ENGAGE: Virtual Reality-based Psychotherapy for Negative Symptoms in Schizophrenia

NCT ID: NCT06993831

Last Updated: 2026-01-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-12-09
• Study Completion Date: 2026-01-07

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.

Conditions

Schizophrenia Spectrum Disorders; Negative Symptoms in Schizophrenia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Treatment as Usual

Participants randomized to this arm will not receive any treatment beyond the standard care offered by the usual health care providers.

Group Type: NO_INTERVENTION

No interventions assigned to this group

VR-based psychotherapy

Participants randomized to this arm will receive 10 sessions of the VR-based intervention targeting negative symptoms in schizophrenia in addition to any possible treatment offered by other health care providers.

Group Type: EXPERIMENTAL

Virtual Reality-based psychotherapy

Intervention Type: BEHAVIORAL

A manualized, modularized, Virtual Reality-based intervention comprising 10 sessions of 1 hour each. The VR therapy aims at enhancing anticipatory pleasure and positive emotions by amplifying exposure and reactivity towards social environments and rewarding activities using a highly elaborate VR software. The VR exposure comprises several different virtual social environments (e.g., a bus, a café, a park etc.) In a tailored treatment approach, therapists will guide participants to train focusing on positive stimuli, engage in activities, experience social rewards, and practice expressing emotions through body language.

The therapy focuses on increasing the awareness of positive outcomes that may influence motivation. The therapy deploys activity appraisal/re-appraisal intended to enhance the salience of future opportunities for reward and desire for such rewards, thus targeting reward anticipation processes and promoting enjoyable daily-life activities.

Interventions

Virtual Reality-based psychotherapy

A manualized, modularized, Virtual Reality-based intervention comprising 10 sessions of 1 hour each. The VR therapy aims at enhancing anticipatory pleasure and positive emotions by amplifying exposure and reactivity towards social environments and rewarding activities using a highly elaborate VR software. The VR exposure comprises several different virtual social environments (e.g., a bus, a café, a park etc.) In a tailored treatment approach, therapists will guide participants to train focusing on positive stimuli, engage in activities, experience social rewards, and practice expressing emotions through body language.

The therapy focuses on increasing the awareness of positive outcomes that may influence motivation. The therapy deploys activity appraisal/re-appraisal intended to enhance the salience of future opportunities for reward and desire for such rewards, thus targeting reward anticipation processes and promoting enjoyable daily-life activities.

Intervention Type: BEHAVIORAL

Other Intervention Names

ENGAGE

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

CNSR, Glostrup Psychiatric Center

UNKNOWN

Sponsor Role: collaborator

Mental Health Services in the Capital Region, Denmark

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Louise B Glenthøj, PhD, dr.med.

Role: PRINCIPAL_INVESTIGATOR

VIRTU Research Group, Mental Health Center Copenhagen, Copenhagen University Hospital - Mental Health Services CPH, Denmark

Locations

Copenhagen Research Center for Mental Health (CORE), Mental Health Services CPH, Denmark

Hellerup, Greater Copenhagen, Denmark

Countries

Denmark

References

Donath VM, Ries ES, Mariegaard L, Kristensen TD, Ebdrup BH, Strauss GP, Fisher PM, Rostrup E, Nordentoft M, Hilker R, Melau M, Bockting CL, Albert N, van Bennekom MJ, Ambrosen KS, Glenthoj LB. Alleviating negative symptoms in schizophrenia using a virtual reality-based therapy targeting social reward learning (ENGAGE): Protocol for a randomised, controlled, assessor-blind pilot study. PLoS One. 2025 Oct 8;20(10):e0331632. doi: 10.1371/journal.pone.0331632. eCollection 2025.

Reference Type: DERIVED

PMID: 41060907 (View on PubMed)

Other Identifiers

H-24046055

Identifier Type: OTHER

Identifier Source: secondary_id

H-24046055

Identifier Type: -

Identifier Source: org_study_id