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

Alcohol Use Disorder Clinical Trial

— A03  

Official title:

Towards Neurobehavioral Profiles and Models of Adaptive Stress Responses and Resilience in Individuals With Alcohol Use Disorder

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06105853
• Other study ID #: TRR265-A03
• Status: Recruiting
• Phase: N/A
• Start date: December 1, 2023
• Est. completion date: June 30, 2027

Study information

• Verified date: January 2024
• Source: Central Institute of Mental Health, Mannheim
• Contact: Patrick Bach, MD, PhD
• Phone: +49 621 1703
• Email: patrick.bach[@]zi-mannheim.de
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: June 30, 2027
• Est. primary completion date: June 30, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Addiction, Alcohol
• Alcohol Drinking
• Alcohol Use Disorder
• Alcoholism
• Craving
• Fractures, Stress
• Relapse
• Risk Behavior
• Social Stress
• Stress Reaction

Intervention

Behavioral:
• 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).
• 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).
• Functional magnetic resonance imaging
Participants undergo a fMRI screening including three different behavioral tasks assessing alcohol cue reactivity, response inhibition, and emotion processing

Locations

Country	Name	City	State
Germany	Central Institute of Mental Health	Mannheim	Baden-Württemberg
Germany	Central Institute of Mental Health	Mannheim

Sponsors (1)

Lead Sponsor	Collaborator
Central Institute of Mental Health, Mannheim

Country where clinical trial is conducted

Germany, 

References & Publications (7)

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. — View Citation

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. — View Citation

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. — View Citation

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

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. — View Citation

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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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]
Primary	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]
Primary	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]
Primary	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]
Primary	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
Primary	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
Primary	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
Primary	Resting state activity	resting state connectivity measured with fMRI	at examination day: after 1:00 hour of the experimental procedure
Primary	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	Blood pressure (systolic and diastolic)	acquired with pressure sleeve (in mmHg)	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]