected for clinical controls and treatment population will be used to explore a range of outcomes between TAU and the two VR treatment groups, such as general treatment engagement, clinical and functioning outcomes.

Economic evaluation will primarily comprise a cost utility analysis where the main outcome measure is (quality of adjusted life years (QALYs), however primary and secondary outcomes will also be compared to costs differences via a cost-consequence analysis. Two forms of analyses will be undertaken including a standard within trial economic evaluation as well as a population level modelled economic evaluation (including a budget impact analysis). The costs to be considered include the costs of delivering the VR-CBT intervention, other costs determined from the RUQ and linked data. Standardised techniques such as GLM analyses and bootstrapping for uncertainty will be undertaken. If, as expected, the intervention is found to be effective, lifetime and population cost-effectiveness of VRCBT 2.0 will be determined using modelling techniques refined and previously used by co-applicants.

(4) Implementation evaluation
Quantitative data from questionnaires completed by young people and service providers will be analysed using descriptive statistics. Questionnaires completed by service providers will be analysed using repeated measures analysis of variance to assess any changes in acceptability, feasibility and behavioural drivers over time. Qualitative interviews and focus groups will be recorded and transcribed for analysis. Data will be analysed using a Framework Analysis approach, routinely used in implementation research that includes: 1) familiarisation, 2) identifying a thematic framework, 3) indexing, 4) charting, and 5) mapping/interpretation; in the final phase, data can be summarised and organised to identify broad themes of interest and to answer research questions.
Data from the implementation evaluation will be triangulated with data from the main study to examine the relationship between user experiences, acceptability, and engagement with the intervention.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/08/2024
Actual
Date of last participant enrolment
Anticipated
30/04/2026
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
156
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA,WA,VIC

Funding & Sponsors
Funding source category [1] 314532 0
Charities/Societies/Foundations
Name [1] 314532 0
The Wellcome Trust Foundation
Country [1] 314532 0
United Kingdom
Primary sponsor type
Other
Name
Orygen
Address
35 Poplar Road Parkville, VIC 3052
Country
Australia
Secondary sponsor category [1] 317239 0
None
Name [1] 317239 0
Address [1] 317239 0
Country [1] 317239 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 313574 0
The Royal Melbourne Hospital Human Research Ethics Committee
Ethics committee address [1] 313574 0
Ethics committee country [1] 313574 0
Australia
Date submitted for ethics approval [1] 313574 0
29/11/2023
Approval date [1] 313574 0
23/04/2024
Ethics approval number [1] 313574 0
HREC/101261/MH-2023

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

Contacts
Principal investigator
Name 128602 0
Prof Andrew Thompson
Address 128602 0
Orygen, 35 Poplar Rd, Parkville VIC 3052
Country 128602 0
Australia
Phone 128602 0
+61457756565
Fax 128602 0
Email 128602 0
[email protected]
Contact person for public queries
Name 128603 0
Roos Pot-Kolder
Address 128603 0
Orygen, 35 Poplar Rd, Parkville VIC 3052
Country 128603 0
Australia
Phone 128603 0
+61467670731
Fax 128603 0
Email 128603 0
[email protected]
Contact person for scientific queries
Name 128604 0
Kate Reynolds
Address 128604 0
Orygen, 35 Poplar Rd, Parkville VIC 3052
Country 128604 0
Australia
Phone 128604 0
+61448152623
Fax 128604 0
Email 128604 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

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

Documents added automatically
No additional documents have been identified.