Virtual Reality Cognitive-Affective Training for Opioid Use Disorder- A Phase 2 RCT

Digital Therapeutic Development of Virtual Cognitive-Affective Training for Opioid Use Disorder: A Phase 2 Randomized Controlled Trial

The goal of this clinical trial is to examine the usefulness of a virtual reality-delivered intervention for individuals with opioid use disorder who are taking medication. The main question it aims to answer is will people with opioid use disorder who receive the study intervention, Mindfulness-Oriented Recovery Enhancement in Virtual Reality (MORE-VR), have fewer days in which they use opioids than will people who just receive their usual treatment. Participants will be randomly assigned to either receive 8 weekly sessions of MORE-VR in addition to their usual treatment, or treatment as usual only. Researchers will compare these groups at the end of treatment and three months after treatment is over on number of days of opioid use and time until first opioid use lapse, as well as drug craving and mood.

This project is a Phase II, two-arm, parallel randomized controlled trial (RCT) of a virtual reality form of Mindfulness-Oriented Recovery Enhancement (MORE-VR) versus treatment as usual (TAU) for patients receiving medications for opioid use disorder (MOUD) to assess the efficacy of the MORE-VR system. Participants will be randomized (1:1) to either 8 weekly sessions of MORE-VR or TAU. Participants will be assessed at intake, post-treatment, and a 3 month post-treatment follow-up. The primary outcome assessed will be days of opioid use.

An 8-session version of Mindfulness-Oriented Recovery Enhancement (MORE) delivered by virtual reality. The treatment involves training in mindfulness, reappraisal, and savoring techniques to address OUD. Participants in this arm will also receive Treatment as usual (TAU) with medications for opioid use disorder (MOUD) such as buprenorphine or methadone plus any psychological counseling they are already receiving in their standard care.

Treatment as usual (TAU) with medications for opioid use disorder (MOUD) such as buprenorphine or methadone plus any psychological counseling they are already receiving in their standard care.

An 8-session version of Mindfulness-Oriented Recovery Enhancement (MORE) delivered by virtual reality. The treatment involves training in mindfulness,reappraisal, and savoring techniques to address OUD. Combination Product: Participants in this arm will also receive Treatment as usual (TAU) with medications for opioid use disorder (MOUD). Usual addictions treatment with medications such as buprenorphine or methadone plus psychological counseling.

Participants will receive their usual treatment for OUD, including medications such as buprenorphine or methadone and any counseling they might already be receiving

Days of opioid use assessed with the Timeline Followback method, ecological momentary assessments, and/or drug toxicology screen

Days of opioid use assessed with the Timeline Followback method, ecological momentary assessments, and/or drug toxicology screen

Number of days until opioid lapse assessed with the Timeline Followback method, ecological momentary assessments, and/or drug toxicology screen

Desires for Drug Questionnaire, range from 14 to 98, higher scores indicating more intense desires for drugs

0-10 numeric rating scale via ecological momentary assessment (0=no positive affect, 10=extremely strong positive affect).

0-10 numeric rating scale via ecological momentary assessment (0=no negative affect, 10=extremely strong negative affect).

A 20-item scale measuring both positive and negative affect, where each affective term is rated on a scale of 1 (not at all) to 5 (very much)

Emotional distress measured by the Depression Anxiety Stress Scale, range from 0 to 63, higher scores indicating worse distress.

World Health Organization Quality of Life Scale Quality of life measured by the World Health Organization Quality of Life Scale (WHO-5), scores ranging from 0 to 25, with higher scores indicating better quality of life.

For a subset of participants, we will asses change from baseline in neurophysiological response during lab-based task involving presentation of drug cues designed to measure cue-reactivity.

For a subset of participants, we will assess change from baseline in neurophysiological response during lab-based task involving presentation of emotional stimuli.

Inclusion Criteria: 18 years of age or older current DSM-5 OUD diagnosis prescribed medications for opioid use disorder (e.g., buprenorphine, methadone) Exclusion Criteria: completion of a standardized mindfulness intervention (e.g., MORE, MBRP, MBSR) active psychosis or suicidality reports, or is noted by clinical or study staff as showing cognitive impairment condition which might be contraindicated for VR use including seizure disorder, vertigo, severe motion sickness, recent concussion

Data will be available after publication of the primary, secondary, and mechanistic outcomes of the trial.