Anxiety During Abstinence in AUD

NCT06793488 | Recruiting Early Phase 1 DMC FDA Drug

• 2 other identifiers: AAAV4012K23AA030355
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

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. 1.To characterize anxiety itself as well as anxiety related-neurobiological circuitry in early abstinence in AUD
2. 2.To examine how anxiety and anxiety related-neurobiological circuitry change over the course of abstinence in AUD

Conditions

Alcohol Use Disorder

Keywords

fMRI; disulfiram; withdrawal; anxiety; abstinence

Outcome Measures

Primary Outcomes (3)

• AI-BNST Resting state functional connectivity correlation (R) value

  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.

  1 week and 3 months

• AI-BNST task activation t statistic

  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

  1 week and 3 months

• State trait anxiety inventory score

  The State-Trait Anxiety Inventory (STAI) score ranges from 20-80, with higher scores indicating greater anxiety

  1 week and 3 months

Study Arms (2)

Participants with Alcohol Use Disorder

EXPERIMENTAL

Participants with Alcohol Use Disorder (AUDP) will be participants (n=40) ages 21-55 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.

Drug: Disulfiram 250 mg; Diagnostic Test: functional MRI

Healthy volunteer participants

OTHER

Healthy volunteer participants will be participants (n=20) ages 21-55 without a history of alcohol or other substance use disorders. They will undergo fMRI scanning once.

Diagnostic Test: functional MRI

Interventions

Disulfiram 250 mg DRUG

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

Also known as: antabuse

Participants with Alcohol Use Disorder

functional MRI 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.

Also known as: fMRI

Healthy volunteer participants; Participants with Alcohol Use Disorder

Eligibility Criteria

• Age: 21 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Between the ages of 21 and 55
• Right-handed
• Able to perform informed consent and comply with study
• Seeking treatment for AUD
• Meets The Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria for AUD of at least moderate severity (\>3 symptoms)
• Between the ages of 21 and 55
• Right-handed
• Able to perform informed consent and comply with study
• 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.

You may not qualify if:

• 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/
• DSM 5 diagnoses of schizophrenia, schizoaffective disorder, or bipolar disorder
• Any non-AUD psychiatric disorder that may, according to the investigator's judgment, require treatment over the course of the study
• Significant suicide or violence risk
• Currently taking psychotropic medication
• Current substance use disorder other than AUD, tobacco use disorder or mild cannabis use disorder
• Currently pregnant, attempting to become pregnant or nursing
• Sufficiently socially unstable as to preclude participation (e.g. homeless).
• Known history of allergy, intolerance, or hypersensitivity to disulfiram or its derivates
• 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)
• Currently taking medications containing alcohol, metronidazole, isoniazid, paraldehyde, phenytoin, warfarin, or theophylline.
• Treatment with concomitant medications that might interfere with disulfiram
• A history of alcohol withdrawal seizures, delirium tremens or resistant alcohol withdrawal
• Current moderate or severe alcohol withdrawal (CIWA \>9 with BAL\<0.05)
• History of prior disulfiram treatment failure

Sponsors & Collaborators

• Columbia University: lead
• National Institute on Alcohol Abuse and Alcoholism (NIAAA): collaborator

Study Sites (1)

Columbia University Irving Medical Center

New York, New York, 10019, United States

RECRUITING

Related Publications (18)

• Anker JJ, Kushner MG, Thuras P, Menk J, Unruh AS. Drinking to cope with negative emotions moderates alcohol use disorder treatment response in patients with co-occurring anxiety disorder. Drug Alcohol Depend. 2016 Feb 1;159:93-100. doi: 10.1016/j.drugalcdep.2015.11.031. Epub 2015 Dec 11.

  PMID: 26718394 BACKGROUND

• Anker JJ, Kushner MG. Co-Occurring Alcohol Use Disorder and Anxiety: Bridging Psychiatric, Psychological, and Neurobiological Perspectives. Alcohol Res. 2019 Dec 30;40(1):arcr.v40.1.03. doi: 10.35946/arcr.v40.1.03. eCollection 2019.

  PMID: 31886106 BACKGROUND

• Glasser MF, Coalson TS, Robinson EC, Hacker CD, Harwell J, Yacoub E, Ugurbil K, Andersson J, Beckmann CF, Jenkinson M, Smith SM, Van Essen DC. A multi-modal parcellation of human cerebral cortex. Nature. 2016 Aug 11;536(7615):171-178. doi: 10.1038/nature18933. Epub 2016 Jul 20.

  PMID: 27437579 BACKGROUND

• Brown SA, Irwin M, Schuckit MA. Changes in anxiety among abstinent male alcoholics. J Stud Alcohol. 1991 Jan;52(1):55-61. doi: 10.15288/jsa.1991.52.55.

  PMID: 1994124 BACKGROUND

• Centanni SW, Morris BD, Luchsinger JR, Bedse G, Fetterly TL, Patel S, Winder DG. Endocannabinoid control of the insular-bed nucleus of the stria terminalis circuit regulates negative affective behavior associated with alcohol abstinence. Neuropsychopharmacology. 2019 Feb;44(3):526-537. doi: 10.1038/s41386-018-0257-8. Epub 2018 Nov 2.

  PMID: 30390064 BACKGROUND

• Clauss JA, Avery SN, Benningfield MM, Blackford JU. Social anxiety is associated with BNST response to unpredictability. Depress Anxiety. 2019 Aug;36(8):666-675. doi: 10.1002/da.22891. Epub 2019 Apr 6.

  PMID: 30953446 BACKGROUND

• Agarwal R, Sharma SK, Malaviya AN. Gold-induced hypersensitivity pneumonitis in a patient with rheumatoid arthritis. Clin Exp Rheumatol. 1989 Jan-Feb;7(1):89-90.

  PMID: 2706825 BACKGROUND

• Driessen M, Meier S, Hill A, Wetterling T, Lange W, Junghanns K. The course of anxiety, depression and drinking behaviours after completed detoxification in alcoholics with and without comorbid anxiety and depressive disorders. Alcohol Alcohol. 2001 May-Jun;36(3):249-55. doi: 10.1093/alcalc/36.3.249.

  PMID: 11373263 BACKGROUND

• Farb NA, Segal ZV, Anderson AK. Attentional modulation of primary interoceptive and exteroceptive cortices. Cereb Cortex. 2013 Jan;23(1):114-26. doi: 10.1093/cercor/bhr385. Epub 2012 Jan 19.

  PMID: 22267308 BACKGROUND

• Flook EA, Feola B, Avery SN, Winder DG, Woodward ND, Heckers S, Blackford JU. BNST-insula structural connectivity in humans. Neuroimage. 2020 Apr 15;210:116555. doi: 10.1016/j.neuroimage.2020.116555. Epub 2020 Jan 16.

  PMID: 31954845 BACKGROUND

• Joutsa J, Moussawi K, Siddiqi SH, Abdolahi A, Drew W, Cohen AL, Ross TJ, Deshpande HU, Wang HZ, Bruss J, Stein EA, Volkow ND, Grafman JH, van Wijngaarden E, Boes AD, Fox MD. Brain lesions disrupting addiction map to a common human brain circuit. Nat Med. 2022 Jun;28(6):1249-1255. doi: 10.1038/s41591-022-01834-y. Epub 2022 Jun 13.

  PMID: 35697842 BACKGROUND

• Kushner MG, Abrams K, Thuras P, Hanson KL, Brekke M, Sletten S. Follow-up study of anxiety disorder and alcohol dependence in comorbid alcoholism treatment patients. Alcohol Clin Exp Res. 2005 Aug;29(8):1432-43. doi: 10.1097/01.alc.0000175072.17623.f8.

  PMID: 16131851 BACKGROUND

• Schuckit MA, Hesselbrock V. Alcohol dependence and anxiety disorders: what is the relationship? Am J Psychiatry. 1994 Dec;151(12):1723-34. doi: 10.1176/ajp.151.12.1723.

  PMID: 7977877 BACKGROUND

• Schuckit MA, Irwin M, Brown SA. The history of anxiety symptoms among 171 primary alcoholics. J Stud Alcohol. 1990 Jan;51(1):34-41. doi: 10.15288/jsa.1990.51.34.

  PMID: 2299847 BACKGROUND

• Skinner MD, Lahmek P, Pham H, Aubin HJ. Disulfiram efficacy in the treatment of alcohol dependence: a meta-analysis. PLoS One. 2014 Feb 10;9(2):e87366. doi: 10.1371/journal.pone.0087366. eCollection 2014.

  PMID: 24520330 BACKGROUND

• Srivastava AB, Sanchez-Pena J, Levin FR, Mariani JJ, Patel GH, Naqvi NH. Drinking reduction during cognitive behavioral therapy for alcohol use disorder is associated with a reduction in anterior insula-bed nucleus of the stria terminalis resting-state functional connectivity. Alcohol Clin Exp Res. 2021 Aug;45(8):1596-1606. doi: 10.1111/acer.14661. Epub 2021 Aug 2.

  PMID: 34342012 BACKGROUND

• Theiss JD, Ridgewell C, McHugo M, Heckers S, Blackford JU. Manual segmentation of the human bed nucleus of the stria terminalis using 3T MRI. Neuroimage. 2017 Feb 1;146:288-292. doi: 10.1016/j.neuroimage.2016.11.047. Epub 2016 Nov 19.

  PMID: 27876653 BACKGROUND

• Wilcox CE, Dekonenko CJ, Mayer AR, Bogenschutz MP, Turner JA. Cognitive control in alcohol use disorder: deficits and clinical relevance. Rev Neurosci. 2014;25(1):1-24. doi: 10.1515/revneuro-2013-0054.

  PMID: 24361772 BACKGROUND

MeSH Terms

Conditions

Alcoholism; Anxiety Disorders

Interventions

Disulfiram; Magnetic Resonance Imaging

Condition Hierarchy (Ancestors)

Alcohol-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Ditiocarb; Thiocarbamates; Carbamates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Disulfides; Sulfides; Sulfur Compounds; Tomography; Diagnostic Imaging; Diagnostic Techniques and Procedures; Diagnosis

Central Study Contacts

A B Srivastava, MD

CONTACT

646-774-8189; abs2257@cumc.columbia.edu

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Clinical Psychiatry

Model Details: Participants with alcohol use disorder (n=40) will be administered disulfiram for 3 months, which will serve to facilitate abstinence from alcohol in order to study the mechanisms of anxiety during early and protracted abstinence in alcohol use disorder. The will undergo fMRI scanning after 1 week and 3 months of disulfiram. Participants will be observed taking disulfiram both remotely (4/5 work days/week) and in person 1 day/week. Healthy volunteer participants (n=20) will not receive disufiram and will only be scanned once.

Study Record Dates

• First Submitted: January 21, 2025
• First Posted: January 27, 2025
• Study Start: September 15, 2025
• Primary Completion (Estimated): August 30, 2029
• Study Completion (Estimated): August 30, 2029
• Last Updated: February 10, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Time Frame: Data will be desposited after 12 months, uploaded every 6 months thereafter. The research community will have access to data. NIAAADA/NDA will make decisions about how long to preserve the data, but that data archive has not deleted any deposited data up to now.
• Access Criteria: To request access of the data, researchers will use the standard processes at NIAAADA/NDA, and the NIAAADA/NDA Data Access Committee will decide which requests to grant. fMRI data will be publically available in OpenNeuro

Locations

US (1)