Stress-related Predictor Profiles in Human Addiction

Stress-related Predictor Profiles for Craving and Relapse in Human Addiction

Long-term aim is the definition of a setup of mobile sensors and their integration in a mobile infrastructure that allows the prediction of stress related alcohol intake in an ambulatory setting. Here, we aim to identify stress- and alcohol cue-related physiological markers in a lab experiment to assess interactions between acute psychological vs. physical stress exposure and alcohol cue-exposure regarding their effects on measures relevant for the development and maintenance of Alcohol Use Disorder (AUD). Further, we aim to identify neural correlates in brain circuits of motivational, cognitive, and affective processing. In addition to applying established stress-related markers, we will integrate innovative sensor-based measures.

Study Overview

• Status: Completed
• Conditions: Risk Behavior; Addiction; Alcohol Use Disorder; Craving; Relapse; Stress Reaction; Social Stress
• Intervention / Treatment: Behavioral: Trier Social Stress Test; Behavioral: Barlab-Exposure; Behavioral: Reading Newspaper; Behavioral: Ergometer

Detailed Description

In patients with Alcohol Use Disorder (AUD) stress exposure is known to affect craving, cue-reactivity and relapse risk. Here, we aim to identify stress- and alcohol cue-related physiological markers in a lab experiment to assess interactions between acute psychological vs. physical stress exposure and alcohol cue-exposure regarding their effects on (1) alcohol craving and related markers (attentional bias to alcohol-cues, implicit association task, neural cue-reactivity), (2) their predictive capacity for future alcohol intake, (3) the identification their neural correlates in brain circuits of motivational, cognitive, and affective processing. In addition to applying established stress-related markers (cortisol in saliva, heart-rate variability, systolic blood pressure and electrodermal activity), (4) we will integrate portable sensors (wearables) to allow a future integration in ambulatory assessments and to test innovative measures currently under investigation (e.g. voice stress analysis) to identify whether these additional parameters increase the predictive significance. Our long-term aim is the definition of a setup of mobile sensors and their integration in a mobile infrastructure that allows the prediction of stress related alcohol intake in an ambulatory setting.

• Study Type: Interventional
• Enrollment (Actual): 121
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Germany
  • Baden-Württemberg
    • Mannheim, Baden-Württemberg, Germany, 68159
      • Klinik für Abhängiges Verhalten, Zentralinstitut für Seelische Gesundheit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Alcohol-use disorder according to 2 DSM-V criteria not requiring detoxification: AUD subjects with mild AUD will fulfill at least 2 and not more than 5 diagnostic criteria; a second group of AUD subjects will fulfill 4-5 criteria for moderate AUD
• sufficient ability to communicate with the investigators, to answer questions in oral and written form
• fully informed consent
• written informed consent

Exclusion Criteria:

• withdrawal of the declaration of consent
• Pregnancy
• Using hormonal contraceptives
• Perimenopausal/ postmenopausal
• positive urin drug screening (cannabis, amphetamine, opiates, benzodiazepines, cocaine)
• Lifetime history of DSM-5 bipolar disorder, schizophrenia or schizophrenia spectrum disorder, or substance dependence other than alcohol or nicotine or cannabis dependence.
• Current threshold DSM-5 diagnosis of major depressive disorder, or presence of suicidal intention
• History of severe head trauma or other severe central nervous system disorder (e.g., dementia, Parkinson's disease, multiple sclerosis)
• Current use of medications or drugs known to interact with the CNS within at least four half-lives post last intake

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Control; Participants reads newspaper before Barlab-Exposure	Behavioral: Barlab-Exposure; Participants are exposed to a bar situation with different sorts of alcohol available. They sniff at water and at one alcoholic drink.; Behavioral: Reading Newspaper; Participants read newspaper
Experimental: Experimental 1 (Distress); Participants undergo the Trier Social Stress Test before Barlab-Exposure	Behavioral: Trier Social Stress Test; Test to induce high levels of acute social stress, including actors and a faked exam situation; Behavioral: Barlab-Exposure; Participants are exposed to a bar situation with different sorts of alcohol available. They sniff at water and at one alcoholic drink.
Experimental: Experimental 2 (Eustress); Participants ride an ergometer before Barlab-Exposure	Behavioral: Barlab-Exposure; Participants are exposed to a bar situation with different sorts of alcohol available. They sniff at water and at one alcoholic drink.; Behavioral: Ergometer; Riding ergometer

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
change in heart rate	heart rate acquired with ear clip (continuous time series)	at examination day: continuous measurement throughout the whole experiment (except during MRI scanning); duration around 2 hours; starting 1 hour 50 minutes after arrival of the proband
change in electrodermal activity	time series acquired with body sensor	at examination day: continuous measurement throughout the whole experiment (except during MRI scanning); duration around 2 hour; starting 1h 50min after arrival of the proband
neural inhibition processing	% signal change, measured with fMRI; stop-signal reaction time task (Fauth-Buhler et al. 2012) [% signal change is not a change over time; it is measured during one experimental session]	at examination day: measured directly after the behavioral tasks at the end of the lab experiment
neural emotion processing	% signal change, measured with fMRI; faces task (Hariri et al. 2002) [% signal change is not a change over time; it is measured during one experimental session]	at examination day: measured directly after the behavioral tasks at the end of the lab experiment
resting state activity	resting state connectivity measured with fMRI	at examination day: measured directly after the behavioral tasks at the end of the lab experiment
attentional bias to alcohol cues	measured with reaction time differences (in milliseconds) using the dotprobe-task (Vollstädt-Klein et al. 2009) [reaction time differences is not a change over time; it is measured during one experimental session]	at examination day: measured directly after the stress task / newspaper reading; before "implicit alcohol association" and MRI session
implicit alcohol association	measured with reaction time differences (in milliseconds) using the implicit association task (Wiers et al. 2016) [reaction time differences is not a change over time; it is measured during one experimental session]	at examination day: measured after the stress task / newspaper reading, directly after the "attentional bias to alcohol cues" ; before MRI session
change in level of cortisol	cortisol measured in saliva as a stress marker	at examination day: 6 time points measured throughout the whole experiment (except during MRI scanning); at hours:minutes 2:20, 2:50, 3:20, 3:50, 4:50, 5:05 after arrival of the proband
change in voice stress pattern	audio file of participants' voice for voice stress pattern analysis will be recorded. From this a multivariate measure (i.e. multivariate vector) will be acquired (including frequency, loudness etc.)	at examination day: 6 time points measured throughout the whole experiment (except during MRI scanning); at hours:minutes 2:20, 2:50, 3:20, 3:50, 4:50, 5:05 after arrival of the proband
change in alcohol craving	self-report "How strong is your craving for alcohol?": reported on a visual analogue scale ranging from 0 to 100	at examination day: 6 time points measured throughout the whole experiment (except during MRI scanning); at hours:minutes 2:20, 2:50, 3:20, 3:50, 4:50, 5:05 after arrival of the proband
change in heart rate variability	heart rate variability acquired with ear clip (continuous time series)	at examination day: continuous measurement throughout the whole experiment (except during MRI scanning); duration around 2 hour; starting 1 hour 50 minutes after arrival of the proband
change in blood pressure (systolic and diastolic)	acquired with pressure sleeve	at examination day: 6 time points measured throughout the whole experiment (except during MRI scanning); at hours:minutes 2:20, 2:50, 3:20, 3:50, 4:50, 5:05 after arrival of the proband
neural alcohol-related cue-reactivity	% signal change, measured with fMRI; paradigm Vollstädt-Klein et al. 2010; [% signal change is not a change over time; it is measured during one experimental session]	at examination day: measured directly after the behavioral tasks at the end of the lab experiment
fMRI	neural alcohol-related cue-reactivity, stop-signal reaction time task, emotion processing and resting state fMRI	at examination day: measured directly after the behavioral tasks at the end of the lab experiment
change in alcohol urges	self-report questionnaire: "Alcohol Urge Questionnaire (AUQ)"; Bohn et al. 1995	at examination day: 6 time points measured throughout the whole experiment (except during MRI scanning); at hours:minutes 2:20, 2:50, 3:20, 3:50, 4:50, 5:05 after arrival of the proband

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
alcohol consumption	self-report using the instrument Form90 (Scheurich et al. 2005)	12 months follow-up

Collaborators and Investigators

• Sponsor: Central Institute of Mental Health, Mannheim
• Collaborators: Project Group for Automation in Medicine and Biotechnology PAMB, Mannheim
• Investigators: Principal Investigator: Falk Kiefer, Prof., Central Institute of Mental Health, Mannheim

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2019
• Primary Completion (Actual): September 30, 2022
• Study Completion (Actual): July 8, 2023

Study Registration Dates

• First Submitted: November 26, 2018
• First Submitted That Met QC Criteria: January 16, 2019
• First Posted (Actual): January 22, 2019

Study Record Updates

• Last Update Posted (Actual): September 15, 2023
• Last Update Submitted That Met QC Criteria: September 14, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Pathologic Processes; Alcohol-Related Disorders; Substance-Related Disorders; Fractures, Bone; Wounds and Injuries; Disease Attributes; Compulsive Behavior; Impulsive Behavior; Alcoholism; Recurrence; Behavior, Addictive; Fractures, Stress
• Other Study ID Numbers: TRR265 A03

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No