Virtual Reality (VR) NATURE - Alcohol Use Disorder (AUD)

Primary outcomes

1. Enrollment rates

   Time frame: Recruitment period (approximately 18 months)

   Recruitment will be quantified by enrollment rates relative to eligibility screenings.

2. Attendance at scheduled VR sessions

   Time frame: 4 weeks of VR

   Engagement will be assessed through attendance at scheduled VR sessions

3. Adherence to VR

   Time frame: 4 weeks of VR

   Adherence will be measured based on participants meeting the 12-session target.

4. Percentage of participants that complete the entire study duration -VR

   Time frame: 4 weeks of VR

   Retention will be evaluated through the percentage of participants who complete the entire study duration, targeting a benchmark of at least 8 of the 12 sessions.

5. Number of participants with documentation of informed consent completion

   Time frame: Recruitment period (Approximately 18 months)

6. The Virtual Reality Neuroscience Questionnaire (VRNQ)

   Time frame: 4 weeks of VR

   The modified scale for this project uses 10 questions that participants will answer about the VR experience, rated from 1 (extremely low or extremely difficult) to 7 (extremely high or extremely easy). The scores range from 10 to 70, with higher scores indicating greater experience.

7. Changes in depression measured by Patient Health Questionnaire-9 (PHQ-9)

   Time frame: Baseline, 4 weeks, 8 weeks

   This is a 9-item self-report measure developed to assess the presence and severity of depression symptoms aligned with the diagnostic criteria for major depressive disorder (MDD). Each item on the PHQ-9 reflects a specific depression symptom experienced over the past two weeks, including anhedonia, mood disturbances, fatigue, and suicidal ideation. Participants rate items on a 4-point Likert scale ranging from 0 ("not at all") to 3 ("nearly every day"), resulting in a total score range of 0 to 27. Clinical severity classifications include minimal (0-4), mild (5-9), moderate (10-14), moderately severe (15-19), and severe (20-27). A score of ≥10 is generally used as a cutoff for moderate depression, demonstrating optimal sensitivity and specificity.

8. Changes in anxiety measured by the Generalized Anxiety Disorder-7 (GAD-7)

   Time frame: Baseline, 4 weeks, 8 weeks

   This is a self-administered 7-item screening tool specifically designed to assess the frequency and severity of symptoms characteristic of generalized anxiety disorder (GAD) over the preceding two weeks. Symptoms measured include nervousness, worry, restlessness, irritability, and fearfulness, which are rated by respondents using a 4-point Likert scale ranging from 0 ("not at all") to 3 ("nearly every day"). Scores range from 0 to 21, with severity categories typically classified as minimal anxiety (0-4), mild anxiety (5-9), moderate anxiety (10-14), and severe anxiety (≥15). A cutoff score of ≥10 is commonly used to identify clinically significant anxiety.

9. Change on the Perceived stress scale (PSS-10)

   Time frame: Baseline, 4 weeks, 8 weeks

   This is a widely used psychological instrument for measuring the perception of stress. It comprises 10 items that assess how unpredictable, uncontrollable, and overloaded respondents find their lives. Each item is rated on a 5-point Likert scale ranging from "Never" (0) to "Very Often" (4). Items 4, 5, 7, and 8 are positively stated and are reverse scored. The total score ranges from 0 to 40, with higher scores indicating greater perceived stress. While there are no established cut-off scores, higher scores suggest higher levels of perceived stress.

10. Change on the Patient-Reported Outcomes Measurement Information System (PROMIS) Short Form v1.0 - Positive Affect

    Time frame: Baseline, 4 weeks, 8 weeks

    This is a psychometrically robust, 15-item measure specifically developed to assess positive emotional experiences or affective states over the past seven days. This PROMIS instrument focuses on capturing positive psychological constructs such as feelings of happiness, contentment, enthusiasm, and engagement with life. Participants rate each item using a 5-point Likert scale from 1 ("Not at All") to 5 ("Very Much"), with higher scores indicating greater levels of positive affect.

11. Change on the PROMIS Applied Cognition Short form v.1.0

    Time frame: Baseline, 4 weeks, 8 weeks

    This is a concise, validated 8-item measure designed to assess participants' perceived cognitive deficits, regardless of disease type. This PROMIS instrument focuses on participants' perceptions of their mental acuity, concentration, verbal and nonverbal memory, verbal fluency, and perceived changes in their cognitive functions. Participants rate each item on a 5-point Likert scale from 1 ("Not At All") to 5 ("Very Much"), with higher scores indicating greater cognitive dysfunction.

12. Change on the Ruminative Responses Scale

    Time frame: Baseline, 4 weeks, 8 weeks

    This is a validated and reliable 10-item scale that measures a participant's way of coping with repetitive and self-reflective moods. This is a shortened version of the Response Style Questionnaire and has been shortened to focus more on reflection and brooding, as compared to general depression. Participants rate each item from 1 ("Almost Never") to 4 ("Almost Always"), with higher scores indicating a greater level of rumination.

13. Change on the alcohol use disorders identification test (AUDIT)

    Time frame: Baseline, 4 weeks, 8 weeks

    This is a well-validated, standardized instrument developed by the World Health Organization for screening hazardous alcohol consumption, harmful drinking patterns, and potential alcohol dependence. This tool consists of 10 items assessing alcohol consumption frequency, quantity, binge drinking behaviors, dependence symptoms, and related negative consequences. Scores range from 0 to 40, with higher scores indicating greater alcohol use severity: scores of 8 or higher suggest hazardous drinking patterns, while scores of 20 or more indicate probable dependence.

14. Hardware and software-related issues

    Time frame: 4 weeks of VR

    The technical feasibility will be measured by tracking hardware and software-related issues, with acceptability ratings of ≥75%.

15. Change on the Drug Abuse Screening Test-10 (DAST-10)

    Time frame: Baseline, 4 weeks, 8 weeks

    This is a brief, validated self-report measure designed to identify problematic use of substances other than alcohol. It consists of 10 items assessing drug use frequency, associated consequences, interpersonal difficulties, and impairment resulting from substance use behaviors. Total scores range from 0 to 10, with higher scores indicating a greater severity of drug-related problems: scores of 3-5 suggest moderate risk, and scores of 6 or higher indicate substantial drug abuse risk warranting further clinical evaluation.

16. Qualitative interviews

    Time frame: 4 weeks

    Semi-structured qualitative interviews will be conducted individually with 10 randomly selected participants at 4 weeks to explore subjective experiences with the VR intervention. Each interview is anticipated to take approximately 30-40 minutes.

17. Study Dropout rates calculated as the proportion of enrolled participants that do not complete the Week 8 assessment visit (or the final planned study assessment)

    Time frame: Baseline - 8 weeks

    Dropout rate will be calculated as the proportion of enrolled participants who do not complete the Week 8 assessment visit (or the final planned study assessment) for any reason. The numerator is the number of participants who withdraw, are lost to follow-up, are discontinued by the study team, or otherwise fail to complete the Week 8 assessment. The denominator is the total number of participants enrolled and consented at baseline. Dropout will also be summarized by randomized arm. Higher values indicate worse retention (higher attrition).

18. Reasons for dropouts will be summarized as count and percentaged by overall by arm

    Time frame: Baseline - 8 weeks

    Drop-out reasons will be collected at the time of withdrawal, if possible, using a brief standardized exit reason will be coded into predefined categories and summarized as count and percentaged overall by arm [ VR- tolerability, time demands, other treatment factors, technology issues, safety concerns, cybersickness, lost to follow up, other] If multiple reasons are provided, the study team will identify a primary reason.