Adverse Childhood Experiences in Alcohol Use Disorder

• ClinicalTrials.gov Identifier: NCT05048758
• Recruitment Status: Completed
• First Posted: September 17, 2021
• Last Update Posted: March 29, 2024
• Sponsor: Central Institute of Mental Health, Mannheim
• Collaborator: German Research Foundation
• Information provided by (Responsible Party): Central Institute of Mental Health, Mannheim

Tracking Information

• First Submitted Date: September 8, 2021
• First Posted Date: September 17, 2021
• Last Update Posted Date: March 29, 2024
• Actual Study Start Date: November 22, 2021
• Actual Primary Completion Date: January 17, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 8, 2021)

• fMRI to assess group and within-subjects differences in task-specific brain activation patterns: Stress-sensitivity [ Time Frame: fMRI measurement at one day only (day of fMRI experiment) ]
  Stress-sensitivity: Imaging Stress Task to assess neural activation patterns during mental arithmetic tasks with negative feedback
• fMRI to assess group and within-subjects differences in task-specific brain activation patterns: Emotion processing [ Time Frame: fMRI measurement at one day only (day of fMRI experiment) ]
  Emotion-processing: emotional face-/form-matching task to assess neural activation patters of emotion processing
• fMRI to assess group and within-subjects differences in task-specific brain activation patterns: Alcohol cue-reactivity [ Time Frame: fMRI measurement at one day only (day of fMRI experiment) ]
  Alcohol cue-reactivity: pictures of alcoholic beverages to assess neural alcohol-cue reactivity
• fMRI to assess group differences in task-specific brain activation patterns: Response inhibition [ Time Frame: fMRI measurement at one day only (day of fMRI experiment) ]
  Response inhibition: Stop Signal Task (variation of go/no-go) to assess response inhibition.
• fMRI to assess group differences in task-specific brain activation patterns: Working memory [ Time Frame: fMRI measurement at one day only (day of fMRI experiment) ]
  Working memory: n-back task (continuous performance) to assess working memory function.
• Long-term alcohol consumption [ Time Frame: 2 - 2.5 year follow-up after first project ]
  Self-report in longitudinal sample measured with the LDH interview
• Short-term alcohol consumption [ Time Frame: 3-month follow-up after current project ]
  Self-report in whole sample measured with the Form 90 interview

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: September 8, 2021)

• Hormonal stress response using salivary cortisol level [ Time Frame: Normal awakening response on a subject's regular week-day (0, 0.5, 8 and 14 hours after wake-up) ]
  Collection of saliva on a subject's regular week-day for the individual's normal cortisol awakening response and circadian rhythm (basal hypothalamic-pituitary-adrenal-function at 0, 0.5, 8 and 14 hours after wake-up). Cortisol awakening reaction, area under the curve and slope will therefore be calculated [nmol/L]
• Hormonal stress response using salivary cortisol level [ Time Frame: day of fMRI experiment, at -45, -22, -10 minutes before and 35, 45, 60, 75 and 90 minutes after onset of stress induction ]
  Time course of salivary cortisol level. Area under the curve and slope will be calculated [nmol/L]
• GWAS and especially glutamatergic, serotonergic single-nucleotide polymorphisms [ Time Frame: Blood sample at one day only (day of fMRI experiment) ]
  Genomic DNA using 40ml EDTA-blood

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Adverse Childhood Experiences in Alcohol Use Disorder
• Official Title: Vulnerability for Alcohol Use Disorder After ACE: the Role of Stress Sensitivity, Emotion Processing, Cue Reactivity and Cognitive Functions in Relapse Risk
• Brief Summary: Adverse childhood experiences (ACE) and their relation to the development of an alcohol use disorder (AUD) will be measured with functional magnetic resonance imaging (fMRI).

Detailed Description

The aim of this study is to examine the impact of ACE on stress sensitivity, cue-reactivity, and emotion processing in individuals with AUD at a longitudinal level. For this, participants (excluding healthy controls) from the first project (see https://clinicaltrials.gov/ct2/show/NCT03758053) will be re-examined after 2 to 2.5 years to explore the involvement of these mechanisms in relation to (long-term) relapse risk, which is a central issue in substance use disorders. Furthermore, we will investigate cognitive functions, specifically response inhibition and working memory, in the relationship between ACE and AUD. Additional participants may be recruited to mitigate sample attrition from the first project and to achieve the desired sample size. To assess cognitive functions and data from new participants in relation to relapse risk, we will perform a 3-month follow-up.

Neural correlates of stress-sensitivity, emotion processing, alcohol cue-reactivity and cognitive functions will be assessed using fMRI. Furthermore, blood and saliva samples will be used to assess biological and physiological mechanisms (e.g. salivary cortisol level or genetic markers of AUD and possible gene-environment-interactions).

The current project is interested in the extent to which ACE severity modulates neural activation in specific brain regions during the execution of fMRI paradigms as well as alcohol-related measures (e.g., craving and alcohol consumption). Of particular interest is the question whether these neural and alcohol-related measures are associated with relapse risk.

55 individuals with AUD and varying levels of ACE will be examined using interviews, questionnaires, fMRI tasks as well as saliva and blood samples. Update from 29/03/2023: the relationships of interest will be examined using a dimensional approach to the predictor variable (ACE). Thus, participants will not be divided into two groups (no or mild ACE vs. moderate to severe ACE) as originally planned, but will instead be treated as one group with varying levels of ACE. The new sample size (n = 55) is based on an updated sample size calculation for a linear regression (two-tailed) using the following input parameters: f² = 0.15 (moderate effect size), alpha error = 0.05, and power = 80%. All ethical votes and informed consents of participants will be obtained according to the declaration of Helsinki.

• Study Type: Observational
• Study Design: Observational Model: Other; Time Perspective: Prospective
• Target Follow-Up Duration: Not Provided

Biospecimen

Retention:   Samples With DNA

Description:

Saliva (stress hormones) Blood (genotyping)

• Sampling Method: Non-Probability Sample
• Study Population: Patients from the Addiction Clinic at the Central Institute of Mental Health (Mannheim, Germany), as well as residents predominantly from the Mannheim/Heidelberg area who answered an open call to participate in this study.

Condition

• Alcohol Use Disorder
• Trauma, Psychological

Intervention

Other: No intervention

No intervention

Other Name: Observational study

Study Groups/Cohorts

Individuals with AUD + varying levels of ACE

Individuals with alcohol use disorder (AUD) and varying levels of adverse childhood experiences (ACE)

Intervention: Other: No intervention

• Publications *: Turkmen C, Machunze N, Tan H, Gerhardt S, Kiefer F, Vollstadt-Klein S. Vulnerability for alcohol use disorder after adverse childhood experiences (AUDACE): protocol for a longitudinal fMRI study assessing neuropsychobiological risk factors for relapse. BMJ Open. 2022 Jun 30;12(6):e058645. doi: 10.1136/bmjopen-2021-058645.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: March 28, 2024): 43
• Original Estimated Enrollment (submitted: September 8, 2021): 60
• Actual Study Completion Date: January 17, 2024
• Actual Primary Completion Date: January 17, 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Male and female
• Age between 18 and 65
• Normal or correctable eyesight
• Sufficient ability to communicate with the investigators, to answer questions in oral and written form
• "Fully Informed Consent"
• "Written Informed Consent"
• Individuals with alcohol use disorder according to DSM-5 or 'heavy drinking' (alcohol intake > 40g/ more than 5 days (women) & 60g/ more than 5 days (men) and varying levels of adverse childhood experiences

Exclusion Criteria:

• Withdrawal of the declaration of consent
• Exclusion criteria for an MRI scan (pregnancy, metal implants, etc.)
• Severe internal, neurological and psychiatric comorbidities
• Pharmacotherapy with psychoactive substances within the last 14 days (except treatment with SSRI/SNRIs for at least 28 days)
• Axis-I disorder according to ICD-10 and DSM 5 (except tobacco and alcohol use disorder, substance abuse with less than 2(11) criteria according to DSM-5, mild depressive episode, adaptation disorder and specific phobia within the last 12 months)
• Positive urin drug screening (cannabis, amphetamine, opiates, benzodiazepines, cocaine)
• Withdrawal symptoms (CIWA-R > 7)
• Intoxication at time of investigation (breathalyzer > 0.3‰)
• Suicidal tendency or potential danger for others

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 65 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Germany

Administrative Information

• NCT Number: NCT05048758
• Other Study ID Numbers: GRK2350-B5-P2
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Central Institute of Mental Health, Mannheim
• Original Responsible Party: Same as current
• Current Study Sponsor: Central Institute of Mental Health, Mannheim
• Original Study Sponsor: Same as current
• Collaborators: German Research Foundation

Investigators

• Principal Investigator: Sabine Vollstaedt-Klein, PhD; Central Institute of Mental Health, Mannheim

• PRS Account: Central Institute of Mental Health, Mannheim
• Verification Date: March 2024