Clinical trial NCT05042180: Virtual Reality-Assisted Cognitive Behavioral Therapy for Alcohol Dependence (CRAVR)
Official title: Virtual Reality-Assisted Cognitive Behavioral Therapy for Alcohol Dependence: A Randomized Controlled Trial (CRAVR)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Alcohol Dependence, in Remission
Addiction, Alcohol
Keywords: Alcohol
Addiction
Virtual Reality
Exposure Therapy
Cognitive Behavioral Therapy
Lead sponsor: Psychiatric Centre Rigshospitalet
Sponsor class: OTHER
Collaborators: name: The Novavì outpatient clinics, Copenhagen
First posted: 2021-09-13
Enrollment: 102
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: single-blinded, randomized, controlled
Primary purpose: TREATMENT

Brief summary: The study is a single-blinded, randomized, controlled, 12 months clinical trial. The objective is to investigate the feasibility, effects and side-effects of virtual reality-assisted cognitive behavioral therapy (VR-CBT) vs. cognitive behavioral therapy (CBT) in patients with a diagnosis of alcohol dependence.

Detailed description: Recruitment of participants:

102 patients will be recruited from the Novaví outpatient clinics, where they will be informed orally and in writing about the research project and, if they are interested, an information meeting is booked. If patients show symptoms of abstinence, these are treated prior to the information meeting by doctors and nurses in Novaví. If the patient then wishes to participate and meets the inclusion criteria, informed consent is obtained and screening is performed using the questionnaires described later. Included patients will then be randomized to either:

1. Virtual reality-assisted cognitive behavioral therapy (VR-CBT)
2. Cognitive behavioral therapy (CBT) without VR (control group)

Screening:

At the screening sessions, patients' medical history is obtained, as well as their alcohol intake over the past 30 days recorded via Timeline Follow-Back (TLFB). Patients are also asked about previous alcohol dependence treatment and general information about psychosocial factors incl. education, work, marital status, and functional level using Global Assessment of functioning (GAF). In addition, alcohol-related problems are assessed using the Alcohol Users Identification Test (AUDIT), abstinence using the Clinical Institute Withdrawal Assessment of Alcohol Scale Revised (CIWA-Ar), intake of other drugs using the Drug User Identification Test (DUDIT), and alcohol craving using the Penn Alcohol Craving Scale (PACS). The Becks questionnaires, Depression Inventory 2 (BDI-II) and Beck's Anxiety Inventory (BAI), are included to assess the degree of anxiety and depression, and in addition, tests of mental function are performed using the Screening for Cognitive Impairment in Psychiatry (SCIP).

Intervention:

Included participants will in collaboration with their therapist schedule a standard course of treatment based on national guidelines from health authorities. After inclusion, participants are randomized to either:

1. 14 sessions of VR-CBT (Group A)
2. 14 sessions of CBT without VR (Group B, control group)

The participants in group A are exposed to VR-simulated high-risk situations filmed in a restaurant, a pub, at home, at a party or at the supermarket, to trigger alcohol cravings and other high-risk induced reactions of which the participants are subsequently trained to handle by trained therapists using CBT-based techniques.

The participants in group B receive the same treatment without VR exposure. The will be 4 weeks of weekly-biweekly treatment, followed by 20-21 weeks of treatment every 2-3 weeks, which is in line with the standard treatment in the Novaví outpatient clinics. The intervention deviates from standard treatment, as none of the participants receive pharmaceutical alcohol treatment during the treatment period (6 months) except for abstinence treatment if needed.

Randomization and blinding:

After screening a patient (ensuring that all inclusion criteria and no exclusion criteria are met) the patient is included. Participants are randomly allocated to either VR-CBT og CBT, 51 participants in each group. Randomization takes place in REDCap, which is a secure web application for building and managing surveys and databases. Age, sex and alcohol consumption are stratified at the time of inclusion ('heavy drinking days' and alcohol consumption - evaluated by TLFB). The technical setup of the randomization tool is performed in close collaboration with an expert in statistics, which ensures correct functionality before starting the experiment. After randomization, the therapist ensures that the participant receives the correct treatment and performs the alcohol craving assessment during each VR-CBT session unblinded using visual analog score (VAS). The study staff conducting the remaining data collections and the entire data analysis remain blinded until the database is opened at the end of the study. In situations where it is necessary to break the blind, it is possible to change the user rights in REDCap and gain access to the randomization tools. With the randomization tools, it is possible to detect the treatment (VR-CBT or CBT) based on study ID and all activities performed in REDCap are registered in the program.

Follow-up:

Each participant must attend a follow-up visit 3, 6, and 12 months from inclusion, where data collection will take place using the before mentioned questionnaires. The follow-up visit will be approx. 1 hour.

Statistical analysis:

All statistical analyzes are performed using the intention-to-treat principle, where all patients who have become randomized and has received a minimum of 1 session of VR-CBT (group A) or CBT without VR (group B), is included in the analysis. Missing data are implemented through the multiple imputation method and the analyzes are performed in the program "R" with alpha = 0.05 and 2-sided test. All continuous effect measures are analyzed using ANOVA from baseline to most recent measurement, and categorical data are analyzed using chi2 analysis. All data distributions will be assessed for normality by visual inspection of histogram and by Q-Q plots. If data is not normally distributed, log transformation is performed, and if this is not successful, non-parametric testing is used.

Eligibility criteria: Inclusion Criteria:

* Informed oral and written consent
* Meets criteria for alcohol dependence syndrome according to International Classification of Diseases (ICD) 10, WHO \& Diagnostic and Statistical Manual of Mental Disorder (DSM-5)
* Age 18 - 70 years old (both included)
* Minimum 5 'heavy drinking days' in the last month, which is defined as an alcohol intake above 60/48 grams or 5/4 items per. day for resp. men and women over the past 30 days

Exclusion Criteria:

* Other active substance use defined by DUDIT score\> 6 (for men)\> 2 (for women) and meet the criteria for other drug dependence according to ICD-10 (excluding nicotine)
* Does not speak or understand Danish
* Mental retardation or known severe psychiatric illness or other condition where it is assessed that will interfere with participation eg severely impaired vision or hearing.
* Medical alcohol treatment (disulfiram, acamprosate, naltrexone or nalmefen) within the latest 4 weeks and during the treatment period

Primary outcomes:
measure: Reduction in total alcohol consumption
timeFrame: Baseline, 6 months, 9 months, 12 months
Secondary outcomes:
measure: Change in heavy drinking days
timeFrame: Baseline, 6 months, 9 months, 12 months
measure: Change in Alcohol Users Identification Test (AUDIT) score
timeFrame: Baseline, 6 months, 9 months, 12 months
measure: Change in Drug User Identification Test (DUDIT) score
timeFrame: Baseline, 6 months, 9 months, 12 months
measure: Change in Penn Alcohol Craving Scale (PACS) score
timeFrame: Baseline, 6 months, 9 months, 12 months
measure: Screening for Cognitive Impairment in Psychiatry (SCIP) score
timeFrame: Baseline, 6 months, 9 months, 12 months
measure: Change in Global Assessment of functioning (GAF) score
timeFrame: Baseline, 6 months, 9 months, 12 months
measure: Becks Anxiety Inventory (BAI) score
timeFrame: Baseline, 6 months, 9 months, 12 months
measure: Becks Depression Inventory 2 (BDI-II) score
timeFrame: Baseline, 6 months, 9 months, 12 months
measure: Simulator Sickness Questionnaire (SSQ)
timeFrame: Each of the 14 treatment sessions over 6 months
measure: VR-induced craving on a visual analog scale (VAS)
timeFrame: Each of the 14 treatment sessions over 6 months
measure: Alcohol withdrawal symptoms
timeFrame: Evaluated at inclusion
measure: Qualitative assessment
timeFrame: After completion of a full treatment period of 6 months
Other outcomes:
Locations:
city: Copenhagen
country: Denmark
facility: Novavi ambulatorierne
state: Frederiksberg
Study officials:
References: