Anxiety during abstinence in people with alcohol use disorder

Neural Mechanisms of Anxiety During Early and Protracted Abstinence in Alcohol Use Disorder

This project will test whether anxiety and related brain activity change from early to three months of abstinence in people with alcohol use disorder who take disulfiram, compared with healthy volunteers.

Quick facts

• Phase: Early Phase 1
• Study type: Interventional
• Enrollment: 60 (estimated)
• Ages: 21 Years to 55 Years
• Sex: All
• Sponsor: Columbia University (Academic / other)
• Locations: 1 site (New York, New York)
• Trial ID: NCT06793488 on ClinicalTrials.gov

What this trial studies

Researchers will recruit 40 people seeking treatment for moderate-or-worse alcohol use disorder and 20 age-matched healthy volunteers. Participants with AUD will be started on disulfiram and undergo fMRI scanning twice—about 8–14 days after their last drink and again after three months of abstinence—while healthy volunteers will have a single fMRI scan. fMRI will include an anxiety-evoking task that probes anticipation of uncertain threat plus resting-state scans to measure connectivity among the anterior insula, bed nucleus of the stria terminalis, and dorsolateral prefrontal cortex. The study will relate changes in circuit activity and connectivity to changes in current anxiety symptoms over abstinence.

Who should consider this trial

Good fit: Adults aged 21–55 seeking treatment for moderate-or-worse AUD who are right-handed, able to consent, willing to take disulfiram, and able to complete two MRI visits.

Not a fit: People who are pregnant, have MRI contraindications or significant neurological/medical conditions, cannot take disulfiram, or are unwilling to undergo repeated scans are unlikely to benefit or be eligible.

Why it matters

Potential benefit: If successful, the findings could identify brain circuit changes that drive abstinence-related anxiety and point to targets for treatments that reduce relapse risk.

How similar studies have performed: Previous fMRI studies have linked the anterior insula, BNST, and DLPFC to anxiety and addiction, but longitudinal imaging across early and protracted abstinence while using disulfiram is relatively novel.

Eligibility criteria

Inclusion Criteria (Participants with Alcohol use Disorder):

1. Between the ages of 21 and 55
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)

Inclusion Criteria (Healthy Volunteer Participants):

1. Between the ages of 21 and 55
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 (Participants with Alcohol use Disorder):

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

Exclusion Criteria (Healthy Volunteer Participants):

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

Where this trial is running

New York, New York

• Columbia University Irving Medical Center — New York, New York, United States (Recruiting)

Study contacts

• Study coordinator: A B Srivastava, MD

Conditions Alcohol Use Disorder; fMRI; disulfiram; withdrawal; anxiety; abstinence