Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12624000357550
Ethics application status
Approved
Date submitted
26/02/2024
Date registered
28/03/2024
Date last updated
28/03/2024
Date data sharing statement initially provided
28/03/2024
Type of registration
Prospectively registered

Titles & IDs
Public title
Hybrid: Integrating Virtual Reality, Neurofeedback and Cognitive Behaviour Therapy for Treatment of Hearing Voices in Young People
Scientific title
Hybrid: Integrating Virtual Reality, Neurofeedback and Cognitive Behaviour Therapy for Treatment of Hearing Voices in Young People Experiencing Psychosis
Secondary ID [1] 311596 0
None
Universal Trial Number (UTN)
Trial acronym
Hybrid
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Early psychosis 333000 0
Schizophrenia 333001 0
Condition category
Condition code
Mental Health 329696 329696 0 0
Schizophrenia
Mental Health 329897 329897 0 0
Psychosis and personality disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Hybrid is a new, integrated approach for the treatment of auditory verbal hallucinations (AVH) in early psychosis that takes a ‘symptom capture’ approach using individually tailored virtual reality (VR)-based exposure exercises. Participants are progressively exposed to symptom triggers in a controlled VR environment and develop methods of down regulating neural activity associated with these symptoms (via neurofeedback) while concurrently receiving clinician-delivered CBT for psychosis (CBTp) in-vivo (i.e., during symptom activation). The study intervention consists of three elements delivered concurrently:

1. A VR exposure hierarchy to imitate real-world environments in which the participant has difficulty managing their AVH. Our approach is based within the CBTp framework and involves developing an understanding of the antecedents of hallucinatory experiences. The participant and therapist will then select a template scenario from pre-existing VR environments (e.g., supermarket, bedroom) where various aspects of the environment (such as the number of people, the proximity and gaze intensity of people, lighting, noise etc) can be personalised to create a hierarchy of symptom-provoking strategies. For each participant there will be five scaled variants of their personalised scenes which will be presented via a wearable VR headset.
2. Neurofeedback from electroencephalography (EEG) measurement. Specifically, neurofeedback of real-time EEG activity of high beta band activity will be presented to participants as a visual image of a thermometer in the corner of the VR headset. The participant will attempt to modulate neural activity associated with AVH. This will be visually represented by the thermometer reducing in temperature.
3. Cognitive-behaviour therapy with a clinician (member of research team) enhancing strategies for coping with symptoms.

The Hybrid intervention will take place over 14 weeks at Orygen Ltd in Parkville, Melbourne, Australia, and consists of two phases: the Preparation and Implementation Phases. The Hybrid Preparation phase will occur over a 2-week period following screening and baseline assessments. The Preparation phase will involve participants working with a clinically trained research team member to develop the tailored VR exposure hierarchies. The Hybrid Implementation Phase will consist of 12 sessions of 30-45 minutes each spread over 12 weeks. Participants will start on the lowest level of their exposure hierarchy and progressively work up the hierarchy over the course of the weekly sessions. The standard approach in exposure and response prevention interventions will be adopted, which is to reduce subjective units of distress to 30/100 before progressing to the next step in the hierarchy. While the participant is exposed to the symptom-eliciting VR scenario, they will engage in CBTp with their therapist (using open-back earphones) where the CBT will be standard, manualised CBT for voices, dealing with the active cognitions elicited by the VR scenario. Key elements include reassurance regarding lack of threat, challenging appraisals of AVH (e.g., their perceived power, threat, or dominance; reducing submissive or reactive behaviours), actively responding to AVH, and developing a sense of control over AVH by attempting to delay or reduce their volume or distract from them with a variety of strategies (e.g., humming, visualisation). Furthermore, participants will also be instructed to use the neurofeedback to reduce their level of distress within the VR environment. Each VR scenario will be used multiple times until the participant is comfortable and can progress to the next level in the hierarchy. The Hybrid pilot intervention will be delivered in addition to standard care received in (Early Psychosis Prevention & Intervention Centre (EPPIC).

We will monitor consent and completion rates; number of sessions attended; number of dropouts; completion rates of measures, and whether AVH were elicited in 80% or more of VR sessions. Furthermore, we will administer a semi-structured interview upon completion to gather information about participant’s experience of the intervention and suggestions for modifications to the treatment package.
Intervention code [1] 328050 0
Behaviour
Intervention code [2] 328051 0
Treatment: Devices
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 337486 0
Feasibility and acceptability (composite outcome)
Timepoint [1] 337486 0
14 weeks post intervention commencement (at the end of treatment)
Primary outcome [2] 337487 0
Safety
Timepoint [2] 337487 0
Continuously throughout each session of the trial and at 14 weeks post-intervention
Primary outcome [3] 337488 0
Usability
Timepoint [3] 337488 0
14 weeks post intervention commencement (at the end of treatment)
Secondary outcome [1] 432075 0
Auditory verbal hallucinations (composite outcome)
Timepoint [1] 432075 0
Baseline (start of the Preparation Phase) and 14 weeks post intervention commencement (at the end of treatment)
Secondary outcome [2] 432076 0
General psychopathology (composite outcome)
Timepoint [2] 432076 0
Baseline (start of the Preparation phase) and 14 weeks post intervention commencement (at the end of treatment)
Secondary outcome [3] 432077 0
Psychological treatment target
Timepoint [3] 432077 0
Continuously throughout each session of the trial and at 14 weeks post-intervention
Secondary outcome [4] 432078 0
Neuropsychological Treatment Target
Timepoint [4] 432078 0
Continuously throughout each session of the trial and at 14 weeks post-intervention

Eligibility
Key inclusion criteria
1) Aged 15-25 years inclusive.
2) Sufficient fluency in English to engage in psychological therapy with an English-speaking therapist, and to understand the study assessments.
3) Ability to give informed consent and adhere to study procedures. Parental or guardian consent will be obtained for participants aged under 18 years.
4) Psychotic threshold AVH as measured by the Comprehensive Assessment of At Risk Mental States (CAARMS; 5 or 6 on severity and greater than or equal to 4 on frequency for longer than one week; Yung et al., 2005)
5) A current rating of greater than or equal to 3 on the Psychotic Symptom Rating Scales (PSYRATS) hallucinations scale (Drake, Haddock, Tarrier, Bentall, & Lewis, 2007), corresponding to voices occurring at least once/hour. The purpose of this is to ensure that participants with reasonably frequent hallucinations are included in the study, as experience of symptoms during Hybrid sessions will optimise the study’s test of outcomes of interest.
Minimum age
15 Years
Maximum age
25 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion Criteria:
1) Documented history of head injury, seizures, or other significant neurological illness
2) Documented history of intellectual disability
3) Visual impairment precluding ability to view VR scenario

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Not Applicable
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
The primary outcome of this study will be reported descriptively as summary statistics and qualitatively for any user feedback. (1) Target scores: Means and standard deviations of acceptability, feasibility, safety measures and percentage of participants showing different levels of ratings on the Pilot Study Assessment Instrument will be reported. Qualitative data analysis will also be conducted by analysing participants’ responses to the Hybrid User Experience Survey including recommended modifications to the treatment package. The number of adverse events and serious adverse events will be reported. (2) Clinical efficacy: Effect sizes, paired t-tests and Wilcoxon analysis of clinical rating changes pre and post intervention will be computed, which will inform future efficacy trials. Whether greater engagement of neural and psychological targets is associated with greater change in clinical measures will also be explored. This finding would indicate a treatment mechanism that could be systematically tested in future studies.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
4/04/2024
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
10
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 26215 0
Orygen Youth Health - Parkville - Parkville
Recruitment hospital [2] 26216 0
Orygen Youth Health - Sunshine - Sunshine
Recruitment postcode(s) [1] 42181 0
3052 - Parkville
Recruitment postcode(s) [2] 42182 0
3020 - Sunshine

Funding & Sponsors
Funding source category [1] 315903 0
Government body
Name [1] 315903 0
National Health and Medical Research Council Investigator Grant (2026484)
Country [1] 315903 0
Australia
Primary sponsor type
Individual
Name
Barnaby Nelson
Address
Country
Australia
Secondary sponsor category [1] 318073 0
None
Name [1] 318073 0
Address [1] 318073 0
Country [1] 318073 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 314750 0
University of Melbourne Central Human Research Ethics Committee
Ethics committee address [1] 314750 0
Ethics committee country [1] 314750 0
Australia
Date submitted for ethics approval [1] 314750 0
04/07/2022
Approval date [1] 314750 0
28/07/2022
Ethics approval number [1] 314750 0

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

Contacts
Principal investigator
Name 132606 0
Prof Barnaby Nelson
Address 132606 0
Orygen Ltd. 35 Poplar Rd Parkville, VIC, 3052
Country 132606 0
Australia
Phone 132606 0
+61 3 9342 2800
Fax 132606 0
Email 132606 0
barnaby.nelson@orygen.org.au
Contact person for public queries
Name 132607 0
Elise Rowe
Address 132607 0
Orygen Ltd. 35 Poplar Rd Parkville, VIC, 3052
Country 132607 0
Australia
Phone 132607 0
+61 475 588 860
Fax 132607 0
Email 132607 0
elise.rowe@orygen.org.au
Contact person for scientific queries
Name 132608 0
Elise Rowe
Address 132608 0
Orygen Ltd. 35 Poplar Rd Parkville, VIC, 3052
Country 132608 0
Australia
Phone 132608 0
+61 475 588 860
Fax 132608 0
Email 132608 0
elise.rowe@orygen.org.au

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.