Clinical trial NCT06105853: Neurobehavioral Profiles of Adaptive Stress Responses in Individuals With Alcohol Use Disorder
Official title: Towards Neurobehavioral Profiles and Models of Adaptive Stress Responses and Resilience in Individuals With Alcohol Use Disorder
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Alcohol Use Disorder
Stress Reaction
Social Stress
Craving
Relapse
Addiction, Alcohol
Risk Behavior
Keywords: stress
resilience
craving
sensitization
habituation
cortisol
ecological momentary assessment
alcohol use disorder
Lead sponsor: Central Institute of Mental Health, Mannheim
Sponsor class: OTHER
First posted: 2023-10-30
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: * longitudinal
* multimodal
* interventional
Primary purpose: TREATMENT

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

Eligibility criteria: Inclusion criteria are:

* 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 are:

* 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

Primary outcomes:
measure: Cortisol
timeFrame: Assessed at 4 time points at each examination day: after a 30-minute rest period [0:30 hours]; after the 15-minute stress intervention [0:45 hours]; after the 9-minute Barlab exposure [0:54 hours]; after the 75-minute fMRI [2:09 hours]
measure: Alcohol urges
timeFrame: Assessed at 4 time points at each examination day: after a 30-minute rest period [0:30 hours]; after the 15-minute stress intervention [0:45 hours], after the 9-minute Barlab exposure [0:54 hours]; after the 75-minute fMRI [2:09 hours]
measure: Alcohol craving
timeFrame: Assessed at 4 time points at each examination day: after a 30-minute rest period [0:30 hours]; after the 15-minute stress intervention [0:45 hours]; after the 9-minute Barlab exposure [0:54 hours]; after the 75-minute fMRI [2:09 hours]
measure: Subjective stress level
timeFrame: Assessed at 4 time points at each examination day: after a 30-minute rest period [0:30 hours]; after the 15-minute stress intervention [0:45 hours]; after the 9-minute Barlab exposure [0:54 hours]; after the 75-minute fMRI [2:09 hours]
measure: Neural alcohol-related cue-reactivity
timeFrame: at examination day: after 1:00 hour of the experimental procedure
measure: Neural inhibition processing
timeFrame: at examination day: after 1:00 hour of the experimental procedure
measure: Neural emotion processing
timeFrame: at examination day: after 1:00 hour of the experimental procedure
measure: Resting state activity
timeFrame: at examination day: after 1:00 hour of the experimental procedure
measure: Ecological momentary assessment
timeFrame: starting at the examination day until 6 weeks later; daily requests
Secondary outcomes:
measure: Blood pressure (systolic and diastolic)
timeFrame: Assessed at 4 time points at each examination day: after a 30-minute rest period [0:30 hours]; after the 15-minute stress intervention [0:45 hours]; after the 9-minute Barlab exposure [0:54 hours]; after the 75-minute fMRI [2:09 hours]
Other outcomes:
Locations:
city: Mannheim
country: Germany
facility: Central Institute of Mental Health
state: Baden-Württemberg
city: Mannheim
country: Germany
facility: Central Institute of Mental Health
Study officials:
affiliation: Central Institute of Mental Health
name: Patrick Bach, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Central Institute of Mental Health
name: Falk Kiefer, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Technical University Dresden
name: Clemens Kirschbaum, PhD
role: PRINCIPAL_INVESTIGATOR
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citation: 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.
citation: 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.