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| ID | Type | Description | Link |
|---|---|---|---|
| K23AA030355 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Institute on Alcohol Abuse and Alcoholism (NIAAA) | NIH |
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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:
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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
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| 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Disulfiram 250 mg | Drug | Disulfiram will be used in Participants with Alcohol Use Disorder only to facilitate abstinence. |
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| Measure | Description | Time Frame |
|---|---|---|
| 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 |
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Inclusion Criteria (Participants with Alcohol use Disorder):
Inclusion Criteria (Healthy Volunteer Participants):
Exclusion Criteria (Participants with Alcohol use Disorder):
Exclusion Criteria (Healthy Volunteer Participants):
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| A B Srivastava, MD | Contact | 646-774-8189 | abs2257@cumc.columbia.edu |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Columbia University Irving Medical Center | Recruiting | New York | New York | 10019 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 26718394 | Background | 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. | |
| 31886106 | 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. |
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fMRI data and metadata will be archived in OpenNeuro, and Electrodermal Activity data will be stored in the DANDI archive and deposited to NIAAA Data Archive (NIAAADA), which is part of the NIMH NDA. All data will be de-identified prior to receipt by the repository, but the information needed to generate a global unique identifier for the NIAAADA, which is part of the NIMH NDA, will be collected for each subject. Sufficient data from this project will be preserved to enable sharing via NIAAADA data of sufficient quality to validate and replicate research findings. NIAAA requires data measured from human subjects to be shared using the NIAAADA. All fMRI resting state and task related paradigm designs and experiment definitions will be deposited in the NIAAADA. Studies will be created that contain the data used for every publication. Sufficient data from this project will be preserved to enable sharing via NDA data of sufficient quality to validate and replicate research findings.
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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.
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
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| ID | Term |
|---|---|
| D000437 | Alcoholism |
| D001008 | Anxiety Disorders |
| ID | Term |
|---|---|
| D019973 | Alcohol-Related Disorders |
| D019966 | Substance-Related Disorders |
| D064419 | Chemically-Induced Disorders |
| D001523 | Mental Disorders |
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| ID | Term |
|---|---|
| D004221 | Disulfiram |
| D008279 | Magnetic Resonance Imaging |
| ID | Term |
|---|---|
| D004050 | Ditiocarb |
| D013859 | Thiocarbamates |
| D002219 | Carbamates |
| D000144 | Acids, Acyclic |
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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.
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| 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. |
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| D002264 |
| Carboxylic Acids |
| D009930 | Organic Chemicals |
| D004220 | Disulfides |
| D013440 | Sulfides |
| D013457 | Sulfur Compounds |
| D014054 | Tomography |
| D003952 | Diagnostic Imaging |
| D019937 | Diagnostic Techniques and Procedures |
| D003933 | Diagnosis |