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

NCT06105853 | Recruiting

• 1 other identifier: TRR265-A03
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 2

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.

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

Outcome Measures

Primary Outcomes (9)

• Cortisol

  Cortisol levels measured in saliva as a stress marker (in nmol/l)

  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]

• Alcohol urges

  self-report questionnaire: "Alcohol Urge Questionnaire (AUQ)" with Bohn et al. 1995; containing 8 items; each item will be rated on a 7-point-Likert-Scale from 1 "not true at all" (minimum) to 7 "completely true" (maximum); sum score is defined as outcome and higher outcome reflects higher alcohol urges

  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]

• Alcohol craving

  self-report "How strong is your craving for alcohol?"; containing 1 item; reported on a visual analogue scale ranging from 0 ("no craving") to 100 ("very strong craving")

  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]

• Subjective stress level

  self-report questionnaire: "Primary Appraisal Secondary Appraisal (PASA)"; Gaab, 2009; containing 16 items; each item will be rated on a 6-Point-Scale from 1 ("completely wrong") to 6 ("quite right"); sum score is defined as outcome and higher outcome reflects a higher subjective stress level

  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]

• Neural alcohol-related cue-reactivity

  percent signal change from baseline condition (i.e. fixation cross), measured with fMRI; paradigm Vollstädt-Klein et al. 2010; \[percent signal change is not a change over time; it is measured during one experimental session\]; presentation of neutral and alcoholic (categories: beer, wine, spirits) stimuli in 20 blocks (blocked design; one block à 5 stimuli each presented for 4 seconds), after each block participants had to rate their craving: "I have alcohol craving." from 0 ("no craving at all") to 100 ("severe craving"), maximum rating duration is 10 seconds, following the rating a fixation cross was presented (10 seconds), total task duration: 12 minutes

  at examination day: after 1:00 hour of the experimental procedure

• Neural inhibition processing

  percent signal change from baseline condition (i.e. fixation cross), measured with fMRI; stop-signal reaction time task (Fauth-Buhler et al. 2012) \[percent signal change is not a change over time; it is measured during one experimental session\]; conduction of a stop-signal task of 600 trials (500 go-trials and 100 stop trials, participant have to respond as quickly as possible by pressing the left or right button according to the arrow direction, between the trials a fixation cross was presented (for 700 milliseconds to 1100 milliseconds), total task duration: 19 minutes

  at examination day: after 1:00 hour of the experimental procedure

• Neural emotion processing

  percent signal change from baseline condition (i.e. fixation cross), measured with fMRI; faces task (Hariri et al. 2002) \[percent signal change is not a change over time; it is measured during one experimental session\]; participants were exposed to faces with varying emotions and forms (geometric shapes as a sensorimotor control task) and had to match one of two simultaneously presented images with an identical target image, a total of nine blocks (four with faces, five controls) each lasting 32 seconds and a total duration of about five minutes

  at examination day: after 1:00 hour of the experimental procedure

• Resting state activity

  resting state connectivity measured with fMRI

  at examination day: after 1:00 hour of the experimental procedure

• Ecological momentary assessment

  Self-report ratings of: Real-life alcohol craving with the item "How strong is your current alcohol craving?", rating with a 7-Point-Likert-Scale from 1 "no craving" to 7 "extreme craving"; of stress exposure with the item "How strong is your current level of stress?", rating with a 7-Point-Likert-Scale from 1 "not at all" to 7 "very stressed"; of alcohol consumption with the item "Remember yesterday: Which and how many alcoholic drinks did you consume?", a short-list with listed drinks and amounts will open from which participants can choose; and of stress coping with the item "How did you deal with unpleasant situations since the last prompt?", rating with a 5-Point-Likert-Scale from 1 "not at all" to 5 "excellent"

  starting at the examination day until 6 weeks later; daily requests

Secondary Outcomes (1)

• Blood pressure (systolic and diastolic)

  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]

Study Arms (1)

Experimental

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

Behavioral: Trier Social Stress Test; Behavioral: Barlab Cue-Exposure; Behavioral: Functional magnetic resonance imaging

Interventions

Trier Social Stress Test BEHAVIORAL

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

Experimental

Barlab Cue-Exposure 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).

Experimental

Functional magnetic resonance imaging BEHAVIORAL

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

Experimental

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Central Institute of Mental Health, Mannheim: lead

Study Sites (2)

Central Institute of Mental Health

Mannheim, Baden-Wurttemberg, 68159, Germany

RECRUITING

Central Institute of Mental Health

Mannheim, 68159, Germany

RECRUITING

Related Publications (7)

• Fauth-Buhler M, de Rover M, Rubia K, Garavan H, Abbott S, Clark L, Vollstadt-Klein S, Mann K, Schumann G, Robbins TW. Brain networks subserving fixed versus performance-adjusted delay stop trials in a stop signal task. Behav Brain Res. 2012 Nov 1;235(1):89-97. doi: 10.1016/j.bbr.2012.07.023. Epub 2012 Jul 20.

  PMID: 22820235 BACKGROUND

• Kirschbaum C, Prussner JC, Stone AA, Federenko I, Gaab J, Lintz D, Schommer N, Hellhammer DH. Persistent high cortisol responses to repeated psychological stress in a subpopulation of healthy men. Psychosom Med. 1995 Sep-Oct;57(5):468-74. doi: 10.1097/00006842-199509000-00009.

  PMID: 8552738 BACKGROUND

• Bohn MJ, Krahn DD, Staehler BA. Development and initial validation of a measure of drinking urges in abstinent alcoholics. Alcohol Clin Exp Res. 1995 Jun;19(3):600-6. doi: 10.1111/j.1530-0277.1995.tb01554.x.

  PMID: 7573780 BACKGROUND

• Gaab J. PASA - Primary Appraisal Secondary Appraisal. Verhaltenstherapie. 2009; 114-115.

  BACKGROUND

• Hariri AR, Tessitore A, Mattay VS, Fera F, Weinberger DR. The amygdala response to emotional stimuli: a comparison of faces and scenes. Neuroimage. 2002 Sep;17(1):317-23. doi: 10.1006/nimg.2002.1179.

  PMID: 12482086 BACKGROUND

• 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.

  PMID: 20670348 BACKGROUND

• 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.

  PMID: 34132011 BACKGROUND

MeSH Terms

Conditions

Alcoholism; Fractures, Stress; Recurrence; Risk-Taking; Substance-Related Disorders

Interventions

Psychological Tests

Condition Hierarchy (Ancestors)

Alcohol-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Fractures, Bone; Wounds and Injuries; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Behavioral Disciplines and Activities

Study Officials

• Patrick Bach, MD, PhD

  Central Institute of Mental Health

  PRINCIPAL INVESTIGATOR

• Falk Kiefer, MD

  Central Institute of Mental Health

  PRINCIPAL INVESTIGATOR

• Clemens Kirschbaum, PhD

  Technical University Dresden

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Patrick Bach, MD, PhD

CONTACT

+49 621 1703; patrick.bach@zi-mannheim.de

Judith Zaiser

CONTACT

+49 621 1703; judith.zaiser@zi-mannheim.de

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: * longitudinal * multimodal * interventional

Study Record Dates

• First Submitted: September 14, 2023
• First Posted: October 30, 2023
• Study Start: December 1, 2023
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): June 30, 2027
• Last Updated: April 29, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

DE (2)