Anxiety During Abstinence in AUD

Early Phase 1

Not yet recruiting

• Conditions: Alcohol Use Disorder
• Interventions: Drug: Disulfiram 250 mg; Diagnostic Test: functional MRI

• Registration Number: NCT06793488
• Lead Sponsor: Columbia University

Brief Summary

The goal of this study is to better understand the underlying neurobiological basis of anxiety that emerges during abstinence in patients with alcohol use disorder (AUD). The main questions it aims to answer are:

1. To characterize anxiety itself as well as anxiety related-neurobiological circuitry in early abstinence in AUD

2. To examine how anxiety and anxiety related-neurobiological circuitry change over the course of abstinence in AUD

Researchers will recruit both participants with AUD and healthy volunteers.

The participants with AUD will be prescribed disulfiram, a medication that helps participants with AUD stay abstinent. Healthy volunteers will not receive antabuse. Patients with AUD will undergo fMRI scanning both after 1 week and 3 months of disulfiram treatment. Healthy volunteers will undergo fMRI once.

Detailed Description

This study will recruit 40 treatment-seeking participants with AUD ("AUDP") and 20 age matched healthy volunteer participants (HVP). AUDP will be initiated on disulfiram, a medication FDA approved for alcohol use disorder that is a first line treatment for maintenance of abstinence from alcohol, to facilitate and help ensure abstinence from alcohol and will undergo functional MRI scanning at two timepoints: 1) 8-14 days after the last drink ("early abstinence") and 2) after three months of abstinence ("protracted abstinence"). HVP will be scanned once. The investigators will examine the functioning of the Anterior Insula (AI), Bed Nucleus of the Stria Terminalis (BNST), and Dorsolateral Prefrontal Cortex (DLPFC) during a task that evokes anxiety while anticipating an uncertain threat ("threat-anxiety") as well as resting state functional connectivity (RSFC) between AI-BNST and AI-DLPFC to measure whether there are neuroplastic changes in these circuits that occur during abstinence. These changes in anxiety circuit activity and connectivity will be related to changes in current anxiety symptoms.

Study Timeline

• Study First Submitted: 2025-01-21
• Study First Submitted QC: 2025-01-21
• Study First Posted: 2025-01-27
• Status Verified: 2025-06
• Last Update Submitted: 2025-06-10
• Last Update Posted: 2025-06-11
• Study Start: 2025-07-15
• Primary Completion: 2029-08-30
• Study Completion: 2029-08-30

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 60

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Participants with Alcohol Use Disorder	Disulfiram 250 mg	Participants with Alcohol Use Disorder (AUDP) will be participants (n=40) ages 21-39 with alcohol use disorder (AUD) who are seeking treatment for AUD. They will undergo 3 months of treatment with disulfiram 250mg daily with supervised dosing and undergo fMRI scanning after 1 week and 3 months of disulfiram treatment.
Participants with Alcohol Use Disorder	functional MRI	Participants with Alcohol Use Disorder (AUDP) will be participants (n=40) ages 21-39 with alcohol use disorder (AUD) who are seeking treatment for AUD. They will undergo 3 months of treatment with disulfiram 250mg daily with supervised dosing and undergo fMRI scanning after 1 week and 3 months of disulfiram treatment.
Healthy volunteer participants	functional MRI	Healthy volunteer participants will be participants (n=20) ages 21-39 without a history of alcohol or other substance use disorders. They will undergo fMRI scanning once.

Primary Outcome Measures

Name	Time	Method
AI-BNST Resting state functional connectivity correlation (R) value	1 week and 3 months	Resting state functional connectivity between the bed nucleus of the stria terminalis and anterior insula resting state functional connectivity. Correlation values range from -1 to +1, with higher values indicating stronger connectivity.
AI-BNST task activation t statistic	1 week and 3 months	Unpredictable threat task activation of the bed nucleus of the stria terminalis and anterior insula. T statistics range from negative infinity to positive infinity. The farther the t statistic is away from zero (positively), this indicates a larger magnitude in brain activation
State trait anxiety inventory score	1 week and 3 months	The State-Trait Anxiety Inventory (STAI) score ranges from 20-80, with higher scores indicating greater anxiety

Trial Locations

Locations (1)

Columbia University Irving Medical Center; 🇺🇸 New York, New York, United States