Neurobehavioral Profiles of Adaptive Stress Responses in Individuals With Alcohol Use Disorder

NCT ID: NCT06105853

Last Updated: 2025-04-29

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 100 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-12-01
• Study Completion Date: 2027-06-30

Brief Summary

The goal of this observational study is to investigate longitudinal stress response profiles and adaptive versus non-adaptive stress responses in alcohol use disorder. The main questions the projects aims to answer are:

What are the neurobehavioral underpinnings of adaptive stress responses and resilience to repeated stress exposure with regards to:

• alcohol craving?
• alcohol use?
• their modulation by prior stress exposure, social interactions, coping strategies and individual health behavior?

Participants will:

• be exposed to an established experimental stress-induction protocol, the Trier Social Stress Test
• be exposed to their favorite drink in a bar lab environment
• be assessed using fMRI to determine their neural alcohol cue reactivity, response inhibition, and emotion processing
• conduct an ambulatory phase to assess stressors, alcohol craving, substance use and details on social interactions, health behavior and coping strategies using ecological momentary assessment tools.

Detailed Description

The main objective of the study is to identify longitudinal profiles and models of adaptive stress responses and stress resilience in individuals with alcohol use disorder (AUD) and understand how stress and different responses to it influence alcohol craving and alcohol use trajectories over time. To achieve these goals, the investigators will examine habituation vs. sensitization of cortisol responses to repeated experimental stress exposure in individuals with AUD, as an established experimental model to studying adaptive vs. non-adaptive stress responses in the framework of an experimental set-up including an initial rest period (30 minutes), followed by the Trier Social Stress Test (15 minutes), exposure to the favorite drink in a bar environment (9 minutes) and functional magnetic resonance imaging (75 minutes) assessing A) neural alcohol cue-reactivity, B) inhibition performance during a Stop Signal Task, C) emotion processing during a face-matching task and D) resting state connectivity. The investigators also seek to characterize the neurobehavioral underpinnings of sensitized vs. habituated responses to repeated stress exposure, using an established alcohol cue-reactivity fMRI paradigm, and determine the impact of sensitized vs. habituated stress responses on physiological and subjective stress markers, alcohol craving, alcohol use, as well as their modulation by prior stress exposure, social support, drinking goals and individual health behavior with a focus on potentially modifiable factors that could serve as targets for future ecological momentary interventions. This setup will be repeated on a second examination day.

In addition, the investigators aim to assess whether the observed habituation vs. sensitization phenotypes to repeated stress exposure translate into everyday-life of the respective individual and predict adaptive vs. non-adaptive stress responses. To this end, the investigators will acquire ambulatory assessments with high temporal resolution over six weeks, including detailed mapping of exposure to micro- and macro-stressors, drinking motifs, alcohol craving, alcohol use and data on factors that potentially modify the association between stress and alcohol use, such as social interactions, stress coping strategies, drinking goals and individual health behavior (e.g., sleep, physical activity) to assess whether the observed habituation vs. sensitization phenotypes to repeated stress exposure translate into everyday-life of the respective individual and predict real-life stress responses and alcohol use.

Study flow:

Screening (telephone): Assessing study eligibility

Experimental study visit 1: Rest period (30 minutes) - Trier Social Stress Test (15 minutes) - Alcohol cue exposure (9 minutes) - fMRI (75 minutes)

Experimental study visit 2: Repetition of setup from 'experimental study visit 1'

Following six weeks: Ambulatory phase (smartphone tool) with daily requests regarding stressors, alcohol craving and consumption as well as health behavior

Conditions

Alcohol Use Disorder; Stress Reaction; Social Stress; Craving; Relapse; Addiction, Alcohol; Risk Behavior

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Experimental

All participants will be exposed to the Trier Social Stress Test, followed by an alcohol cue-exposure in a barlab environment and functional magnetic resonance imaging assessing neural alcohol cue-reactivity, inhibition performance, emotion processing and resting state functional connectivity twice on two consecutive days.

Interventions:

Behavioral: Trier Social Stress Test

Behavioral: Cue-Exposure to the favorite drink in a barlab setting

Group Type: EXPERIMENTAL

Trier Social Stress Test

Intervention Type: BEHAVIORAL

Test to induce high levels of acute social stress, including actors, representing the judging panel, and a faked exam situation (15 minutes duration).

Barlab Cue-Exposure

Intervention Type: BEHAVIORAL

Participants are exposed to a bar situation with their individual favorite alcohol presented. They handle their favorite alcoholic drink and water (9 minutes duration).

Functional magnetic resonance imaging

Intervention Type: BEHAVIORAL

Participants undergo a fMRI screening including three different behavioral tasks assessing alcohol cue reactivity, response inhibition, and emotion processing

Interventions

Trier Social Stress Test

Test to induce high levels of acute social stress, including actors, representing the judging panel, and a faked exam situation (15 minutes duration).

Intervention Type: BEHAVIORAL

Barlab Cue-Exposure

Participants are exposed to a bar situation with their individual favorite alcohol presented. They handle their favorite alcoholic drink and water (9 minutes duration).

Intervention Type: BEHAVIORAL

Functional magnetic resonance imaging

Participants undergo a fMRI screening including three different behavioral tasks assessing alcohol cue reactivity, response inhibition, and emotion processing

Intervention Type: BEHAVIORAL

Eligibility Criteria

Inclusion Criteria

• age between 16 and 65 years
• meeting at least 2 criteria of an alcohol use disorder according to the Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) (DSM-5), yet without the need for a therapeutic intervention
• fluency in German
• able to understand the study procedures and give informed consent
• willingness to use a study smartphone

Exclusion Criteria

• current use of drugs or medications that interact with the central nervous system or the glucocorticoid system
• contraindications for magnetic resonance imaging
• medical history of bipolar disorder, psychotic disorder, schizophrenia or schizophrenic spectrum disorder, or substance use disorder other than alcohol, nicotine, or cannabis
• medical history of severe head injury or other severe central nervous system disorders or other severe somatic disorders (e.g. liver cirrhosis)
• pregnancy

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Central Institute of Mental Health, Mannheim

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Patrick Bach, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Central Institute of Mental Health

Falk Kiefer, MD

Role: PRINCIPAL_INVESTIGATOR

Central Institute of Mental Health

Clemens Kirschbaum, PhD

Role: PRINCIPAL_INVESTIGATOR

Technical University Dresden

Locations

Central Institute of Mental Health

Mannheim, Baden-Wurttemberg, Germany

Site Status: RECRUITING

Central Institute of Mental Health

Mannheim, , Germany

Site Status: RECRUITING

Countries

Germany

Central Contacts

Patrick Bach, MD, PhD

Role: CONTACT

patrick.bach@zi-mannheim.de

+49 621 1703 ext. 0

Judith Zaiser

Role: CONTACT

judith.zaiser@zi-mannheim.de

+49 621 1703 ext. 0

Facility Contacts

Patrick Bach, MD

Role: primary

patrick.bach@zi-mannheim.de

+496211703 ext. 0

References

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Reference Type: BACKGROUND

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Reference Type: BACKGROUND

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Reference Type: BACKGROUND

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Vollstadt-Klein S, Wichert S, Rabinstein J, Buhler M, Klein O, Ende G, Hermann D, Mann K. Initial, habitual and compulsive alcohol use is characterized by a shift of cue processing from ventral to dorsal striatum. Addiction. 2010 Oct;105(10):1741-9. doi: 10.1111/j.1360-0443.2010.03022.x.

Reference Type: BACKGROUND

PMID: 20670348 (View on PubMed)

Bach P, Reinhard I, Koopmann A, Bumb JM, Sommer WH, Vollstadt-Klein S, Kiefer F. Test-retest reliability of neural alcohol cue-reactivity: Is there light at the end of the magnetic resonance imaging tube? Addict Biol. 2022 Jan;27(1):e13069. doi: 10.1111/adb.13069. Epub 2021 Jun 15.

Reference Type: BACKGROUND

PMID: 34132011 (View on PubMed)

Other Identifiers

TRR265-A03

Identifier Type: -

Identifier Source: org_study_id