Clinical trial NCT06993831: ENGAGE: Virtual Reality-based Psychotherapy for Negative Symptoms in Schizophrenia
Official title: ENGAGE Pilot Study: Alleviating Negative Symptoms in Schizophrenia Using a Virtual Reality-based Intervention Targeting Social Reward Learning
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Schizophrenia Spectrum Disorders
Negative Symptoms in Schizophrenia
Keywords: schizophrenia
psychotherapy
VR
psychosocial intervention
psychosis
negative symptoms
Lead sponsor: Mental Health Services in the Capital Region, Denmark
Sponsor class: OTHER
Collaborators: name: CNSR, Glostrup Psychiatric Center
First posted: 2025-05-29
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary goal of this pilot study is to examine the feasibility and acceptability of a new Virtual Reality-based intervention against negative symptoms in schizophrenia spectrum disorders (SSD).

The main questions it aims to answer are:

1. Is Virtual Reality-based therapy a feasible and acceptable treatment for negative symptoms in SSD?
2. Are there indications that the treatment is effective in reducing negative symptoms, improving daily functioning, and enhancing quality of life?

Researchers will compare the new Virtual Reality-based treatment to standard psychiatric care to evaluate therapy effectiveness.

Participants will be allocated to receive either 10 sessions of Virtual Reality-based therapy or Treatment as usual. All participants will undergo a thorough assessment at baseline and at follow-up after 12 weeks.

Detailed description: Negative symptoms (NS) are core features of schizophrenia and strongly correlated with vocational and social outcomes, quality of life, and have a higher impact on later outcome than positive symptoms (PS) such as hallucinations and delusions. While there are good medical treatment options for PS, no robust and replicated evidence exists for effective NS treatments. Consistent evidence suggests that abnormalities of the brain reward system are central in the pathogenesis of NS, i.e., the domains of anhedonia and avolition. Preliminary evidence indicates changes in reward learning following therapy is related to a reduction in NS.

Virtual reality (VR) is a promising technologically advanced mental health research tool with high ecological validity. VR allows individuals to immerse themselves in realistic environments and interact with virtual objects, providing a safe and controlled space to address symptoms and improve functioning. Initial evidence (N=4) supports that VR-based interventions significantly reduce NS and improve psychosocial functioning with a medium to large effect size. Given the suggested central role of reward processing disturbances in the pathogenesis of NS, there is an obvious need to investigate the effect of a VR-based intervention targeting reward processing in ameliorating NS.

Both NS and motivational abnormalities reflect complex processes at a system level likely corresponding to functional brain activity within and between several regions and circuits. Supplementing the clinical assessments in the study with magnetic resonance imaging (MRI) data may clarify whether the intervention directly targeting reward processing has an effect on the biological processes/networks involved.

In sum, this study will explore the prospects of using an innovative, VR-based treatment to treat NS and reward processing deficits in schizophrenia aimed at producing real-life benefits for the patients. If found successful, this pilot study could lay the foundation for a larger randomized clinical trial examining the intervention's effectiveness. Prospectively, these results can pave the way for a much sought-after treatment option for NS.

Eligibility criteria: Inclusion Criteria:

* ICD-10 diagnosis of a schizophrenia-spectrum disorder (F2x)
* Negative symptom score of ≥3 on the SANS items avolition or anhedonia

Exclusion Criteria:

* Diagnosis of organic brain disease
* Intellectual disability (IQ \< 70)
* Current diagnosis of drug dependency
* Command of spoken Danish or English inadequate for engaging in therapy
* Refusing to be informed on incidental findings on the MRI scans

Primary outcomes:
measure: Feasibility and acceptability as assessed by recruitment rate
timeFrame: Recruitment rate is monitored throughout the study period (15 months)
measure: Feasibility and acceptibility as assessed by retention rate
timeFrame: Retention rates are monitored throughout the study period (15 months)
measure: Feasibility and acceptability as assessed by level of satisfaction in the experimental group
timeFrame: At 12 weeks follow-up
Secondary outcomes:
measure: Severity of negative symptoms as assessed by the Brief Negative Symptoms Scale (BNSS)
timeFrame: Baseline and at 12 weeks follow-up
measure: Severity of negative symptoms as assessed by the Scale for the Assessment of Negative Symptoms (SANS)
timeFrame: Baseline and at 12 weeks follow-up
measure: Severity of negative symptoms as assessed by the Self-evaluation of Negative Symptoms (SNS)
timeFrame: Baseline and at 12 weeks follow-up
measure: Social and daily functioning as assessed by the Personal and Social Performance Scale (PSP)
timeFrame: Baseline and at 12 weeks follow-up
measure: Social functioning as assessed by the Social Functioning Scale (SFS)
timeFrame: Baseline and at 12 weeks follow-up
Other outcomes:
measure: Psychological well-being as assessed by The World Health Organisation- Five Well-Being Index (WHO-5)
timeFrame: Baseline and at 12 weeks follow-up
measure: Level of depressive symptoms as assessed by the Calgary Depression Scale for Schizophrenia (CDSS)
timeFrame: Baseline and at 12 weeks follow-up
measure: Perceived interpersonal pleasure as assessed by the Anticipatory and Consummatory Interpersonal Pleasure Scale (ACIPS)
timeFrame: Baseline and at 12 weeks follow-up
measure: Defeatist performance beliefs as assessed by the Defeatist Performance Attitude Scale (DPAS)
timeFrame: Baseline and at 12 weeks follow-up
measure: Severity of positive symptoms as assessed by the Scale for the Assessment of Positive Symptoms (SAPS)
timeFrame: Baseline and at 12 weeks follow-up
measure: Emotion processing capability as assessed by the Emotion Recognition Task (CANTAB ERT)
timeFrame: Baseline and at 12 weeks follow-up
measure: Readiness for therapy as assessed by the Readiness for Therapy Questionnaire (RTQ)
timeFrame: Baseline and at 12 weeks follow-up
measure: Client satisfaction as assessed by the Client Satisfaction Questionnaire (CSQ)
timeFrame: Baseline and at 12 weeks follow-up
measure: Virtual Reality simulation sickness as assessed by the Virtual Reality Simulation Sickness Questionnaire, Modified Danish Version (VRSSQ-MDV)
timeFrame: Baseline and at 12 weeks follow-up
measure: Immersion in VR as assessed by the Multimodal Presence Scale, Modified Shortened Danish Version (MPS-MSDV)
timeFrame: Baseline and at 12 weeks follow-up
measure: Reward system activation in mesocorticolimbic and fronto-striatal circuits as assessed by functional magnetic resonance imaging (MRI)
timeFrame: Baseline and at 12 weeks follow-up
measure: Positive affect (Ecological Momentary Assessment)
timeFrame: Baseline and at 12 weeks follow-up
measure: Negative affect (Ecological Momentary Assessment)
timeFrame: Baseline and at 12 weeks follow-up
measure: Consummatory and anticipatory hedonia (Ecological Momentary Assessment)
timeFrame: Baseline and at 12 weeks follow-up
measure: Number of self-reported activities (Ecological Momentary Assessment)
timeFrame: Baseline and at 12 weeks follow-up
measure: Number of self-reported companions (Ecological Momentary Assessment)
timeFrame: Baseline and at 12 weeks follow-up
measure: Asociality (Ecological Momentary Assessment)
timeFrame: Baseline and at 12 weeks follow-up
measure: Avolition (Ecological Momentary Assessment)
timeFrame: Baseline and at 12 weeks follow-up
measure: Sedentary behavior (Ecological Momentary Assessment)
timeFrame: Baseline and at 12 weeks follow-up
measure: Time spent at home (Ecological Momentary Assessment)
timeFrame: Baseline and at 12 weeks follow-up
Locations:
city: Hellerup
country: Denmark
facility: Copenhagen Research Center for Mental Health (CORE), Mental Health Services CPH, Denmark
state: Greater Copenhagen
Study officials:
affiliation: VIRTU Research Group, Mental Health Center Copenhagen, Copenhagen University Hospital - Mental Health Services CPH, Denmark
name: Louise B Glenthøj, PhD, dr.med.
role: PRINCIPAL_INVESTIGATOR
References: