Anxiety During Abstinence in AUD

NCT ID: NCT06793488

Last Updated: 2025-09-24

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-09-15
• Study Completion Date: 2029-08-30

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.

Conditions

Alcohol Use Disorder

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Participants with Alcohol Use Disorder

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.

Group Type: EXPERIMENTAL

Disulfiram 250 mg

Intervention Type: DRUG

Disulfiram will be used in Participants with Alcohol Use Disorder only to facilitate abstinence.

functional MRI

Intervention Type: DIAGNOSTIC_TEST

Participants will undergo fMRI scanning. Participants with alcohol use disorder will undergo scanning after 1 week and 3 months of disulfiram maintenance. Healthy volunteer participants will undergo scanning once.

Healthy volunteer participants

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.

Group Type: OTHER

functional MRI

Intervention Type: DIAGNOSTIC_TEST

Participants will undergo fMRI scanning. Participants with alcohol use disorder will undergo scanning after 1 week and 3 months of disulfiram maintenance. Healthy volunteer participants will undergo scanning once.

Interventions

Disulfiram 250 mg

Disulfiram will be used in Participants with Alcohol Use Disorder only to facilitate abstinence.

Intervention Type: DRUG

functional MRI

Participants will undergo fMRI scanning. Participants with alcohol use disorder will undergo scanning after 1 week and 3 months of disulfiram maintenance. Healthy volunteer participants will undergo scanning once.

Intervention Type: DIAGNOSTIC_TEST

Other Intervention Names

antabuse; fMRI

Eligibility Criteria

Inclusion Criteria

1. Between the ages of 21 and 40

2. Right-handed

3. Able to perform informed consent and comply with study

4. Seeking treatment for AUD

5. Meets The Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria for AUD of at least moderate severity (>3 symptoms)

1. Between the ages of 21 and 40

2. Right-handed

3. Able to perform informed consent and comply with study

4. Report drinking an average of fewer than 8/15 standard drinks per week for women/men and no more than 1 HDD (heavy drinking days) during the previous 28 days.

Exclusion Criteria

1. Neurological, medical or other conditions that would interfere with MRI scanning (e.g., history of stroke, seizure, brain tumor, brain infection, traumatic brain injury, multiple sclerosis, dementia, non MRI-compliant metal device in body, pregnancy, claustrophobia, color blindness, severe hearing impairment, weight>300 lbs., wheelchair-bound, tattoos as indicated by the guidelines established by the Zuckerman Institute MRI unit: https://mr.research.columbia.edu/

2. DSM 5 diagnoses of schizophrenia, schizoaffective disorder, or bipolar disorder

3. Any non-AUD psychiatric disorder that may, according to the investigator's judgment, require treatment over the course of the study

4. Significant suicide or violence risk

5. Currently taking psychotropic medication

6. Current substance use disorder other than AUD, tobacco use disorder or mild cannabis use disorder

7. Currently pregnant, attempting to become pregnant or nursing

8. Sufficiently socially unstable as to preclude participation (e.g. homeless).

9. Known history of allergy, intolerance, or hypersensitivity to disulfiram or its derivates

10. Contraindications to disulfiram treatment (e.g. liver disease, kidney disease, cardiac disease, seizure disorder, hypothyroidism, diabetes mellitus, pregnancy or lactation, allergy to disulfiram or thiuram derivatives)

11. Currently taking medications containing alcohol, metronidazole, isoniazid, paraldehyde, phenytoin, warfarin, or theophylline.

12. Treatment with concomitant medications that might interfere with disulfiram

13. A history of alcohol withdrawal seizures, delirium tremens or resistant alcohol withdrawal

14. Current moderate or severe alcohol withdrawal (CIWA >9 with BAL<0.05)

15. History of prior disulfiram treatment failure

16. Being abstinent for > 7 days at the time of screening

1. Neurological, medical or other conditions that would interfere with MRI scanning (e.g., history of stroke, seizure, brain tumor, brain infection, traumatic brain injury, multiple sclerosis, dementia, non MRI-compliant metal device in body, pregnancy, claustrophobia, color blindness, severe hearing impairment, weight>300 lbs., wheelchair- bound, tattoos as indicated by the guidelines established by the ZI MRI unit: https://mr.research.columbia.edu/

2. DSM 5 diagnoses of schizophrenia, schizoaffective disorder, or bipolar disorder

3. Any psychiatric disorder that may, according to the investigator's judgment, require treatment over the course of the study

4. Significant suicide or violence risk

5. Currently taking psychotropic medication

6. Current substance use disorder other than tobacco use disorder or mild cannabis use disorder

7. Currently pregnant, attempting to become pregnant or nursing

8. Sufficiently socially unstable as to preclude participation (e.g., homeless).

9. A diagnosis of AUD of any severity

• Minimum Eligible Age: 21 Years
• Maximum Eligible Age: 39 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

NIH

Sponsor Role: collaborator

Columbia University

OTHER

Sponsor Role: lead

Responsible Party

A. Benjamin Srivastava

Assistant Professor of Clinical Psychiatry

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Columbia University Irving Medical Center

New York, New York, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

A B Srivastava, MD

Role: CONTACT

abs2257@cumc.columbia.edu

646-774-8189

Facility Contacts

A B Srivastava, MD

Role: primary

abs2257@cumc.columbia.edu

646-774-8189

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Other Identifiers

K23AA030355

Identifier Type: NIH

Identifier Source: secondary_id

View Link

AAAV4012

Identifier Type: -

Identifier Source: org_study_id