Schizophrenia Spectrum DisordersENGAGENCT06993831
ENGAGE: Virtual Reality-based Psychotherapy for Negative Symptoms in Schizophrenia
A study testing Virtual Reality-based psychotherapy in people with Schizophrenia Spectrum Disorders and Negative Symptoms in Schizophrenia, run by Mental Health Centre Copenhagen, Bispebjerg and Frederiksberg Hospital at 1 site in Denmark.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Schizophrenia Spectrum Disorders, Negative Symptoms in Schizophrenia
- What is being tested?
- Virtual Reality-based psychotherapy
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteDenmark
- Study dates
- 9 Dec 2024to 7 Jan 2026
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- ICD-10 diagnosis of a schizophrenia-spectrum disorder (F2x)
- Negative symptom score of ≥3 on the SANS items avolition or anhedonia
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
Denmark1 site
Copenhagen Research Center for Mental Health (CORE), Mental Health Services CPH, Denmark
Hellerup, Greater Copenhagen, 2900
About this study
Official title: ENGAGE Pilot Study: Alleviating Negative Symptoms in Schizophrenia Using a Virtual Reality-based Intervention Targeting Social Reward Learning
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:
Read more
- Is Virtual Reality-based therapy a feasible and acceptable treatment for negative symptoms in SSD?
- 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.
Read the 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.
- Being tested
- Virtual Reality-based psychotherapy
- Keywords
- schizophrenia, psychotherapy, VR, psychosocial intervention, psychosis, negative symptoms
- Medical subject headings
- Schizophrenia, Psychotic Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Virtual Reality-based psychotherapyBehavioural
Also called ENGAGE
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.
| Study group | Role | What they receive |
|---|---|---|
| Treatment as Usual | No intervention | Participants randomized to this arm will not receive any treatment beyond the standard care offered by the usual health care providers. |
| VR-based psychotherapy | Experimental | 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. Receives: Behavioral: Virtual Reality-based psychotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Feasibility and acceptability as assessed by recruitment rate
Percentage of target sample (30 participants) recruited after 15 months from study start
Measured: Recruitment rate is monitored throughout the study period (15 months)
Feasibility and acceptibility as assessed by retention rate
Percentage of included participants in the experimental group who retent to treatment at cessation of therapy (10 sessions)
Measured: Retention rates are monitored throughout the study period (15 months)
Feasibility and acceptability as assessed by level of satisfaction in the experimental group
Percentage of participants in the experimental group reporting a satisfaction rating of more than 7 on a 10-point Likert scale with higher scoring indicating a higher level of satisfaction with therapy.
Measured: At 12 weeks follow-up
Secondary outcomes (5)
Severity of negative symptoms as assessed by the Brief Negative Symptoms Scale (BNSS)
The BNSS is a an interviewer-administered instrument comprising 13 items and five domains of negative symptoms: anhedonia, asociality, avolition, blunted effect and alogia.
Each item is rated on a 7-point scale (0-6) with higher scores reflecting a higher level of negative symptoms.
Measured: Baseline and at 12 weeks follow-up
Severity of negative symptoms as assessed by the Scale for the Assessment of Negative Symptoms (SANS)
The SANS is an interviewer-administered instrument comprising 23 items and four domains of negative symptoms: affective flattening or blunting, alogia, avolition-apathy, and anhedonia-asociality.
Each item is rated on a 5-point scale (0-5) with higher scores reflecting a higher level of negative symptoms.
Measured: Baseline and at 12 weeks follow-up
Severity of negative symptoms as assessed by the Self-evaluation of Negative Symptoms (SNS)
The SNS is a patient questionnaire comprising 20 items and 5 domains of negative symptoms: social withdrawal, diminished emotional range, alogia, avolition, and anhedonia.
Each item is rated on a 3-point scale (0-2) with higher scores reflecting higher levels of negative symptoms.
Measured: Baseline and at 12 weeks follow-up
Social and daily functioning as assessed by the Personal and Social Performance Scale (PSP)
The PSP is an interviewer-administered instrument assessing different domains of social and daily functioning: socially useful activities, personal and social relationships, self-care, and disturbing and aggressive behavior.
A score between 1-100 is assigned with higher scores indicating better functioning.
Measured: Baseline and at 12 weeks follow-up
Social functioning as assessed by the Social Functioning Scale (SFS)
The SFS is a self-report instrument assessing social functioning among individuals with schizophrenia.
The instrument comprises seven domains: Social engagement/withdrawal, Interpersonal behaviour, Prosocial activities, Recreation, Independence-competence, Independence-performance and Employment/occupation.
The minimum raw score is 0 and maximum raw score is 223 with higher scoring indicating a higher level of functioning.
Measured: Baseline and at 12 weeks follow-up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 May 2025
- Study start9 Dec 2024
- Primary completion7 Jan 2026
- Study completion7 Jan 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Schizophrenia Spectrum DisordersStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mental Health Centre Copenhagen, Bispebjerg and Frederiksberg Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Glostrup University Hospital, Copenhagen
- Responsible party
- Sponsor
- Investigators
- Louise B Glenthøj, PhD, dr.med., Principal investigator, VIRTU Research Group, Mental Health Center Copenhagen, Copenhagen University Hospital - Mental Health Services CPH, Denmark
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06993831
- Sponsor's protocol ID
- H-24046055
- Other IDs
- H-24046055
- Acronym
- ENGAGE
- Status last verified
- Jan 2026
- First submitted
- 21 Feb 2025
- Last updated
- 9 Jan 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 41060907
Study at a glance
From the registry record, last updated by the sponsor on 9 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- ENGAGE Pilot Study: Alleviating Negative Symptoms in Schizophrenia Using a Virtual Reality-based Intervention Targeting Social Reward Learning
- ClinicalTrials.gov ID
- NCT06993831
- Acronym / sponsor ID
- ENGAGE / H-24046055
- Keywords
- schizophrenia, psychotherapy, VR, psychosocial intervention, psychosis, negative symptoms
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Mental Health Centre Copenhagen, Bispebjerg and Frederiksberg HospitalUniversity, hospital or other
- Collaborators
- Glostrup University Hospital, Copenhagen
- Study start
- 9 Dec 2024 (actual)
- Primary completion
- 7 Jan 2026 (actual)
- Study completion
- 7 Jan 2026 (actual)
- First posted
- 29 May 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- Is Virtual Reality-based therapy a feasible and acceptable treatment for negative symptoms in SSD?
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Treatment as Usual | No intervention | –Participants randomized to this arm will not receive any treatment beyond the standard care offered by the usual health care providers. |
| VR-based psychotherapy | Experimental | Behavioral: Virtual Reality-based psychotherapyParticipants 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. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- ICD-10 diagnosis of a schizophrenia-spectrum disorder (F2x)
- Negative symptom score of ≥3 on the SANS items avolition or anhedonia
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Virtual Reality-based psychotherapyAlso: ENGAGEA 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. | Behavioural | VR-based psychotherapy |
Primary outcome
Feasibility and acceptability as assessed by recruitment rate
Time frame: Recruitment rate is monitored throughout the study period (15 months)
Percentage of target sample (30 participants) recruited after 15 months from study start
Feasibility and acceptibility as assessed by retention rate
Time frame: Retention rates are monitored throughout the study period (15 months)
Percentage of included participants in the experimental group who retent to treatment at cessation of therapy (10 sessions)
Feasibility and acceptability as assessed by level of satisfaction in the experimental group
Time frame: At 12 weeks follow-up
Percentage of participants in the experimental group reporting a satisfaction rating of more than 7 on a 10-point Likert scale with higher scoring indicating a higher level of satisfaction with therapy.
5 secondary outcomes
Severity of negative symptoms as assessed by the Brief Negative Symptoms Scale (BNSS)
Time frame: Baseline and at 12 weeks follow-up
Severity of negative symptoms as assessed by the Scale for the Assessment of Negative Symptoms (SANS)
Time frame: Baseline and at 12 weeks follow-up
Severity of negative symptoms as assessed by the Self-evaluation of Negative Symptoms (SNS)
Time frame: Baseline and at 12 weeks follow-up
Social and daily functioning as assessed by the Personal and Social Performance Scale (PSP)
Time frame: Baseline and at 12 weeks follow-up
Social functioning as assessed by the Social Functioning Scale (SFS)
Time frame: Baseline and at 12 weeks follow-up
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jan 2026.
- Derived from this study: PubMed 41060907Donath 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Louise B Glenthøj, PhD, dr.med. principal investigator
VIRTU Research Group, Mental Health Center Copenhagen, Copenhagen University Hospital - Mental Health Services CPH, Denmark
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Virtual Reality-based psychotherapy in people with Schizophrenia Spectrum Disorders and Negative Symptoms in Schizophrenia, run by Mental Health Centre Copenhagen, Bispebjerg and Frederiksberg Hospital at 1 site in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Feasibility and acceptability as assessed by recruitment rate (time frame: Recruitment rate is monitored throughout the study period (15 months)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06993831, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Jan 2026.