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| ID | Type | Description | Link |
|---|---|---|---|
| H-24046055 | Other Identifier | De Videnskabsetiske Komiteer for Region Hovedstaden |
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| Name | Class |
|---|---|
| Glostrup University Hospital, Copenhagen | OTHER |
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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:
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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Virtual Reality-based psychotherapy | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Feasibility and acceptability as assessed by recruitment rate | Percentage of target sample (30 participants) recruited after 15 months from study start | 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) | 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. | At 12 weeks follow-up |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Baseline and at 12 weeks follow-up |
| Measure | Description | Time Frame |
|---|---|---|
| Psychological well-being as assessed by The World Health Organisation- Five Well-Being Index (WHO-5) | The WHO-5 is a self-report questionnaire with 5 items measuring subjective psychological well-being. Each item is scored on a 6-point scale ranging At no time (0) to All of the time (5). A total raw score is ranging from 0 to 25. To calculate the final score, the total raw score is multiplied by 4 with higher scores reflecting higher levels of well-being. |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Louise B Glenthøj, PhD, dr.med. | VIRTU Research Group, Mental Health Center Copenhagen, Copenhagen University Hospital - Mental Health Services CPH, Denmark | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Copenhagen Research Center for Mental Health (CORE), Mental Health Services CPH, Denmark | Hellerup | Greater Copenhagen | 2900 | Denmark |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 41060907 | Derived | 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. |
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| ID | Term |
|---|---|
| D012559 | Schizophrenia |
| D011618 | Psychotic Disorders |
| ID | Term |
|---|---|
| D019967 | Schizophrenia Spectrum and Other Psychotic Disorders |
| D001523 | Mental Disorders |
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| ID | Term |
|---|---|
| C470748 | engage 8200 |
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| 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. | 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. | 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. | 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. | Baseline and at 12 weeks follow-up |
| Baseline and at 12 weeks follow-up |
| Level of depressive symptoms as assessed by the Calgary Depression Scale for Schizophrenia (CDSS) | The CDSS is an interviewer-administered instrument comprising 9 items assessing level of depression among individuals with schizophrenia. Each item is rated on a 4-point scale ranging from Absent (0) to Severe (3) with higher scores indicating a higher level of depressive symptoms. | Baseline and at 12 weeks follow-up |
| Perceived interpersonal pleasure as assessed by the Anticipatory and Consummatory Interpersonal Pleasure Scale (ACIPS) | The ACIPS is a patient questionnaire comprising 17 items assessing hedonic capacity for social interaction and interpersonal engagement. Each item is rated on a 6-point scale (1-6) with higher scores reflecting higher levels of hedonic capacity. | Baseline and at 12 weeks follow-up |
| Defeatist performance beliefs as assessed by the Defeatist Performance Attitude Scale (DPAS) | The DPAS is a self-report instrument comprising 15 items assessing defeatist performance beliefs. Each item is rated on a 7-point scale (1-7) with higher scores reflecting stronger defeatist performance beliefs (range: 15-105). | Baseline and at 12 weeks follow-up |
| Severity of positive symptoms as assessed by the Scale for the Assessment of Positive Symptoms (SAPS) | SAPS is an interviewer-administered instrument with 34 items measuring severity of hallucinations, delusions, bizarre behavior and positive formal thought disorder. Each item is rated on a 6-point scale (0-5) with higher scores reflecting higher levels of positive symptoms. | Baseline and at 12 weeks follow-up |
| Emotion processing capability as assessed by the Emotion Recognition Task (CANTAB ERT) | Computer-morphed images derived from the facial features of real individuals, each showing a specific emotion, are displayed on the screen, one at a time. Each face is displayed for 200ms and then immediately covered up to prevent residual processing of the image. The participant must select which emotion the face displayed from 6 options (sadness, happiness, fear, anger, disgust or surprise).The outcome measures for ERT cover percentage and number correct or incorrect and overall response latencies, which can be looked at either across individual emotions or across all emotions at once. | Baseline and at 12 weeks follow-up |
| Readiness for therapy as assessed by the Readiness for Therapy Questionnaire (RTQ) | RTQ is a 6-item self-report questionnaire measuring the participants positive attitude and preparedness to enter therapy for the purpose of resolving problems. Each item is scored on a 5-point Likert scale ranging from strongly disagree (0) to strongly agree (4). Item 2, 3 and 6 are reversed scored. A higher score indicates greater readiness for therapy. | Baseline and at 12 weeks follow-up |
| Client satisfaction as assessed by the Client Satisfaction Questionnaire (CSQ) | CSQ is an 8 item self-report measuring client satisfaction with the intervention. All items are scored on a 4-point Likert scale ranging from bad (1) to excellent (4). Higher scores indicate higher satisfaction. | Baseline and at 12 weeks follow-up |
| Virtual Reality simulation sickness as assessed by the Virtual Reality Simulation Sickness Questionnaire, Modified Danish Version (VRSSQ-MDV) | VRSSQ-MDV is a is a self-report questionnaire measuring virtual reality simulation sickness. The Modified Danish Version consists of 9 items rated on a 4-point Likert Scale ranging from 0 (not at all) to 3 (a lot). Higher scores reflect higher degree of virtual reality simulation sickness. The VRSSQ-MDV will be administered only to participants in the experimental group. | Baseline and at 12 weeks follow-up |
| Immersion in VR as assessed by the Multimodal Presence Scale, Modified Shortened Danish Version (MPS-MSDV) | MPS-MSDV is a self-report questionnaire measuring presence in virtual reality. The modified, shortened Danish Version consists of 10 selected items scored on a 5-point Likert Scale ranging from 1 (Strongly disagree) to 5 (Strongly agree). Higher scores reflect higher degree of presence in Virtual Reality. The MPS-MSDV will be administered only to participants in the experimental group. | Baseline and at 12 weeks follow-up |
| Reward system activation in mesocorticolimbic and fronto-striatal circuits as assessed by functional magnetic resonance imaging (MRI) | Brain activation during anticipation of monetary and social rewards will be examined using two functional paradigms, the Social Incentive Delay Task (SIDT) and the Monetary Incentive Delay Task (MIDT). Key regions of interest for the study include mesocorticolimbic and fronto-striatal circuits including ventral tegmental area, amygdala, hippocampus, striatum, nucleus accumbens, and prefrontal cortex. Additionally, resting state fMRI will be acquired. | Baseline and at 12 weeks follow-up |
| Positive affect (Ecological Momentary Assessment) | Ecological Momentary Assessment (EMA) will be employed capturing momentary features of negative symptoms at 5 randomly distributed timepoints per day over a 7-day course. Using a purpose-designed questionnaire, positive affect will be measured on a 4-item visual analogue scale from 0 to 10 with higher values indicating greater positive affect. | Baseline and at 12 weeks follow-up |
| Negative affect (Ecological Momentary Assessment) | Ecological Momentary Assessment (EMA) will be employed capturing momentary features of negative symptoms at 5 randomly distributed timepoints per day over a 7-day course. Using a purpose-designed questionnaire, negative affect will be measured on a 4-item visual analogue scale from 0 to 10 with higher values indicating greater negative affect. | Baseline and at 12 weeks follow-up |
| Consummatory and anticipatory hedonia (Ecological Momentary Assessment) | Ecological Momentary Assessment (EMA) will be employed capturing momentary features of negative symptoms at 5 randomly distributed timepoints per day over a 7-day course. Using a purpose-designed questionnaire, consummatory and anticipatory hedonia in reaction to activities will be measured on a 2-item visual analogue scale from 0 to 10 with higher values indicating greater negative affect. | Baseline and at 12 weeks follow-up |
| Number of self-reported activities (Ecological Momentary Assessment) | Ecological Momentary Assessment (EMA) will be employed capturing momentary features of negative symptoms at 5 randomly distributed timepoints (beeps) per day over a 7-day course. Using a purpose-designed questionnaire, the number of self-reported activities at each beep and the number of beeps without any activities will be recorded. | Baseline and at 12 weeks follow-up |
| Number of self-reported companions (Ecological Momentary Assessment) | Ecological Momentary Assessment (EMA) will be employed capturing momentary features of negative symptoms at 5 randomly distributed timepoints (beeps) per day over a 7-day course. Using a purpose-designed questionnaire, the number of self-reported companions and the number of beeps in absence of company will be recorded. | Baseline and at 12 weeks follow-up |
| Asociality (Ecological Momentary Assessment) | Ecological Momentary Assessment (EMA) will be employed capturing momentary features of negative symptoms at 5 randomly distributed timepoints per day over a 7-day course. Using a purpose-designed questionnaire, asociality in reaction to being alone or in company will be measured on a 4-item visual analogue scale from 0 to 10 (of which two items are inversely coded) with higher values indicating greater asociality. | Baseline and at 12 weeks follow-up |
| Avolition (Ecological Momentary Assessment) | Ecological Momentary Assessment (EMA) will be employed capturing momentary features of negative symptoms at 5 randomly distributed timepoints per day over a 7-day course. Using a purpose-designed questionnaire, avolition will be measured on a 2-item visual analogue scale from 0 to 10 with lower values indicating greater levels of avolition. | Baseline and at 12 weeks follow-up |
| Sedentary behavior (Ecological Momentary Assessment) | Ecological Momentary Assessment (EMA) will be employed capturing momentary features of negative symptoms at 5 randomly distributed timepoints per day over a 7-day course. Time spent on sedentary behaviors will be calculated from accelerometry data recorded from participants' mobile phone sensors. | Baseline and at 12 weeks follow-up |
| Time spent at home (Ecological Momentary Assessment) | Ecological Momentary Assessment (EMA) will be employed capturing momentary features of negative symptoms at 5 randomly distributed timepoints per day over a 7-day course. As an objectively measurable feature of inactivity, time spent at home will be calculated from location data recorded from participants' mobile phone sensors. | Baseline and at 12 weeks follow-up |