Personalized Approach Bias Modification in Heavy Drinking Veterans With Mild to Moderate Traumatic Brain Injury (TABM)

Personalized Approach Bias Modification to Reduce Heavy Drinking and Improve Cognitive Control in Veterans With Mild to Moderate Traumatic Brain Injury

The project will examine the neural associations of alcohol approach-bias and investigate the extent to which a neuroscience-based personalized cognitive training program will remediate alcohol approach-bias and improve recovery outcomes among heavy drinking Veterans with alcohol use disorder (AUD) and a history of mild-moderate traumatic brain injury (mmTBI). Alcohol approach-bias modification (ApBM) is a cognitive training intervention designed to interrupt and modify automatic approach processes in response to alcohol cues. Modification of alcohol approach-bias and reductions in heavy alcohol use can be expected to reduce behaviors of self-harm and violence, increase adherence to medical care, reduce drinking-related medical costs, and promote healthier relationships. The long-term goal is to demonstrate the efficacy of ApBM to promote recovery from AUD in Veterans with chronic mmTBI. The investigators also aim to identify neural mechanisms associated with ApBM and other neurocognitive predictors of successful recovery. The evidence garnered from this study will be useful to inform the development of other behavioral and pharmacological treatments for Veterans with AUD with a history of mmTBI.

Study Overview

• Status: Withdrawn
• Conditions: Alcohol Use Disorder; Mild-Moderate Traumatic Brain Injury
• Intervention / Treatment: Behavioral: Personalized VR Alcohol Approach Bias Modification (ApBM) Condition; Behavioral: Sham Condition

Detailed Description

This study is the first to test if Alcohol approach-bias modification (ApBM), delivered through virtual reality, as an add-on to outpatient treatment can reduce heavy alcohol use and improve neuro-cognitive outcomes among Veterans with mild to moderate traumatic brain injury (mmTBI) engaged in outpatient treatment for alcohol use disorder (AUD).

This will be a Phase II double-blind, randomized, sham-controlled clinical trial. Approximately 100 heavy drinking Veterans with alcohol use disorder (AUD) and a history of mild to moderate traumatic brain injury (mmTBI) will be randomized into the study to complete a 3-week of either personalized ApBM or sham training (9 training sessions). Immediately following the 3-week training, a post-intervention Week-4 assessment will be administered. The participants will also be re-assessed again at Week 12 as the last study visit.

The aims of the study are as follows:

Aim 1: Establish the efficacy of a personalized alcohol ApBM to promote recovery from AUD among heavy drinking Veterans with a history of mmTBI.

Aim 2: Evaluate alcohol ApBM related change in fMRI cue-induced craving outcomes of treatment response within Default Mode Network.

Aim 3: Assess alcohol approach bias modification-related improvement in cognitive executive functioning domains that typically show deficit in heavy drinking Veterans with mmTBI and replicate preliminary associations between executive function domains and alcohol approach bias.

• Study Type: Interventional
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94121-1563
      • San Francisco VA Medical Center, San Francisco, CA

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• A history of mild-moderate TBI, as defined by American Congress of Rehabilitation Medicine (ACRM), in the chronic, stable phase of recovery (>6 months from injury)
• Heavy drinking defined by NIH/NIAAA criteria (>7 drinks/week for women; >14 drinks/week for men) for at least one week in the last 90 days
• Moderate to severe criteria for current alcohol use disorder (AUD) by DSM-5
• Participants must also be engaged in VA outpatient AUD treatment and express a desire to reduce, stop, or maintain cessation of alcohol use

Exclusion Criteria:

• Unstable clinically significant psychiatric disorders or medical conditions that would create excessive risks, in the clinical judgment of the Principle Investigator

• Current or history of the following:

  • intrinsic cerebral tumors
  • demyelinating and neurodegenerative diseases
  • aneurysm
  • arteriovenous malformations
  • cerebrovascular or peripheral vascular disease
  • severe or penetrating traumatic brain injury
  • documented learning disabilities

  • surgical implantation of neurostimulators or cardiac pacemakers and any other MRI contraindications

    • These conditions/diseases are known to influence the neurocognitive and MR-derived neurobiological measures proposed in this application
• Female participant who is pregnant or actively attempting to conceive (to prevent any unnecessary exposure to high magnetic fields or radiofrequency energy to the unborn child)
• Concurrent participation in another clinical trial on AUD or TBI study
• Requiring acute medical detoxification from alcohol, based on a score of 12 or more on the Clinical Institute Withdrawal Assessment of Alcohol Scale (CIWA-AD)
• Legal mandate to participate in an alcohol treatment program
• Presence of severe TBI or penetrating head trauma
• Starting use of AUD treatment medications (disulfiram, naltrexone, or acamprosate) within the past 4 weeks (must be on AUD treatment for longer than 4 weeks)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Personalized VR Alcohol Approach Bias Modification (ApBM) Condition; The Personalized VR ApBM will consist of 9 cognitive training sessions, each session lasting approximately 20 minutes completed on separate days over 3 weeks. Each session requires the participant to respond to 240 visual stimuli using a push or pull motion as quickly as possible.	Behavioral: Personalized VR Alcohol Approach Bias Modification (ApBM) Condition; The Personalized VR ApBM will consist of 2D pictures representing alcohol or positive images (e.g., representing family or friends enjoying time together; sports, pets; travel and holidays, etc.) presented in a unique format in VR (e.g., landscape/portrait orientation), which will serve as the cue requiring a stimulus response. Participants are instructed to push the images away from them if they are presented in one format (e.g., landscape) and grab (using lever on VR controller) the images and pull towards themselves in response to a separate format (e.g., portrait pictures) across a virtual table. Each training session starts with 10 practice trials showing neutral objects (containers), followed by 240 training trials (120 alcohol and 120 non-alcohol trials). Training effect is achieved by altering the contingency of push vs. pull by image type (alcohol vs. positive).; Other Names: ApBM Training
Sham Comparator: Sham Condition; Sham training will consist of 9 cognitive training sessions, each session lasting approximately 20 minutes completed on separate days over 3 weeks. Each session requires the participant to respond to 240 visual stimuli using a push or pull motion as quickly as possible.	Behavioral: Sham Condition; Sham training is identical to ApBM, except the contingency of each orientation (e.g., portrait or landscape) representing a push vs. a pull is altered to diminish training effect.; Other Names: Sham Training

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent of Heavy Drinking Days	The primary endpoint is percent of heavy drinking days during the 90 days post-randomization into treatment. A heavy drinking day is defined using NIH/NIAAA criteria, drinking more than 4 drinks a day for men and more than 3 drinks a single day for women.	90 days post-randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cue-induced fMRI BOLD-signal craving activation contrasts	BOLD-signal craving activation contrasts (alcohol cues > neutral cues) in amygdala, nucleus accumbens, and posterior cingulate cortex.	Week 4 - The week following completion of cognitive training.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cognitive flexibility	Cognitive flexibility is derived from the Delis-Kaplan Executive Function System (D-KEFS) Trail Making Test Number-Letter Sequencing Condition 4 and Design Fluency Condition 3. Raw scores from these two measures are converted to z-scores based on standard norms. A cognitive flexibility summary score is calculated by averaging the z-scores of the individual constituent measures.	Week 4 - The week following completion of cognitive training.

Collaborators and Investigators

• Sponsor: VA Office of Research and Development
• Investigators: Principal Investigator: David L Pennington, San Francisco VA Medical Center, San Francisco, CA

Study record dates

Study Major Dates

• Study Start (Actual): June 24, 2024
• Primary Completion (Actual): June 24, 2024
• Study Completion (Actual): June 24, 2024

Study Registration Dates

• First Submitted: April 18, 2024
• First Submitted That Met QC Criteria: April 18, 2024
• First Posted (Actual): April 24, 2024

Study Record Updates

• Last Update Posted (Actual): June 27, 2024
• Last Update Submitted That Met QC Criteria: June 26, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Keywords: Cognitive Training; Alcohol Use Disorder; Alcohol-Related Disorders; Mental Disorders; Cognitive Bias Modification; Brain Injury, Traumatic
• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Drinking Behavior; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Alcohol-Related Disorders; Substance-Related Disorders; Craniocerebral Trauma; Trauma, Nervous System; Alcohol Drinking; Alcoholism; Brain Injuries; Wounds and Injuries; Brain Injuries, Traumatic
• Other Study ID Numbers: NURA-009-23F; 1I01CX002715-01A1 (Other Grant/Funding Number: Clinical Science Research & Development)

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
• product manufactured in and exported from the U.S.: No