Integrating Virtual Reality, Neurofeedback, and Cognitive Behavioral Therapy for Auditory Verbal Hallucinations (Hybrid): Protocol of a Pilot, Unblinded, Single-Arm Interventional Study.

Background: Current treatments for schizophrenia and other psychotic disorders have limited efficacy, with high rates of nonresponse to "gold standard" treatments. New approaches are therefore urgently required.

Objective: The aims of this pilot study are to investigate the feasibility, acceptability, safety, and usability of Hybrid treatment (primary aim); and to explore Hybrid's treatment efficacy and engagement of treatment targets (secondary aim). The primary aim will be assessed via face-to-face user experience surveys on a (self-assessed) 5-point Likert scale (and qualitative open-ended questions) examining: (1) acceptability, (2) helpfulness, (3) engagement, and (4) perceived safety. We will also examine consent and completion rates, and the number of sessions attended. Our threshold for moving on to efficacy trials will be at least 70% of our participants to rate 3 and above (which corresponds to agree or strongly agree) that the intervention package was acceptable, feasible, and safe. The secondary aims will be assessed by observing whether individuals achieve self-directed modulation of high-β neurophysiological activity (neural target) and progression upwards through the VR-based exposure hierarchy (psychological target), and by assessing symptom change scores. This study developed a new treatment approach for auditory verbal hallucinations, a major symptom of psychotic disorders, that integrates advances in psychological therapy (cognitive behavioral therapy for psychosis), technology (virtual reality, VR), and neuroscience (electroencephalography-based neurofeedback).

Methods: Hybrid takes a "symptom capture" approach using individually tailored VR-based exposure exercises. Participants (N=10) will receive the intervention package weekly over 12 face-to-face sessions. Here, participants will be progressively exposed to symptom triggers and develop methods of downregulating neural activity associated with these symptoms (neurofeedback component) while concurrently receiving clinician-delivered cognitive behavioral therapy for psychosis.

Results: As of February 2025, Hybrid has commenced (unblinded) recruitment activities from Orygen clinical services in Northwestern Melbourne, Australia. A total of 75 individuals have been approached and 64 individuals have been prescreened (41 individuals were deemed eligible, 15 individuals were ineligible, and 8 individuals declined or did not respond to contact attempts) and 5 individuals have been included in the study. Of the 5 individuals who have commenced the Hybrid treatment, 4 are actively engaged in the program and 1 individual has withdrawn. We expect recruitment to conclude in July 2025 and for the results to be published in 2026.

Conclusions: The Hybrid study is piloting a novel approach that has the potential to address the shortcomings of current treatments for psychotic symptoms. If there is favorable evidence for the acceptability, feasibility, safety and usability of Hybrid, the study team will move on to efficacy trials.

Trial Registration: Australian New Zealand Clinical Trials Registry ACTRN12624000357550; https://tinyurl.com/24ey8hpy.

International Registered Report Identifier (irrid): PRR1-10.2196/63405.