Neural Mechanisms of Disulfiram Effects

October 29, 2020 updated by: Nasir Naqvi, New York State Psychiatric Institute

Neurocognitive Mechanisms of Disulfiram Treatment of Alcohol Use Disorder

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

7

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New York
      • New York, New York, United States, 10032
        • NYPInstitute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

19 years to 58 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Between the ages of 21-60
  2. Right-handed
  3. Capable of giving informed consent and complying with study procedures
  4. 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
  5. Meets DSM-V criteria for current Alcohol Use Disorder
  6. Seeking treatment for Alcohol Use Disorder
  7. Agree to not seek additional treatment, apart from Alcoholics Anonymous
  8. Willing to attempt to abstain from alcohol completely for the duration of the study
  9. Willing to be hospitalized on a research unit for 24 hours, longer if detoxification is needed.

Exclusion Criteria:

  1. Risk of severe alcohol withdrawal (e.g. history of seizures or delirium tremens)
  2. Current Moderate or Severe Substance Use Disorder, other than Alcohol, Nicotine or Caffeine Use Disorders
  3. Lifetime history of Bipolar Disorder, Schizophrenia or Schizoaffective Disorder
  4. 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.
  5. Current severe depression (HAM-D >24) or anxiety (HAM-A >24)
  6. Significant suicide or violence risk
  7. Currently taking any psychotropic medications
  8. Legally mandated to participate in treatment
  9. History of prior treatment with disulfiram
  10. Sufficiently socially unstable as to preclude participation (e.g. homeless)
  11. Contraindications to disulfiram treatment (liver disease, kidney disease, cardiac disease, seizure disorder, hypothyroidism, diabetes mellitus, pregnancy or lactation, allergy to disulfiram or thiuran derivatives)
  12. 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)
  13. Currently taking medications containing alcohol, metronidazole, isoniazid, paraldehyde, phenytoin, warfarin, or theophylline.
  14. Significant alcohol withdrawal (CIWA>8) at screening, after confirming a blood alcohol level of zero.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Disulfiram
Patients in this arm will receive disulfiram 250 mg daily for a total of 40 days.
Drug: Disulfiram
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.
Other Names:
  • Antabuse

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Alcohol Use
Time Frame: 42 days
Number of drinking days
42 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

New York State Psychiatric Institute

Investigators

  • Principal Investigator: Nasir H. Naqvi, MD, PhD, NYP Institute

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2016

Primary Completion (Actual)

October 31, 2019

Study Completion (Actual)

October 16, 2020

Study Registration Dates

First Submitted

April 6, 2016

First Submitted That Met QC Criteria

April 6, 2016

First Posted (Estimate)

April 12, 2016

Study Record Updates

Last Update Posted (Actual)

November 23, 2020

Last Update Submitted That Met QC Criteria

October 29, 2020

Last Verified

October 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 7193

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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