Back to resultsNeural Mechanisms of Disulfiram Effects
Primary Purpose
Alcohol Use Disorder
Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Disulfiram
Sponsored by
About this trial
This is an interventional basic science trial for Alcohol Use Disorder focused on measuring Alcohol, Craving, Functional MRI, Cognitive control, Risky decision-making, Disulfiram
Eligibility Criteria
Inclusion Criteria:
- Between the ages of 21-60
- Right-handed
- Capable of giving informed consent and complying with study procedures
- Reports drinking a minimum of 5 standard drinks for men or 4 standard drinks for women on at least 4 days per week on average over the past 28 days
- Meets DSM-V criteria for current Alcohol Use Disorder
- Seeking treatment for Alcohol Use Disorder
- Agree to not seek additional treatment, apart from Alcoholics Anonymous
- Willing to attempt to abstain from alcohol completely for the duration of the study
- Willing to be hospitalized on a research unit for 24 hours, longer if detoxification is needed.
Exclusion Criteria:
- Risk of severe alcohol withdrawal (e.g. history of seizures or delirium tremens)
- Current Moderate or Severe Substance Use Disorder, other than Alcohol, Nicotine or Caffeine Use Disorders
- Lifetime history of Bipolar Disorder, Schizophrenia or Schizoaffective Disorder
- Any current psychiatric disorder, other than Alcohol Use Disorder, that, in the judgment of the investigator, will require treatment that will interfere with study participation.
- Current severe depression (HAM-D >24) or anxiety (HAM-A >24)
- Significant suicide or violence risk
- Currently taking any psychotropic medications
- Legally mandated to participate in treatment
- History of prior treatment with disulfiram
- Sufficiently socially unstable as to preclude participation (e.g. homeless)
- Contraindications to disulfiram treatment (liver disease, kidney disease, cardiac disease, seizure disorder, hypothyroidism, diabetes mellitus, pregnancy or lactation, allergy to disulfiram or thiuran derivatives)
- Neurological or medical conditions that would interfere with MRI scanning (e.g. history of stroke, seizure, brain tumor, brain infection, traumatic brain injury, multiple sclerosis, dementia, metal device in body, pregnancy, claustrophobia, color blindness, severe hearing impairment, weight>300 lbs., wheelchair-bound)
- Currently taking medications containing alcohol, metronidazole, isoniazid, paraldehyde, phenytoin, warfarin, or theophylline.
- Significant alcohol withdrawal (CIWA>8) at screening, after confirming a blood alcohol level of zero.
Sites / Locations
- NYPInstitute
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Disulfiram
Arm Description
Patients in this arm will receive disulfiram 250 mg daily for a total of 40 days.
Outcomes
Primary Outcome Measures
Alcohol Use
Number of drinking days
Secondary Outcome Measures
Full Information
NCT ID
NCT02735577
First Posted
April 6, 2016
Last Updated
October 29, 2020
Sponsor
New York State Psychiatric Institute
1. Study Identification
Unique Protocol Identification Number
NCT02735577
Brief Title
Neural Mechanisms of Disulfiram Effects
Official Title
Neurocognitive Mechanisms of Disulfiram Treatment of Alcohol Use Disorder
Study Type
Interventional
2. Study Status
Record Verification Date
October 2020
Overall Recruitment Status
Completed
Study Start Date
March 2016 (undefined)
Primary Completion Date
October 31, 2019 (Actual)
Study Completion Date
October 16, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
New York State Psychiatric Institute
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This study combines functional MRI with medication treatment in order to understand the neural mechanisms by which disulfiram, a currently approved medication for alcohol use disorder, changes behavior. Disulfiram is a medication that prevents drinking by causing a highly unpleasant physical reaction when alcohol is consumed while it is being taken. Thus, it provides a means for studying the general neural mechanisms by which awareness of risks impacts behavior change in alcohol use disorder.
Detailed Description
The overall goal of this project is to combine functional brain imaging and clinical methods in order to examine how treatment with disulfiram (DIS) alters neural activity related to alcohol-seeking motivation in patients with alcohol use disorder (AUD). DIS is an established, effective, FDA-approved medication for AUD that causes a highly aversive physical reaction if alcohol is consumed while it is being taken. The mere awareness of the risk or threat the DIS-alcohol reaction deters alcohol use, i.e. it is not necessary to drink alcohol while taking DIS to change behavior. By uncovering the neural mechanisms underlying this risk/threat-based psychological effect, it will be possible to integrate DIS with biologically based treatments targeted at these neural mechanisms, with the goal of improving the efficacy of DIS. Furthermore, the results will shed light on the general neural mechanisms by which awareness of risks of substance use impacts addictive motivation. This is a core process in a number of behavioral treatments for substance use disorders, such as Motivational Interviewing and Contingency Management, as well as in behavior change in non-treatment settings.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Alcohol Use Disorder
Keywords
Alcohol, Craving, Functional MRI, Cognitive control, Risky decision-making, Disulfiram
7. Study Design
Primary Purpose
Basic Science
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
7 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Disulfiram
Arm Type
Experimental
Arm Description
Patients in this arm will receive disulfiram 250 mg daily for a total of 40 days.
Intervention Type
Drug
Intervention Name(s)
Disulfiram
Other Intervention Name(s)
Antabuse
Intervention Description
Patients will be hospitalized on an inpatient psychiatric unit for 1-7 days to initiate abstinence. An fMRI scan will be performed to examine neural mechanisms of alcohol motivation. Prior to discharge, patients will receive the first dose of disulfiram 500 mg. They will then attend an outpatient clinic every other day for 14 days. At each clinic visit, they will receive 500 mg of disulfiram under supervision. Another fMRI scan examining alcohol motivation will be performed. Following this, all patients will attend the clinic weekly, and will be prescribed disulfiram 250 mg daily to take at home. This will be followed followed by an optional extension of weekly visits taking disulfiram 250 mg daily for another 28 days, for a total of 70 days of disulfiram treatment.
Primary Outcome Measure Information:
Title
Alcohol Use
Description
Number of drinking days
Time Frame
42 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
21 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Between the ages of 21-60
Right-handed
Capable of giving informed consent and complying with study procedures
Reports drinking a minimum of 5 standard drinks for men or 4 standard drinks for women on at least 4 days per week on average over the past 28 days
Meets DSM-V criteria for current Alcohol Use Disorder
Seeking treatment for Alcohol Use Disorder
Agree to not seek additional treatment, apart from Alcoholics Anonymous
Willing to attempt to abstain from alcohol completely for the duration of the study
Willing to be hospitalized on a research unit for 24 hours, longer if detoxification is needed.
Exclusion Criteria:
Risk of severe alcohol withdrawal (e.g. history of seizures or delirium tremens)
Current Moderate or Severe Substance Use Disorder, other than Alcohol, Nicotine or Caffeine Use Disorders
Lifetime history of Bipolar Disorder, Schizophrenia or Schizoaffective Disorder
Any current psychiatric disorder, other than Alcohol Use Disorder, that, in the judgment of the investigator, will require treatment that will interfere with study participation.
Current severe depression (HAM-D >24) or anxiety (HAM-A >24)
Significant suicide or violence risk
Currently taking any psychotropic medications
Legally mandated to participate in treatment
History of prior treatment with disulfiram
Sufficiently socially unstable as to preclude participation (e.g. homeless)
Contraindications to disulfiram treatment (liver disease, kidney disease, cardiac disease, seizure disorder, hypothyroidism, diabetes mellitus, pregnancy or lactation, allergy to disulfiram or thiuran derivatives)
Neurological or medical conditions that would interfere with MRI scanning (e.g. history of stroke, seizure, brain tumor, brain infection, traumatic brain injury, multiple sclerosis, dementia, metal device in body, pregnancy, claustrophobia, color blindness, severe hearing impairment, weight>300 lbs., wheelchair-bound)
Currently taking medications containing alcohol, metronidazole, isoniazid, paraldehyde, phenytoin, warfarin, or theophylline.
Significant alcohol withdrawal (CIWA>8) at screening, after confirming a blood alcohol level of zero.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Nasir H. Naqvi, MD, PhD
Organizational Affiliation
NYP Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
NYPInstitute
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
35285015
Citation
Saifi MA, Shaikh AS, Kaki VR, Godugu C. Disulfiram prevents collagen crosslinking and inhibits renal fibrosis by inhibiting lysyl oxidase enzymes. J Cell Physiol. 2022 May;237(5):2516-2527. doi: 10.1002/jcp.30717. Epub 2022 Mar 13.
Results Reference
derived
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Neural Mechanisms of Disulfiram Effects
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