Trial Outcomes & Findings for Neurobiological Responses in Alcoholism and Early Trauma (NCT NCT04128228)
NCT ID: NCT04128228
Last Updated: 2024-11-14
Results Overview
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.
COMPLETED
NA
148 participants
baseline
2024-11-14
Participant Flow
All participants were recruited starting on October 3, 2019 through online platforms and flyers. A recruitment center was located in New Haven, Connecticut.
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).
Participant milestones
| Measure |
AUD/ET
Individuals with alcohol use disorder and early trauma:
Individuals with alcohol use disorder will receive an 8-week outpatient treatment, involving two sessions per week that integrate cognitive behavioral therapy with breathing-based stress management.
|
AUD/NT
Individuals with alcohol use disorder without early trauma:
Individuals with alcohol use disorder will receive an 8-week outpatient treatment, involving two sessions per week that integrate cognitive behavioral therapy with breathing-based stress management.
|
MD/ET
Moderate social drinkers (controls) with a history of early trauma: Control participants will undergo a baseline assessment without receiving any outpatient treatment.
|
MD/NT
Moderate social drinkers (controls) without a history of early trauma: Control participants will undergo a baseline assessment without receiving any outpatient treatment.
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
34
|
33
|
27
|
37
|
|
Overall Study
COMPLETED
|
29
|
28
|
27
|
37
|
|
Overall Study
NOT COMPLETED
|
5
|
5
|
0
|
0
|
Reasons for withdrawal
| Measure |
AUD/ET
Individuals with alcohol use disorder and early trauma:
Individuals with alcohol use disorder will receive an 8-week outpatient treatment, involving two sessions per week that integrate cognitive behavioral therapy with breathing-based stress management.
|
AUD/NT
Individuals with alcohol use disorder without early trauma:
Individuals with alcohol use disorder will receive an 8-week outpatient treatment, involving two sessions per week that integrate cognitive behavioral therapy with breathing-based stress management.
|
MD/ET
Moderate social drinkers (controls) with a history of early trauma: Control participants will undergo a baseline assessment without receiving any outpatient treatment.
|
MD/NT
Moderate social drinkers (controls) without a history of early trauma: Control participants will undergo a baseline assessment without receiving any outpatient treatment.
|
|---|---|---|---|---|
|
Overall Study
Withdrawal by Subject
|
3
|
3
|
0
|
0
|
|
Overall Study
noncompliance
|
2
|
2
|
0
|
0
|
Baseline Characteristics
Neurobiological Responses in Alcoholism and Early Trauma
Baseline characteristics by cohort
| Measure |
AUD/ET
n=34 Participants
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.
|
AUD/NT
n=33 Participants
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.
|
MD/ET
n=27 Participants
Moderate drinkers (controls) with early trauma:
Control participants completed baseline assessments without receiving any outpatient treatment.
|
MD/NT
n=37 Participants
Moderate drinkers (controls) without early trauma:
Control participants completed baseline assessments without receiving any outpatient treatment.
|
Total
n=131 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
34.1 years
STANDARD_DEVIATION 9.0 • n=5 Participants
|
35.94 years
STANDARD_DEVIATION 9.1 • n=7 Participants
|
31.6 years
STANDARD_DEVIATION 7.5 • n=5 Participants
|
32.0 years
STANDARD_DEVIATION 7.7 • n=4 Participants
|
33.5 years
STANDARD_DEVIATION 8.4 • n=21 Participants
|
|
Sex: Female, Male
Female
|
19 Participants
n=5 Participants
|
13 Participants
n=7 Participants
|
16 Participants
n=5 Participants
|
16 Participants
n=4 Participants
|
64 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
15 Participants
n=5 Participants
|
20 Participants
n=7 Participants
|
11 Participants
n=5 Participants
|
21 Participants
n=4 Participants
|
67 Participants
n=21 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
6 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
12 Participants
n=4 Participants
|
32 Participants
n=21 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
28 Participants
n=5 Participants
|
26 Participants
n=7 Participants
|
20 Participants
n=5 Participants
|
25 Participants
n=4 Participants
|
99 Participants
n=21 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
2 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Asian
|
3 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
12 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Black or African American
|
10 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
8 Participants
n=4 Participants
|
30 Participants
n=21 Participants
|
|
Race (NIH/OMB)
White
|
17 Participants
n=5 Participants
|
24 Participants
n=7 Participants
|
10 Participants
n=5 Participants
|
21 Participants
n=4 Participants
|
72 Participants
n=21 Participants
|
|
Race (NIH/OMB)
More than one race
|
3 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
6 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
5 Participants
n=4 Participants
|
9 Participants
n=21 Participants
|
|
Region of Enrollment
United States
|
34 participants
n=5 Participants
|
33 participants
n=7 Participants
|
27 participants
n=5 Participants
|
37 participants
n=4 Participants
|
131 participants
n=21 Participants
|
|
Early Trauma Score
|
60.2 units on a scale
STANDARD_DEVIATION 17.3 • n=5 Participants
|
34.4 units on a scale
STANDARD_DEVIATION 6.2 • n=7 Participants
|
63.3 units on a scale
STANDARD_DEVIATION 13.6 • n=5 Participants
|
30.6 units on a scale
STANDARD_DEVIATION 5.8 • n=4 Participants
|
46.0 units on a scale
STANDARD_DEVIATION 18.7 • n=21 Participants
|
|
Amount of alcohol consumption (weekly)
|
18.9 alcohol drinks (weekly)
STANDARD_DEVIATION 15.8 • n=5 Participants
|
19.6 alcohol drinks (weekly)
STANDARD_DEVIATION 13.6 • n=7 Participants
|
1.9 alcohol drinks (weekly)
STANDARD_DEVIATION 2.1 • n=5 Participants
|
2.2 alcohol drinks (weekly)
STANDARD_DEVIATION 2.0 • n=4 Participants
|
10.8 alcohol drinks (weekly)
STANDARD_DEVIATION 13.6 • n=21 Participants
|
|
Days of alcohol consumption (weekly)
|
4.0 days of alcohol use (weekly)
STANDARD_DEVIATION 2.2 • n=5 Participants
|
4.1 days of alcohol use (weekly)
STANDARD_DEVIATION 2.0 • n=7 Participants
|
0.9 days of alcohol use (weekly)
STANDARD_DEVIATION 0.9 • n=5 Participants
|
1.2 days of alcohol use (weekly)
STANDARD_DEVIATION 1.0 • n=4 Participants
|
2.6 days of alcohol use (weekly)
STANDARD_DEVIATION 2.2 • n=21 Participants
|
PRIMARY outcome
Timeframe: baselinePopulation: 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.
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.
Outcome measures
| Measure |
AUD/ET
n=33 Participants
Individuals with alcohol use disorder and early trauma:
Individuals with alcohol use disorder completed baseline assessments, including multimodal neuroimaging, and then received an 8-week outpatient treatment that integrates alcohol treatment based on cognitive behavioral methods with breathing-based stress management.
|
AUD/NT
n=31 Participants
Individuals with alcohol use disorder without early trauma:
Individuals with alcohol use disorder completed baseline assessments, including multimodal neuroimaging, and then received an 8-week outpatient treatment that integrates alcohol treatment based on cognitive behavioral methods with breathing-based stress management.
|
MD/ET
n=27 Participants
Moderate drinkers (controls) with early trauma:
Control participants completed baseline assessments, including multimodal neuroimaging, without receiving any outpatient treatment.
|
MD/NT
n=37 Participants
Moderate drinkers (controls) without early trauma:
Control participants completed baseline assessments, including multimodal neuroimaging, without receiving any outpatient treatment.
|
|---|---|---|---|---|
|
Brain Response
R. VmPFC response to stress cue
|
.015 unitless
Standard Deviation .31
|
.010 unitless
Standard Deviation .19
|
-.013 unitless
Standard Deviation .19
|
.08 unitless
Standard Deviation .19
|
|
Brain Response
R. VmPFC response to alcohol cue
|
.071 unitless
Standard Deviation .33
|
.058 unitless
Standard Deviation .19
|
-.042 unitless
Standard Deviation .28
|
.067 unitless
Standard Deviation .022
|
|
Brain Response
R. VmPFC response to neutral cue
|
.042 unitless
Standard Deviation .24
|
.01 unitless
Standard Deviation .31
|
-.091 unitless
Standard Deviation .30
|
.017 unitless
Standard Deviation .22
|
PRIMARY outcome
Timeframe: baselinePopulation: 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).
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.
Outcome measures
| Measure |
AUD/ET
n=29 Participants
Individuals with alcohol use disorder and early trauma:
Individuals with alcohol use disorder completed baseline assessments, including multimodal neuroimaging, and then received an 8-week outpatient treatment that integrates alcohol treatment based on cognitive behavioral methods with breathing-based stress management.
|
AUD/NT
n=29 Participants
Individuals with alcohol use disorder without early trauma:
Individuals with alcohol use disorder completed baseline assessments, including multimodal neuroimaging, and then received an 8-week outpatient treatment that integrates alcohol treatment based on cognitive behavioral methods with breathing-based stress management.
|
MD/ET
n=22 Participants
Moderate drinkers (controls) with early trauma:
Control participants completed baseline assessments, including multimodal neuroimaging, without receiving any outpatient treatment.
|
MD/NT
n=31 Participants
Moderate drinkers (controls) without early trauma:
Control participants completed baseline assessments, including multimodal neuroimaging, without receiving any outpatient treatment.
|
|---|---|---|---|---|
|
Stress Hormone Response (Cortisol to ACTH Ratio)
|
.14 µg/dL per pg/ml
Standard Deviation .09
|
.11 µg/dL per pg/ml
Standard Deviation .05
|
.19 µg/dL per pg/ml
Standard Deviation .09
|
.17 µg/dL per pg/ml
Standard Deviation .11
|
PRIMARY outcome
Timeframe: up to 90 daysPopulation: 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.
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.
Outcome measures
| Measure |
AUD/ET
n=29 Participants
Individuals with alcohol use disorder and early trauma:
Individuals with alcohol use disorder completed baseline assessments, including multimodal neuroimaging, and then received an 8-week outpatient treatment that integrates alcohol treatment based on cognitive behavioral methods with breathing-based stress management.
|
AUD/NT
n=26 Participants
Individuals with alcohol use disorder without early trauma:
Individuals with alcohol use disorder completed baseline assessments, including multimodal neuroimaging, and then received an 8-week outpatient treatment that integrates alcohol treatment based on cognitive behavioral methods with breathing-based stress management.
|
MD/ET
Moderate drinkers (controls) with early trauma:
Control participants completed baseline assessments, including multimodal neuroimaging, without receiving any outpatient treatment.
|
MD/NT
Moderate drinkers (controls) without early trauma:
Control participants completed baseline assessments, including multimodal neuroimaging, without receiving any outpatient treatment.
|
|---|---|---|---|---|
|
Time to Relapse
|
22.8 days to first drink after treatment
Standard Deviation 34.0
|
5.6 days to first drink after treatment
Standard Deviation 8.7
|
—
|
—
|
SECONDARY outcome
Timeframe: up to 90 daysPopulation: 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.
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.
Outcome measures
| Measure |
AUD/ET
n=29 Participants
Individuals with alcohol use disorder and early trauma:
Individuals with alcohol use disorder completed baseline assessments, including multimodal neuroimaging, and then received an 8-week outpatient treatment that integrates alcohol treatment based on cognitive behavioral methods with breathing-based stress management.
|
AUD/NT
n=25 Participants
Individuals with alcohol use disorder without early trauma:
Individuals with alcohol use disorder completed baseline assessments, including multimodal neuroimaging, and then received an 8-week outpatient treatment that integrates alcohol treatment based on cognitive behavioral methods with breathing-based stress management.
|
MD/ET
Moderate drinkers (controls) with early trauma:
Control participants completed baseline assessments, including multimodal neuroimaging, without receiving any outpatient treatment.
|
MD/NT
Moderate drinkers (controls) without early trauma:
Control participants completed baseline assessments, including multimodal neuroimaging, without receiving any outpatient treatment.
|
|---|---|---|---|---|
|
Amount of Alcohol Consumption (Weekly)
|
5.6 alcohol drinks (weekly)
Standard Deviation 8.1
|
13.1 alcohol drinks (weekly)
Standard Deviation 8.4
|
—
|
—
|
SECONDARY outcome
Timeframe: up to 90 daysPopulation: 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.
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.
Outcome measures
| Measure |
AUD/ET
n=29 Participants
Individuals with alcohol use disorder and early trauma:
Individuals with alcohol use disorder completed baseline assessments, including multimodal neuroimaging, and then received an 8-week outpatient treatment that integrates alcohol treatment based on cognitive behavioral methods with breathing-based stress management.
|
AUD/NT
n=25 Participants
Individuals with alcohol use disorder without early trauma:
Individuals with alcohol use disorder completed baseline assessments, including multimodal neuroimaging, and then received an 8-week outpatient treatment that integrates alcohol treatment based on cognitive behavioral methods with breathing-based stress management.
|
MD/ET
Moderate drinkers (controls) with early trauma:
Control participants completed baseline assessments, including multimodal neuroimaging, without receiving any outpatient treatment.
|
MD/NT
Moderate drinkers (controls) without early trauma:
Control participants completed baseline assessments, including multimodal neuroimaging, without receiving any outpatient treatment.
|
|---|---|---|---|---|
|
Frequency of Alcohol Use (Percentage)
|
26.1 Percentage of alcohol use days
Standard Deviation 29.4
|
45.4 Percentage of alcohol use days
Standard Deviation 25.0
|
—
|
—
|
Adverse Events
AUD/ET
AUD/NT
MD/ET
MD/NT
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
AUD/ET
n=34 participants at risk
Individuals with alcohol use disorder and early trauma:
Individuals with alcohol use disorder completed baseline assessments including multimodal neuroimaging. Then, they participated in an 8-week outpatient treatment program integrating cognitive-behavioral techniques focused on emotion regulation with breathing-based stress management.
|
AUD/NT
n=33 participants at risk
Individuals with alcohol use disorder without early trauma:
Individuals with alcohol use disorder completed baseline assessments including multimodal neuroimaging. Then, they participated in an 8-week outpatient treatment program integrating cognitive-behavioral techniques focused on emotion regulation with breathing-based stress management.
|
MD/ET
n=27 participants at risk
Moderate drinkers (controls) with early trauma:
Control participants completed baseline assessments including multimodal neuroimaging but did not receive any treatment.
|
MD/NT
n=37 participants at risk
Moderate drinkers (controls) without early trauma:
Control participants completed baseline assessments including multimodal neuroimaging but did not receive any treatment.
|
|---|---|---|---|---|
|
Musculoskeletal and connective tissue disorders
low back pain
|
5.9%
2/34 • Number of events 3 • 5.5 months for individuals with alcohol use disorder; 1.5 months for individuals without alcohol use disorder
|
0.00%
0/33 • 5.5 months for individuals with alcohol use disorder; 1.5 months for individuals without alcohol use disorder
|
0.00%
0/27 • 5.5 months for individuals with alcohol use disorder; 1.5 months for individuals without alcohol use disorder
|
0.00%
0/37 • 5.5 months for individuals with alcohol use disorder; 1.5 months for individuals without alcohol use disorder
|
|
Respiratory, thoracic and mediastinal disorders
COVID-19
|
5.9%
2/34 • Number of events 2 • 5.5 months for individuals with alcohol use disorder; 1.5 months for individuals without alcohol use disorder
|
0.00%
0/33 • 5.5 months for individuals with alcohol use disorder; 1.5 months for individuals without alcohol use disorder
|
0.00%
0/27 • 5.5 months for individuals with alcohol use disorder; 1.5 months for individuals without alcohol use disorder
|
0.00%
0/37 • 5.5 months for individuals with alcohol use disorder; 1.5 months for individuals without alcohol use disorder
|
Additional Information
Dongju Seo
Department of Psychiatry, Yale University School of Medicine
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place