Skip to content

Neurobiological Responses in Alcoholism and Early Trauma

Neurobiological Responses in Alcoholism and Early Trauma

Status
Completed
Phases
NA
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT04128228
Enrollment
148
Registered
2019-10-16
Start date
2019-10-03
Completion date
2023-09-08
Last updated
2024-11-14

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Alcohol Use Disorder, Early Trauma Complications

Keywords

Alcohol use disorder, Early trauma, fMRI, Stress hormone, Alcohol relapse

Brief summary

Alcohol use disorder (AUD) accompanied by early trauma presents clinical challenges, including elevated rates of comorbid emotional symptoms and relapse. To better understand this co-occurring condition, this study investigates the neurobiological responses associated with AUD and early trauma. Using a multimodal neuroimaging approach, including functional magnetic resonance imaging (fMRI), the study concurrently measures brain activity and stress hormone responses in individuals with AUD and control participants, both with and without early trauma. The primary goal is to examine neurobiological responses and relapse patterns following treatment in individuals with AUD, with and without a history of early trauma. Conventional alcohol treatments often fail to specifically address the emotional complications in AUD individuals with early trauma. Therefore, this study also explores whether incorporating stress regulation into alcohol relapse prevention can improve outcomes for this population. Following baseline assessments that included multimodal neuroimaging, all participants with AUD received an 8-week outpatient treatment program integrating cognitive-behavioral methods focused on emotion regulation with stress reduction techniques, particularly self-regulated breathing strategies.

Detailed description

The study recruited four demographically matched groups (age, sex ratio): individuals with AUD with and without a history of early trauma, and moderate drinkers with and without early trauma. Study procedures involved functional magnetic resonance imaging (fMRI), an eight-week outpatient treatment program, and a 90-day follow-up period. During fMRI sessions, participants engaged in a validated emotion provocation task, viewing stress, alcohol-cue, and neutral images while concurrent brain and stress hormone data are collected. Individuals with AUD completed baseline assessments, including multimodal neuroimaging, and then participated in an 8-week treatment program consisting of two sessions per week. This program integrated cognitive-behavioral techniques focused on emotion regulation with breathing-based stress management. Control participants completed baseline assessments including multimodal neuroimaging but did not receive any treatment. Following the treatment, participants with AUD were prospectively followed for 90 days, with remote follow-up interviews conducted at 14, 30, 90 days via video communication.

Interventions

BEHAVIORAL8-week outpatient treatment

Individuals with AUD participated in an 8-week treatment program integrating cognitive behavioral techniques focused on emotion regulation with breathing-based stress management.

Sponsors

National Institute on Alcohol Abuse and Alcoholism (NIAAA)
CollaboratorNIH
Yale University
Lead SponsorOTHER

Study design

Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE

Intervention model description

Following baseline assessments including multimodal neuroimaging, AUD individuals with and without a history of early trauma received an equivalent 8-week outpatient treatment. Control participants with and without early trauma did not receive any treatment after baseline assessments.

Eligibility

Sex/Gender
ALL
Age
21 Years to 55 Years
Healthy volunteers
Yes

Inclusion criteria

AUD inclusion Criteria: * Alcohol use disorder * Either low or high early trauma (based on the Childhood Trauma Questionnaire) * Body mass index (BMI) up to 35 (due to weight limitations of the MRI scanner) AUD

Exclusion criteria

* Current or past substance use disorder other than alcohol; excluding caffeine and nicotine * Psychiatric disorders except for mood and anxiety disorders * Any significant current medical conditions * Women who are peri- and post- menopausal, pregnant or lactating * MRI specific

Design outcomes

Primary

MeasureTime frameDescription
Brain ResponsebaselineBrain responses during the viewing of stress, alcohol-cue, and neutral images were examined using functional magnetic resonance imaging (fMRI) during an emotion provocation task. A regions of interest (ROI) analysis was conducted to assess brain activity in the right ventromedial prefrontal cortex (VmPFC, BA10), a region identified a priori. The VmPFC ROI was defined using the Yale-Brodmann atlas, and beta values were obtained using the BioImage Suite. The beta coefficient represents the extent to which a specific condition contributes to changes in the BOLD (Blood Oxygen Level Dependent) signal in a particular brain region. A positive beta in the vmPFC would indicate an increased vmPFC response, whereas a negative beta would indicate a decreased vmPFC response compared to baseline. The magnitude of the beta reflects the strength of this effect: a larger absolute value, (whether positive or negative), suggests a greater change in brain activation in response to the condition.
Stress Hormone Response (Cortisol to ACTH Ratio)baselineCortisol to Adrenocorticotropic Hormone (ACTH) ratio indicates the relationship between cortisol secretion and ACTH stimulation at baseline. Cortisol is measured in micrograms per deciliter (µg/dL) and ACTH (adrenocorticotropic hormone) is measured in picograms per milliliter (pg/mL). Therefore, the unit of cortisol to ACTH ratio is expressed in µg/dL per pg/mL. Stress hormone samples were collected during the MRI scan.
Time to Relapseup to 90 daysThe first day of alcohol consumption after treatment during the 90-day follow-up period. Alcohol use data was measured using the Timeline Follow-Back (TLFB) method, a calendar-based self-report tool to track alcohol use. Participants recalled their drinking behavior using a calendar and reported both the days they consumed alcohol and the number of drinks consumed on each of those days. Alcohol use data during the 90-day follow-up period is available only for the AUD/ET and AUD/NT groups, as the MD/ET and MD/NT groups had not initiated treatment.

Secondary

MeasureTime frameDescription
Amount of Alcohol Consumption (Weekly)up to 90 daysAverage weekly alcohol consumption over the 90-day follow-up period. Alcohol use data was measured using the Timeline Follow-Back (TLFB) method, a calendar-based self-report tool to track alcohol use. Participants recalled their drinking behavior using a calendar and reported both the days they consumed alcohol and the number of drinks consumed on each of those days. Alcohol use data during the 90-day follow-up period is available only for the AUD/ET and AUD/NT groups, as the MD/ET and MD/NT groups had not initiated treatment.
Frequency of Alcohol Use (Percentage)up to 90 daysPercentage of alcohol use days over the 90-day follow-up period. Alcohol use data was measured using the Timeline Follow-Back (TLFB) method, a calendar-based self-report tool to track alcohol use. Participants recalled their drinking behavior using a calendar and reported both the days they consumed alcohol and the number of drinks consumed on each of those days. Alcohol use data during the 90-day follow-up period is available only for the AUD/ET and AUD/NT groups, as the MD/ET and MD/NT groups had not initiated treatment.

Countries

United States

Participant flow

Recruitment details

All participants were recruited starting on October 3, 2019 through online platforms and flyers. A recruitment center was located in New Haven, Connecticut.

Pre-assignment details

Out of the 148 enrolled participants, 17 individuals did not start the study due to participant withdrawal (N=14), MRI-day ineligibility (N=2), and non-compliance (N=1).

Participants by arm

ArmCount
AUD/ET
Individuals with alcohol use disorder (AUD) and early trauma (ET): Individuals with alcohol use disorder completed baseline assessments and then received an 8-week outpatient treatment that integrates alcohol treatment based on cognitive behavioral methods with breathing-based stress management.
34
AUD/NT
Individuals with alcohol use disorder without early trauma: Individuals with alcohol use disorder completed baseline assessments and then received an 8-week outpatient treatment that integrates alcohol treatment based on cognitive behavioral methods with breathing-based stress management.
33
MD/ET
Moderate drinkers (controls) with early trauma: Control participants completed baseline assessments without receiving any outpatient treatment.
27
MD/NT
Moderate drinkers (controls) without early trauma: Control participants completed baseline assessments without receiving any outpatient treatment.
37
Total131

Withdrawals & dropouts

PeriodReasonFG000FG001FG002FG003
Overall Studynoncompliance2200
Overall StudyWithdrawal by Subject3300

Baseline characteristics

CharacteristicAUD/ETTotalMD/NTMD/ETAUD/NT
Age, Continuous34.1 years
STANDARD_DEVIATION 9
33.5 years
STANDARD_DEVIATION 8.4
32.0 years
STANDARD_DEVIATION 7.7
31.6 years
STANDARD_DEVIATION 7.5
35.94 years
STANDARD_DEVIATION 9.1
Amount of alcohol consumption (weekly)18.9 alcohol drinks (weekly)
STANDARD_DEVIATION 15.8
10.8 alcohol drinks (weekly)
STANDARD_DEVIATION 13.6
2.2 alcohol drinks (weekly)
STANDARD_DEVIATION 2
1.9 alcohol drinks (weekly)
STANDARD_DEVIATION 2.1
19.6 alcohol drinks (weekly)
STANDARD_DEVIATION 13.6
Days of alcohol consumption (weekly)4.0 days of alcohol use (weekly)
STANDARD_DEVIATION 2.2
2.6 days of alcohol use (weekly)
STANDARD_DEVIATION 2.2
1.2 days of alcohol use (weekly)
STANDARD_DEVIATION 1
0.9 days of alcohol use (weekly)
STANDARD_DEVIATION 0.9
4.1 days of alcohol use (weekly)
STANDARD_DEVIATION 2
Early Trauma Score60.2 units on a scale
STANDARD_DEVIATION 17.3
46.0 units on a scale
STANDARD_DEVIATION 18.7
30.6 units on a scale
STANDARD_DEVIATION 5.8
63.3 units on a scale
STANDARD_DEVIATION 13.6
34.4 units on a scale
STANDARD_DEVIATION 6.2
Ethnicity (NIH/OMB)
Hispanic or Latino
6 Participants32 Participants12 Participants7 Participants7 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
28 Participants99 Participants25 Participants20 Participants26 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
0 Participants0 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants2 Participants0 Participants2 Participants0 Participants
Race (NIH/OMB)
Asian
3 Participants12 Participants3 Participants5 Participants1 Participants
Race (NIH/OMB)
Black or African American
10 Participants30 Participants8 Participants6 Participants6 Participants
Race (NIH/OMB)
More than one race
3 Participants6 Participants0 Participants2 Participants1 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants0 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
Unknown or Not Reported
1 Participants9 Participants5 Participants2 Participants1 Participants
Race (NIH/OMB)
White
17 Participants72 Participants21 Participants10 Participants24 Participants
Region of Enrollment
United States
34 participants131 participants37 participants27 participants33 participants
Sex: Female, Male
Female
19 Participants64 Participants16 Participants16 Participants13 Participants
Sex: Female, Male
Male
15 Participants67 Participants21 Participants11 Participants20 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
EG002
affected / at risk
EG003
affected / at risk
deaths
Total, all-cause mortality
0 / 340 / 330 / 270 / 37
other
Total, other adverse events
4 / 340 / 330 / 270 / 37
serious
Total, serious adverse events
0 / 340 / 330 / 270 / 37

Outcome results

Primary

Brain Response

Brain responses during the viewing of stress, alcohol-cue, and neutral images were examined using functional magnetic resonance imaging (fMRI) during an emotion provocation task. A regions of interest (ROI) analysis was conducted to assess brain activity in the right ventromedial prefrontal cortex (VmPFC, BA10), a region identified a priori. The VmPFC ROI was defined using the Yale-Brodmann atlas, and beta values were obtained using the BioImage Suite. The beta coefficient represents the extent to which a specific condition contributes to changes in the BOLD (Blood Oxygen Level Dependent) signal in a particular brain region. A positive beta in the vmPFC would indicate an increased vmPFC response, whereas a negative beta would indicate a decreased vmPFC response compared to baseline. The magnitude of the beta reflects the strength of this effect: a larger absolute value, (whether positive or negative), suggests a greater change in brain activation in response to the condition.

Time frame: baseline

Population: In AUD/ET, one participant did not complete the fMRI part of the study, resulting in N=33 for brain response. Among them, one participant only completed alcohol cue condition due to discomfort with the MRI scan. In AUD/NT, two participants did not complete the fMRI part of the study, resulting in N=31. In MD/ET, one participant did not complete the stress condition. In MD/NET, one participant did not complete the alcohol condition, and two participants did not complete the stress condition.

ArmMeasureGroupValue (MEAN)Dispersion
AUD/ETBrain ResponseR. VmPFC response to alcohol cue.071 unitlessStandard Deviation 0.33
AUD/ETBrain ResponseR. VmPFC response to stress cue.015 unitlessStandard Deviation 0.31
AUD/ETBrain ResponseR. VmPFC response to neutral cue.042 unitlessStandard Deviation 0.24
AUD/NTBrain ResponseR. VmPFC response to alcohol cue.058 unitlessStandard Deviation 0.19
AUD/NTBrain ResponseR. VmPFC response to neutral cue.01 unitlessStandard Deviation 0.31
AUD/NTBrain ResponseR. VmPFC response to stress cue.010 unitlessStandard Deviation 0.19
MD/ETBrain ResponseR. VmPFC response to stress cue-.013 unitlessStandard Deviation 0.19
MD/ETBrain ResponseR. VmPFC response to alcohol cue-.042 unitlessStandard Deviation 0.28
MD/ETBrain ResponseR. VmPFC response to neutral cue-.091 unitlessStandard Deviation 0.3
MD/NTBrain ResponseR. VmPFC response to alcohol cue.067 unitlessStandard Deviation 0.022
MD/NTBrain ResponseR. VmPFC response to neutral cue.017 unitlessStandard Deviation 0.22
MD/NTBrain ResponseR. VmPFC response to stress cue.08 unitlessStandard Deviation 0.19
Comparison: A regions of interest (ROI) analysis was conducted to evaluate brain activity in the right ventromedial prefrontal cortex (VmPFC, BA10), a region identified a priori. The VmPFC ROI was defined using the Yale-Brodmann atlas in the BioImage Suite application, from which the beta value for the VmPFC ROI was obtained for a Linear Mixed Model analysis.p-value: <0.05Linear Mixed Model
Primary

Stress Hormone Response (Cortisol to ACTH Ratio)

Cortisol to Adrenocorticotropic Hormone (ACTH) ratio indicates the relationship between cortisol secretion and ACTH stimulation at baseline. Cortisol is measured in micrograms per deciliter (µg/dL) and ACTH (adrenocorticotropic hormone) is measured in picograms per milliliter (pg/mL). Therefore, the unit of cortisol to ACTH ratio is expressed in µg/dL per pg/mL. Stress hormone samples were collected during the MRI scan.

Time frame: baseline

Population: Among the 33 AUD/ET participants who underwent MRI scans, 3 blood samples were not collected due to nurse unavailability (N=2) and difficult venous access (N=1). In the 31 AUD/NT MRI participants, two samples were not collected due to technical issues. Of the 27 MD/ET, 5 samples were not collected due to nurse unavailability (N=5) and a technical issue (N=1). Of the 37 MD/NT, 6 samples were not collected due to nurse unavailability (N=4), IV tubing issue (N=1), and participant refusal (N=1).

ArmMeasureValue (MEAN)Dispersion
AUD/ETStress Hormone Response (Cortisol to ACTH Ratio).14 µg/dL per pg/mlStandard Deviation 0.09
AUD/NTStress Hormone Response (Cortisol to ACTH Ratio).11 µg/dL per pg/mlStandard Deviation 0.05
MD/ETStress Hormone Response (Cortisol to ACTH Ratio).19 µg/dL per pg/mlStandard Deviation 0.09
MD/NTStress Hormone Response (Cortisol to ACTH Ratio).17 µg/dL per pg/mlStandard Deviation 0.11
p-value: <0.01ANOVA
Primary

Time to Relapse

The first day of alcohol consumption after treatment during the 90-day follow-up period. Alcohol use data was measured using the Timeline Follow-Back (TLFB) method, a calendar-based self-report tool to track alcohol use. Participants recalled their drinking behavior using a calendar and reported both the days they consumed alcohol and the number of drinks consumed on each of those days. Alcohol use data during the 90-day follow-up period is available only for the AUD/ET and AUD/NT groups, as the MD/ET and MD/NT groups had not initiated treatment.

Time frame: up to 90 days

Population: Among the 34 AUD/ET participants, one dropped out before starting treatment, leaving 33 to begin the 8-week intervention. Of these, 29 completed the treatment and follow-up. Among the 33 AUD/NT participants, two dropped out before the treatment, leaving 31 who initiated the treatment. Of these, 28 completed the treatment and two lost to follow-up for this measure. The MD/ET and MD/NT groups did not start treatment therefore no data was collected for the MD groups.

ArmMeasureValue (MEAN)Dispersion
AUD/ETTime to Relapse22.8 days to first drink after treatmentStandard Deviation 34
AUD/NTTime to Relapse5.6 days to first drink after treatmentStandard Deviation 8.7
p-value: <0.0595% CI: [0.53, 0.95]Regression, Cox
Secondary

Amount of Alcohol Consumption (Weekly)

Average weekly alcohol consumption over the 90-day follow-up period. Alcohol use data was measured using the Timeline Follow-Back (TLFB) method, a calendar-based self-report tool to track alcohol use. Participants recalled their drinking behavior using a calendar and reported both the days they consumed alcohol and the number of drinks consumed on each of those days. Alcohol use data during the 90-day follow-up period is available only for the AUD/ET and AUD/NT groups, as the MD/ET and MD/NT groups had not initiated treatment.

Time frame: up to 90 days

Population: Among the 34 AUD/ET participants, one dropped out before treatment, leaving 33 to start the intervention, with 29 completing treatment and follow-up (FU). Among the 33 AUD/NT participants, two dropped out before treatment, leaving 31 to initiate the intervention, with 28 completing treatment and three lost to follow-up for this measure (two before the 14-day FU, one before the 90-day FU). The MD/ET and MD/NT groups did not start treatment therefore no data was collected for the MD groups.

ArmMeasureValue (MEAN)Dispersion
AUD/ETAmount of Alcohol Consumption (Weekly)5.6 alcohol drinks (weekly)Standard Deviation 8.1
AUD/NTAmount of Alcohol Consumption (Weekly)13.1 alcohol drinks (weekly)Standard Deviation 8.4
p-value: <0.01t-test, 2 sided
Secondary

Frequency of Alcohol Use (Percentage)

Percentage of alcohol use days over the 90-day follow-up period. Alcohol use data was measured using the Timeline Follow-Back (TLFB) method, a calendar-based self-report tool to track alcohol use. Participants recalled their drinking behavior using a calendar and reported both the days they consumed alcohol and the number of drinks consumed on each of those days. Alcohol use data during the 90-day follow-up period is available only for the AUD/ET and AUD/NT groups, as the MD/ET and MD/NT groups had not initiated treatment.

Time frame: up to 90 days

Population: Among the 34 AUD/ET participants, one dropped out before treatment, leaving 33 to start the 8-week intervention, with 29 completing treatment and follow-up (FU). Among the 33 AUD/NT participants, two dropped out before treatment, leaving 31 to initiate the intervention, with 28 completing treatment and three lost to follow-up (two before the 14-day FU, one before the 90-day FU). The MD/ET and MD/NT groups did not start treatment therefore no data was collected for the MD groups.

ArmMeasureValue (MEAN)Dispersion
AUD/ETFrequency of Alcohol Use (Percentage)26.1 Percentage of alcohol use daysStandard Deviation 29.4
AUD/NTFrequency of Alcohol Use (Percentage)45.4 Percentage of alcohol use daysStandard Deviation 25
p-value: <0.05t-test, 2 sided

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026