Clinical trial NCT04125238: Increasing the Temporal Window in Individuals With Alcohol Use Disorder
Official title: Reinforcer Pathology 1A: Increasing the Temporal Window
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Alcohol Use Disorder
Keywords: Delay Discounting
Behavioral Economic Demand
Episodic Future Thinking
Self-Administration
Functional MRI
Alcohol Craving
Lead sponsor: Virginia Polytechnic Institute and State University
Sponsor class: OTHER
Collaborators: name: National Institute on Alcohol Abuse and Alcoholism (NIAAA)
name: McMaster University
name: Arizona State University
name: Carilion Clinic
name: University of Kentucky
First posted: 2019-10-14
Enrollment: 116
Sex: ALL
Minimum age (years): 21
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: Episodic future thinking (EFT) is based on the new science of prospection, which was first identified in a Science publication in 2007 and refers to pre-experiencing the future by simulation. Considerable evidence suggests that prospection is important for understanding human cognition, affect, motivation, and action. Individuals with damaged frontal areas, as well as individuals with alcohol use disorder (AUD), show deficits in planning prospectively. One systematic method to engender prospection is via EFT. EFT, as applied in our prior studies and in this proposal consists of having participants develop positive plausible future events that correspond to several future time frames (e.g., 2 weeks, 1 month, 3 months etc). For each of these timeframes participants are asked to concretize the events (e.g., What are you doing? Who will be there? What will you see, hear, smell, and feel?). We and others have used EFT to decrease delay discounting (DD) in individuals with AUD and smokers, as well as normal weight, overweight, and obese populations when compared to the control condition, control episodic thinking (CET). Consistent with reinforcer pathology, EFT also reduces alcohol valuation in the purchase task among individuals with AUD. However, no study to date has examined whether EFT reduces alcohol self-administration in the laboratory. Moreover, the neural correlates of EFT in AUD are also unknown. In these studies, we propose to test an intervention, EFT, which we hypothesize will decrease reinforcer pathology measures in a bar-like setting in the laboratory; that is, EFT will decrease delay discounting, as well as alcohol self-administration, demand, and craving compared to a control episodic thinking (CET) condition. Moreover, we hypothesize EFT will enhance activation in brain regions associated with prospection (e.g., hippocampus and amygdala) and the executive decision system (e.g., DLPFC). We will also examine the effect of EFT on real-world drinking.

Detailed description: In study 1, participants will be randomly assigned to experimental or control groups, stratified by AUDIT scores, SES, age and sex. Based on our 8 years of experience recruiting this population, we expect approximately 66% retention among eligible participants. Therefore, we will enroll approximately 107 participants in order to conclude with 64 completers. Participants will complete: a baseline assessment (S1), an alcohol self-administration session (S2 or S3), an fMRI session (S2 or S3). The alcohol self-administration session and the fMRI session will be completed in counterbalanced order. At the beginning of S2 and S3, participants in both groups will be prompted to generate positive events and related cues through a researcher-administered interview-based questionnaire. EFT group participants will be asked to think about and describe the most positive event that could realistically happen at each of 7 delays in the future (1 day, 1 week, 1 month, 3 months, 1 year, 5 years, and 25 years). In contrast, participants randomized to the CET condition, will be asked to think about and describe the most positive event that occurred at each of 7 time points from the recent past (last night from 7pm-10pm, yesterday between 4pm-7pm, yesterday between 1pm-4pm, yesterday from 10am-12pm, yesterday between 7am-10am, the night before last between 7pm-10pm, and evening before last between 4pm-7pm). For each time point, the participant will be asked to integrate the event and sensory information into concise textual and/or auditory cues to be used in subsequent behavioral tasks. Cue generation will occur prior to both self administration and fMRI sessions (S2 and S3) to maximize the relevancy of cues at both sessions.

In study 2, participants will complete two sessions and undergo a one-week baseline monitoring phase where they provide breath samples to assess for recent alcohol use and report their drinks per day. Following this baseline period, participants will complete an fMRI then be randomized to either the EFT or Control group. Participants will then complete two weeks of monitoring, where they provide a breath sample three times a day and report the number of drinks they consumed. Participants will then come back to the lab to generate new EFT/CET cues, then complete two more weeks of monitoring. After conclusion of the second intervention period, participants will complete a post intervention session and then a one month follow up one month after study completion.

Eligibility criteria: Inclusion Criteria:

* High-risk or harmful drinking (measured by AUDIT)
* 21-65 years of age
* Desire to quit or cut down on their drinking, but do not have proximate plans to enroll in treatment for AUD during the study period
* Report as one of their top three preferred drinks a beverage appropriate for the alcohol self-administration task (Study 1)

Exclusion Criteria:

* Moderate to severe DSM-5 criteria for substance-use disorders other than alcohol, nicotine, and/or marijuana
* Current diagnosis of any psychotic disorder
* History of seizure disorders or traumatic brain injury
* Contraindication for participation in the self-administration (Study 1) or MRI sessions (Studies 1 and 2)
* Current pregnancy or lactation.

Primary outcomes:
measure: Change in Delay Discounting (Studies 1 and 2)
timeFrame: At the first session (S1; baseline measures; Day 1), S2 session (occurs up to 7 days post S1), and S3 (occurs up to 7 days post S2).
measure: Change in Alcohol Demand (Studies 1 and 2)
timeFrame: At the first session (S1; baseline measures; Day 1), S2 session (occurs up to 7 days post S1), and S3 (occurs up to 7 days post S2).
measure: Change in Alcohol Craving (Studies 1 and 2)
timeFrame: At the first session (S1; baseline measures; Day 1), S2 session (occurs up to 7 days post S1), and S3 (occurs up to 7 days post S2).
measure: In-Laboratory Alcohol Consumption (Study 1)
timeFrame: Self-Administration session will occur at either Session 2 or Session 3 based on counterbalance assignment. S2 occurs up to 7 days post S1 and S3 occurs up to 7 days post S2.
measure: Neural activation during fMRI delay discounting task (Study 1)
timeFrame: fMRI session will occur at either Session 2 or Session 3 based on counterbalance assignment. S2 occurs up to 7 days post S1 and S3 occurs up to 7 days post S2.
measure: Neural activation during fMRI alcohol purchase task (Study 1)
timeFrame: fMRI session will occur at either Session 2 or Session 3 based on counterbalance assignment. S2 occurs up to 7 days post S1 and S3 occurs up to 7 days post S2.
measure: Change in alcoholic drinks per day (Study 2)
timeFrame: pre-post intervention
Secondary outcomes:
Other outcomes:
Locations:
city: Roanoke
country: United States
facility: Fralin Biomedical Research Institute at VTC
state: Virginia
Study officials:
affiliation: Fralin Biomedical Research Institute at VTC
name: Warren K Bickel, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Fralin Biomedical Research Institute at VTC
name: Stephen M LaConte, PhD
role: PRINCIPAL_INVESTIGATOR
References: