Virtual Reality-Based Cognitive Remediation in Schizophrenia and Bipolar Disorder

FULL-MINDSET- Fully Immersive Virtual Reality-based Cognitive Training in Schizophrenia and Bipolar Disorder: a Single Blind Randomized Controlled Trial in a Real-world Setting

This randomized controlled trial aims to evaluate the effectiveness of a virtual reality-based cognitive remediation (VRCR) intervention in improving cognitive performance and psychosocial functioning in individuals with schizophrenia spectrum disorders (SSD) and bipolar disorder (BD).

A total of 80 participants (40 with SSD and 40 with BD) will be randomly assigned in a 1:1 ratio to receive either VRCR or treatment as usual (TAU). The VRCR intervention will be delivered using the CEREBRUM platform and will consist of 45-minute sessions administered twice weekly for 12 weeks under the supervision of trained therapists.

The primary outcomes are changes in cognitive performance and psychosocial functioning, assessed using the MATRICS Consensus Cognitive Battery (MCCB) and the Personal and Social Performance (PSP) scale, respectively. Secondary outcomes include clinical symptom severity, assessed with validated rating scales, and neurobiological correlates, including functional magnetic resonance imaging (fMRI) and genetic biomarkers.

Assessments will be conducted at baseline, at 3 months (post-intervention), and at 6 months (follow-up). fMRI assessments will be conducted at baseline in patients with schizophrenia spectrum disorders, whereas peripheral blood samples for genetic marker analyses will be collected at baseline and at the 3-month follow-up in patients with SSD and BD. This study is expected to provide evidence on the feasibility, acceptability, and effectiveness of VR-based cognitive remediation in SSD and BD, as well as insights into the neurobiological mechanisms underlying cognitive and functional improvements.

Study Overview

• Status: Active, not recruiting
• Conditions: Bipolar Disorder (BD); Schizophrenia Spectrum Disorders (SSD)
• Intervention / Treatment: Behavioral: Virtual Reality Cognitive Remediation (VRCR); Other: Treatment as Usual (TAU)

• Study Type: Interventional
• Enrollment (Actual): 80
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Italy
  • Lombardy
    • Brescia, Lombardy, Italy, 25123
      • ASST Spedali Civili di Brescia - Department of Mental Health and Addiction Services

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥ 18 years
• Diagnosis of schizophrenia spectrum disorder or bipolar disorder (DSM-5)
• Clinical stability for at least 3 months
• Ability to provide informed consent

Exclusion Criteria:

• neurological disorders
• intellectual disability
• inability to participate in VR-based interventions due to medical or sensory limitations.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Participants with diagnosis of schizophrenia receiving VRCR	Behavioral: Virtual Reality Cognitive Remediation (VRCR); Participants in the VRCR group will receive individualized cognitive training using the CEREBRUM platform (IDEGO, Rome, Italy). CEREBRUM is an immersive virtual reality software where the user wearing the viewer sees a virtual environment that can be explored at 360°; it consists of 52 ecologically valid exercises of varying difficulty: 22 belonging to the Memory, and Learning Module, 10 to the Cognitive Estimates Module and 20 to the Attention and Working Memory Module. The difficulty of exercises is adaptable to provide adequately implement scaffolding and errorless learning principles, and the exercises require active interaction with the therapist. The software is compatible with the Oculus Go virtual reality viewer, a device with CE obligation. The program consists of 12 weeks of individual training, delivered twice weekly in 45-minute sessions in a controlled setting, from T0 (baseline) to T1 (3 months after T0).
Active Comparator: Participants with diagnosis of schizophrenia receiving standard clinical care; Participants receiving standard clinical care, including pharmacological treatment and case management	Other: Treatment as Usual (TAU); Standard clinical care including pharmacological treatment and case management according to routine clinical practice.
Experimental: Participants with diagnosis of bipolar disorder receiving VRCR	Behavioral: Virtual Reality Cognitive Remediation (VRCR); Participants in the VRCR group will receive individualized cognitive training using the CEREBRUM platform (IDEGO, Rome, Italy). CEREBRUM is an immersive virtual reality software where the user wearing the viewer sees a virtual environment that can be explored at 360°; it consists of 52 ecologically valid exercises of varying difficulty: 22 belonging to the Memory, and Learning Module, 10 to the Cognitive Estimates Module and 20 to the Attention and Working Memory Module. The difficulty of exercises is adaptable to provide adequately implement scaffolding and errorless learning principles, and the exercises require active interaction with the therapist. The software is compatible with the Oculus Go virtual reality viewer, a device with CE obligation. The program consists of 12 weeks of individual training, delivered twice weekly in 45-minute sessions in a controlled setting, from T0 (baseline) to T1 (3 months after T0).
Active Comparator: Participants with diagnosis of bipolar disorder receiving standard clinical care; Participants receiving standard clinical care, including pharmacological treatment and case management	Other: Treatment as Usual (TAU); Standard clinical care including pharmacological treatment and case management according to routine clinical practice.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in cognitive performance measured by MATRICS Consensus Cognitive Battery (MCCB) total score	Cognitive performance will be assessed using the MATRICS Consensus Cognitive Battery (MCCB), a standardized neuropsychological battery evaluating processing speed, attention/vigilance, working memory, verbal learning, visual learning, reasoning/problem solving, and social cognition.	Baseline, 3 months (end of the intervention), and 6 months
Change in psychosocial functioning measured by Personal and Social Performance (PSP) scale	Psychosocial functioning will be assessed using the Personal and Social Performance (PSP) scale, which evaluates socially useful activities, personal and social relationships, self-care, and disturbing or aggressive behaviors.	Baseline, 3 months (end of the intervention), and 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Clinical Global Impression (CGI) severity score		Baseline, 3 months (end of the intervention), and 6 months
Change in Positive and Negative Syndrome Scale (PANSS) total score in participants with schizophrenia spectrum disorders		Baseline, 3 months (end of the intervention), and 6 months
Change in Brief Negative Symptom Scale (BNSS) total score in participants with schizophrenia spectrum disorders		Baseline, 3 months (end of the intervention), and 6 months
Change in Hamilton Depression Rating Scale (HAM-D) total score in participants with bipolar disorder		Baseline, 3 months (end of the intervention), and 6 months
Change in Young Mania Rating Scale (YMRS) total score in participants with bipolar disorder		Baseline, 3 months (end of the intervention), and 6 months
Neurobiological correlates assessed by functional magnetic resonance imaging (fMRI) in patients with a diagnosis of SSD		Baseline
Changes in neuroplasticity-related biomarkers (BDNF, VEGF, DYRK1A)	Blood samples will be analyzed to assess biomarkers associated with neuroplasticity and cognitive functioning in patients with SSD and BD.	Baseline to 3 months (end of the intervention)

Collaborators and Investigators

• Sponsor: Università degli Studi di Brescia
• Investigators: Study Chair: Antonio Vita, MD, PhD, Università degli Studi di Brescia

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2025
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2026

Study Registration Dates

• First Submitted: June 2, 2026
• First Submitted That Met QC Criteria: June 2, 2026
• First Posted (Actual): June 8, 2026

Study Record Updates

• Last Update Posted (Actual): June 8, 2026
• Last Update Submitted That Met QC Criteria: June 2, 2026
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Bipolar and Related Disorders; Mental Disorders; Mood Disorders; Bipolar Disorder; Therapeutics
• Other Study ID Numbers: FULL-MINDSET

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No