VR-based Avatar Therapy for Treatment of Auditory Hallucinations

VR-based Avatar Therapy for Treatment of Auditory Hallucinations in Patients With Schizophrenia 2023-SUD-3446

The primary aim of this study is to evaluate the safety and efficacy of AVATAR therapy, developed to address residual auditory hallucinations persisting despite medication in schizophrenia spectrum disorder. The intervention aims to reduce the intensity and frequency of these symptoms, as well as alleviate associated depressive and anxiety symptoms, using a virtual reality (VR)-assisted intervention developed for this purpose by the Danish company HEKA VR. The study will be a pre-post non-invasive, waiting list-controlled study, enrolling 30 patients from three clinical sites (Hungary, Spain, Poland).

The study centers around administering therapy based on VR over a 12-week period, comprising a total of 7 sessions. These sessions are conducted individually and last 50 minutes each. The psychotherapist leading the sessions adheres to a strict protocol defined by the method's developers.

During the intervention, VR technology is used to simulate the source of distressing auditory hallucinations. The therapist facilitates coping with these experiences externalized in this way through simulated conversations, supporting the development of more adaptive responses.

Patients undergo a comprehensive cross-sectional evaluation of their condition before and after the intervention, including assessments of symptom severity, quality of life, and their experience with the method. The intervention is conducted with constant monitoring for possible adverse effects.

Study Overview

• Status: Recruiting
• Conditions: Schizophrenia Spectrum and Other Psychotic Disorders; Hallucinations, Auditory
• Intervention / Treatment: Behavioral: AVATAR therapy

• Study Type: Interventional
• Enrollment (Estimated): 90
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Edit Vass, PhD; Phone Number: +36 30 360 9164; Email: vass.edit@semmelweis.hu
• Study Contact Backup: Name: Gábor Csukly, PhD; Email: csugab@yahoo.com

Study Locations

• Hungary
  • Budapest, Hungary
    • Recruiting
    • Semmelweis University
    • Contact: Edit Vass; Email: vass.edit@semmelweis.hu
    • Sub-Investigator: Gábor Csukly
    • Principal Investigator: Edit Vass
• Poland
  • Łódź, Poland
    • Not yet recruiting
    • Uniwersytet Medyczny w Łodzi
    • Principal Investigator: Jakub Kazmierski
    • Contact: Jakub Kazmierski; Email: jakub.kazmierski@umed.lodz.pl
• Spain
  • Barcelona, Spain
    • Active, not recruiting
    • University of Barcelona
  • Barcelona, Spain
    • Not yet recruiting
    • Unitat de Recerca del Parc Sanitari Sant Joan de Déu
    • Contact: Suzana Ochoa; Email: susana.ochoa@sjd.es
    • Sub-Investigator: Luciana Díaz-Cutraro
    • Principal Investigator: Suzana Ochoa

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Diagnosis of schizophrenia spectrum disorder according to DSM-5,
• Age 18 or older,
• The fluent use of the spoken language at the site (Hungarian/Spanish/Polish),
• Informed consent provided by the patient or their caregiver after being informed about the research procedure
• Stable medication dosage for at least 4 weeks prior to recruitment,
• Regular psychiatric follow-up,
• Experience of auditory hallucinations for at least three months (PANSS hallucination score of at least 3 points),
• Meeting the remission criteria described by Andreasen, except for the score related to auditory hallucinations

Exclusion Criteria:

• Inability to identify a single dominant voice that is the subject of the intervention,
• Lack of cooperation,
• Intellectual disability based on medical history,
• Regular substance abuse
• Central nervous system injury or neurological disease that affects cognitive performance,
• Suicidal risk
• Aversion to virtual reality,
• Severe visual impairment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: AVATAR therapy; All participants will initially undergo a 12-week waiting period (control period) starting from the initial screening at week 0. Baseline assessments will be conducted at week 12. Subsequently, participants will receive AVATAR therapy for 12 weeks. Post-therapy assessments will be conducted at week 24. Caregivers and therapists will also provide evaluations to gather additional insights into the therapy's impact

Behavioral: AVATAR therapy; In the initial phase of treatment, patients collaborate with therapists to visualize the source of their auditory hallucinations. Therapists adjust their voice to match the hallucinations, prompting patients to recall key statements for future sessions. Subsequent sessions involve dialogues with a computerized avatar. Using the altered voice, therapists interact in real-time through the avatar, engaging patients in role-playing. They alternate between the avatar and supportive therapist roles to empower patients with positive affirmations and discussions. Sessions last approximately 50 minutes, utilizing Oculus Rift VR headsets and noise-cancelling headphones to enhance immersion. HEKA VR software adjusts avatar proximity, and patients have the option to record dialogues for home use and sharing. Therapists receive bi-weekly supervision from HEKA VR-trained colleagues. Participants continue their regular medication prescribed by their psychiatrists alongside this experimental therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in symptom severity	Positive and Negative Syndrome Scale: Assesses overall symptom severity in schizophrenia spectrum disorders, including positive symptoms (e.g., hallucinations, delusions), negative symptoms (e.g., affective flattening, social withdrawal), and general psychopathology (e.g., anxiety, depression).The scale is administered through a semi-structured interview by trained clinicians. The minimum possible score for positive and negative symptoms is 7 points, and the maximum possible score is 49 points. For general symptomatology, the possible minimum score is 16 points, and the maximum score is 112 points. The overall score can range from 30-210. Higher scores indicate greater symptom severity.	Week 0, Week 12, Week 24
Change in severity of auditory hallucinations	Psychotic Symptom Rating Scales: Evaluates the severity of auditory hallucinations and associated delusions, including frequency, duration, loudness, and disruption. The scale is administered through a semi-structured interview by trained clinicians. The scale comprises 17 items of the mentioned specific dimensions of hallucinations and delusions, with each item being rated from 0 (absent) to 4 (severe). The total score range for the test is 0 to 68, where lower scores indicate reduced severity of hallucinatory experiences.	Week 0, Week 12, Week 24
Change in beliefs about voices in schizophrenia spectrum disorder	Beliefs About Voices Questionnaire-Revised: A self-report questionnaire designed to assess individuals' beliefs about auditory hallucinations (e.g.: how important the voices are to the individual, perceived control, emotional reactions elicited by the voices. The scale comprises 35 items, with each item being rated from 0 to 3. The total score range for the test is 0-105, where lower scores indicate reduced distress and improved coping with hallucinatory experiences.	Week 0, Week 12, Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in comorbidity (depression)	Calgary Depression Scale for Schizophrenia: Evaluates the severity of depressive symptoms in patients with schizophrenia. It is administered through a semi-structured interview, conducted by trained clinicians. The scale comprises 9 items, with each item being rated from 0 (absent) to 3 (severe). The total score range for the test is 0 to 27, where lower scores indicate reduced depressive symptoms and improved comorbidity management.	Week 0, Week 12, Week 24
Change in comorbidity (anxiety)	State-Trait Anxiety Inventory: A self-report questionnaire designed to assess anxiety levels in individuals. It distinguishes between two types of anxiety: State Anxiety: Refers to temporary feelings of anxiety that are situational and can fluctuate based on current circumstances. Trait Anxiety: Refers to a stable characteristic of an individual, reflecting a general tendency to respond with anxiety across various situations. The test consists of 40 items, with 20 items dedicated to measuring state anxiety and 20 items for trait anxiety. Respondents indicate how they feel on a scale from 1 (not at all) to 4 (very much so). Scores for each sub-scale can range from 20 to 80, with higher scores indicating greater levels of anxiety.	Week 0, Week 12, Week 24
Change in health-related quailty of life	EuroQol 5-Dimension 5-Level Scale: A standardised instrument for measuring health-related quality of life. It consists of two main components: the descriptive system and the visual analog scale. The descriptive system includes five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Respondents rate their health status in each dimension on a scale from 1 (no problems) to 5 (extreme problems), resulting in a profile that can be converted into a single index value. The visual analog scale allows individuals to rate their overall health on a scale from 0 (worst imaginable health) to 100 (best imaginable health).	Week 0, Week 12, Week 24
Change in subjective well-being	World Health Organisation Well-being Index: A brief self-report measure designed to assess subjective well-being and overall quality of life. Comprising five items, the index evaluates key aspects of emotional well-being over the past two weeks, including mood, energy, and general happiness. Respondents rate each item on a scale from 0 (at no time) to 5 (all of the time), resulting in a total score ranging from 0 to 25. Higher scores indicate better well-being and psychological health.	Week 0, Week 12, Week 24
Change in emotion regulation	Emotion Regulation Questionnaire: A self-report measure designed to assess individual differences in the habitual use of two emotion regulation strategies: cognitive reappraisal and expressive suppression. The questionnaire consists of 10 items, with respondents indicating their agreement on a scale from 1 (strongly disagree) to 7 (strongly agree). The possible total scores range from 10 to 70, with higher scores on cognitive reappraisal typically associated with better psychological outcomes, while higher scores on expressive suppression may be linked to various negative effects.	Week 0, Week 12, Week 24
Change in self-efficacy	General Self-Efficacy Scale: A self-report scale designed to assess perceived self-efficacy in coping with various stressors and challenges. The scale consists of 10 items that assess confidence in one's ability to handle different situations and overcome obstacles. Respondents rate each item on a scale from 1 (not at all true) to 4 (exactly true). Scores can range from 10-40, with higher scores indicate greater perceived self-efficacy.	Week 0, Week 12, Week 24

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient satisfaction	Patient Satisfaction Questionnaire: The questionnaire evaluates overall satisfaction with AVATAR therapy sessions by using open-ended questions and Likert scales. This questionnaire was created by the research team and adjusted specifically for this therapy.	Week 24
Therapist opinion	Therapist Opinion Questionnaire: The questionnaire assesses therapists' subjective opinions on the effectiveness and feasibility of AVATAR therapy by using open-ended questions and Likert scales. This questionnaire was created by the research team and adjusted specifically for this therapy.	Week 24
Caregiver opinion	Caregiver Opinion questionnaire: The questionnaire measures caregivers' perspectives on the impact of AVATAR therapy on patient well-being and daily functioning by using a questionnaire that includes open-ended questions and Likert scales. his questionnaire was created by the research team and adjusted specifically for this therapy.	Week 24
Cost-effectiveness analysis of the intervention	Conduct a thorough cost-effectiveness analysis within health economics, assessing the economic impact of the healthcare intervention under investigation through meticulous collection and analysis of healthcare utilization data, intervention-related costs, and health outcomes data. This will be achieved using a detailed demographic questionnaire, which includes information on disease duration (time since diagnosis), illness progression (such as frequency and duration of hospital stays), direct and indirect costs of care (such as medication costs, productivity loss, travel expenses, and caregiver burden), and patient living conditions (covering socio-economic status, employment, and living arrangements). The health economic evaluation will involve repeated administration of this questionnaire, ensuring adherence to established best practices and ethical standards	Week 0, Week 12, Week 24
Side effects	Simulator sickness questionnaire: A self-report tool used to assess symptoms of simulator sickness, which can occur during virtual reality. The questionnaire consists of 16 items that measure various symptoms associated with simulator sickness, including nausea, disorientation, and eye strain. Respondents rate the severity of each symptom on a scale from 0 (none) to 3 (severe). The total score ranges from 0-48, with higher scores indicating greater severity of simulator sickness.	After every therapy session between Week 13 and Week 23

Collaborators and Investigators

• Sponsor: Semmelweis University
• Collaborators: Fundació Sant Joan de Déu; Parc Sanitari Sant Joan de Déu; University of Barcelona; Uniwersytet Medyczny w Łodzi

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2024
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: July 2, 2024
• First Submitted That Met QC Criteria: July 10, 2024
• First Posted (Actual): July 17, 2024

Study Record Updates

• Last Update Posted (Actual): July 19, 2024
• Last Update Submitted That Met QC Criteria: July 17, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: Virtual reality; Schizophrenia spectrum disorder; AVATAR therapy; Auditory verbal hallucation
• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Perceptual Disorders; Schizophrenia; Psychotic Disorders; Hallucinations; Schizophrenia Spectrum and Other Psychotic Disorders
• Other Study ID Numbers: VR-AT-SCH 2023-SUD-3446

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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