Alcohol Use DisorderNCT04128228

Neurobiological Responses in Alcoholism and Early Trauma

A study testing 8-week outpatient treatment in people with Alcohol Use Disorder and Early Trauma Complications, run by Yale University at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 21 to 55 yearsHealthy volunteers can take part
Conditions the study is for: Alcohol Use Disorder, Early Trauma Complications
What is being tested?: 8-week outpatient treatment
Type of treatment: Lifestyle or therapy programme
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 148 participants
Where: 1 siteUnited States
Study dates: 3 Oct 2019to 8 Sep 2023
Phase: Interventional
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 21 to 55 years
All sexes
Healthy volunteers accepted
Adult

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 exclusion criteria (e.g., claustrophobia, implanted metal in the body)

Trial locations and contacts

1 site in 1 country.

United States1 site

Yale University
New Haven, Connecticut, 06492

Other trials in United States

About this study

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.

Read the 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.

Conditions: Alcohol Use Disorder, Early Trauma Complications
Being tested: 8-week outpatient treatment
Keywords: Alcohol use disorder, Early trauma, fMRI, Stress hormone, Alcohol relapse
Medical subject headings: Alcoholism, Wounds and Injuries

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

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

Study groups in NCT04128228
Study group	Role	What they receive
Alcohol use disorder with early trauma	Other	Individuals with alcohol use disorder participated in an equivalent 8-week outpatient treatment program. Receives: Behavioral: 8-week outpatient treatment
Alcohol use disorder without early trauma	Other	Individuals with alcohol use disorder participated in an equivalent 8-week outpatient treatment program. Receives: Behavioral: 8-week outpatient treatment
Controls with early trauma	No intervention	Control participants did not receive any treatment.
Controls without early trauma	No intervention	Control participants did not receive any treatment.

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: baseline
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.
Measured: baseline
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.
Measured: up to 90 days

Secondary outcomes (2)

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.
Measured: up to 90 days
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.
Measured: up to 90 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

3 Oct 20198 Sep 2023

First posted16 Oct 2019
Study start3 Oct 2019
Primary completion8 Sep 2023
Study completion8 Sep 2023

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Alcohol Use DisorderStudies of the same condition, open and under way.
More trials run by Yale UniversityThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase N/A
Primary purpose: Basic science
Allocation: Non-randomised
Intervention model: Parallel groups
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.
Masking: None (open label)
Enrolment: 148 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04128228
Sponsor's protocol ID: 2000024809
Other IDs: 1R01AA026844
Status last verified: Oct 2024
First submitted: 14 Oct 2019
Last updated: 14 Nov 2024
Results posted: Yes, on ClinicalTrials.gov
FDA-regulated drug: No
FDA-regulated device: No

Publications

Seo D, Choi JJ, Goldberg LM, Sinha R. Integrating breathing-based stress reduction to address stress and alcohol misuse: A novel digital intervention delivered via telehealth and smartphone application. Alcohol Clin Exp Res (Hoboken). 2025 Sep;49(9):2076-2091. doi: 10.1111/acer.70131. Epub 2025 Aug 9.
PubMed 40781881

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 14 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Neurobiological Responses in Alcoholism and Early Trauma
ClinicalTrials.gov ID: NCT04128228
Acronym / sponsor ID: 2000024809
Conditions: Alcohol Use Disorder, Early Trauma Complications
Keywords: Alcohol use disorder, Early trauma, fMRI, Stress hormone, Alcohol relapse
Study type: Interventional
Recruitment status: Completed
Enrolment: 148 participants (actual)
Lead sponsor: Yale UniversityUniversity, hospital or other
Collaborators: National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Study start: 3 Oct 2019 (actual)
Primary completion: 8 Sep 2023 (actual)
Study completion: 8 Sep 2023 (actual)
First posted: 16 Oct 2019 (actual)
Results: Posted 14 Nov 2024

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Basic science
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 4
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.

Arm	Type	Receives
Alcohol use disorder with early trauma	Other	Behavioral: 8-week outpatient treatmentIndividuals with alcohol use disorder participated in an equivalent 8-week outpatient treatment program.
Alcohol use disorder without early trauma	Other	Behavioral: 8-week outpatient treatmentIndividuals with alcohol use disorder participated in an equivalent 8-week outpatient treatment program.
Controls with early trauma	No intervention	–Control participants did not receive any treatment.
Controls without early trauma	No intervention	–Control participants did not receive any treatment.

Who may qualify

Ages: 21 to 55 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
8-week outpatient treatmentIndividuals with AUD participated in an 8-week treatment program integrating cognitive behavioral techniques focused on emotion regulation with breathing-based stress management.	Behavioural	Alcohol use disorder with early trauma, Alcohol use disorder without early trauma

Primary outcome

Brain Response
Time frame: baseline
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.
Stress Hormone Response (Cortisol to ACTH Ratio)
Time frame: baseline
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 to Relapse
Time frame: up to 90 days
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.

2 secondary outcomes

Amount of Alcohol Consumption (Weekly)
Time frame: up to 90 days
Frequency of Alcohol Use (Percentage)
Time frame: up to 90 days

Results and safety

Results posted to the registry on 14 Nov 2024, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
AUD/ET	34	29
AUD/NT	33	28
MD/ET	27	27
MD/NT	37	37

Primary outcome: Brain Response

Time frame: baseline. Mean (Standard Deviation). Unit: unitless

Measure	AUD/ET n = 33	AUD/NT n = 31	MD/ET n = 27	MD/NT n = 37
R. VmPFC response to stress cue	.015 (.31)	.010 (.19)	-.013 (.19)	.08 (.19)
R. VmPFC response to alcohol cue	.071 (.33)	.058 (.19)	-.042 (.28)	.067 (.022)
R. VmPFC response to neutral cue	.042 (.24)	.01 (.31)	-.091 (.30)	.017 (.22)

AUD/ET vs AUD/NT vs MD/ET vs MD/NT: F value for the 2 X 2 Group Interaction: 5.5, p <0.05, Linear Mixed Model

Population analysed: 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.

Primary outcome: Stress Hormone Response (Cortisol to ACTH Ratio)

Time frame: baseline. Mean (Standard Deviation). Unit: µg/dL per pg/ml

Measure	AUD/ET n = 29	AUD/NT n = 29	MD/ET n = 22	MD/NT n = 31
Value	.14 (.09)	.11 (.05)	.19 (.09)	.17 (.11)

AUD/ET vs AUD/NT vs MD/ET vs MD/NT: F value: 4.79, p <0.01, ANOVA

Population analysed: 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).

Primary outcome: Time to Relapse

Time frame: up to 90 days. Mean (Standard Deviation). Unit: days to first drink after treatment

Measure	AUD/ET n = 29	AUD/NT n = 26
Value	22.8 (34.0)	5.6 (8.7)

AUD/ET vs AUD/NT: Hazard Ratio (HR): .71 (95% CI .53 to .95), p <0.05, Regression, Cox

Population analysed: 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.

2 secondary outcomes are reported in the full results.

Adverse events

Time frame: 5.5 months for individuals with alcohol use disorder; 1.5 months for individuals without alcohol use disorder. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
AUD/ET	0 of 34 (0%)	4 of 34 (11.8%)	0 of 34
AUD/NT	0 of 33 (0%)	0 of 33 (0%)	0 of 33
MD/ET	0 of 27 (0%)	0 of 27 (0%)	0 of 27
MD/NT	0 of 37 (0%)	0 of 37 (0%)	0 of 37

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 14 Nov 2024.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 40781881Seo D, Choi JJ, Goldberg LM, Sinha R. Integrating breathing-based stress reduction to address stress and alcohol misuse: A novel digital intervention delivered via telehealth and smartphone application. Alcohol Clin Exp Res (Hoboken). 2025 Sep;49(9):2076-2091. doi: 10.1111/acer.70131. Epub 2025 Aug 9.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Dongju Seo, PhD principal investigator

Yale University

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A study testing 8-week outpatient treatment in people with Alcohol Use Disorder and Early Trauma Complications, run by Yale University at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 14 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Yes. Results are posted in the registry (first posted 14 Nov 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Brain Response (time frame: baseline). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04128228, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Nov 2024.