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Neural Mechanisms of Disulfiram Effects

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ClinicalTrials.gov Identifier: NCT02735577
Recruitment Status : Recruiting
First Posted : April 12, 2016
Last Update Posted : March 6, 2019
Sponsor:
Information provided by (Responsible Party):
Nasir Naqvi, New York State Psychiatric Institute

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.

Condition or disease Intervention/treatment Phase
Alcohol Use Disorder Drug: Disulfiram Phase 4

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Neurocognitive Mechanisms of Disulfiram Treatment of Alcohol Use Disorder
Study Start Date : March 2016
Estimated Primary Completion Date : March 2020
Estimated Study Completion Date : March 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Alcohol
Drug Information available for: Disulfiram

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 Name: Antabuse




Primary Outcome Measures :
  1. Alcohol use [ Time Frame: 40 days ]
    Number of drinking days



Information from the National Library of Medicine

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Ages Eligible for Study:   21 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02735577


Contacts
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Contact: Nasir H. Naqvi, MD, PhD (212) 923-3031

Locations
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United States, New York
NYPInstitute Recruiting
New York, New York, United States, 10032
Contact: Nasir H. Naqvi, MD, PhD    212-923-3031    nhn2102@columbia.edu   
Principal Investigator: Nasir H. Naqvi, MD, PhD         
Sponsors and Collaborators
New York State Psychiatric Institute
Investigators
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Principal Investigator: Nasir H. Naqvi, MD, PhD NYP Institute

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Responsible Party: Nasir Naqvi, research psychiatrist, New York State Psychiatric Institute
ClinicalTrials.gov Identifier: NCT02735577     History of Changes
Other Study ID Numbers: 7193
First Posted: April 12, 2016    Key Record Dates
Last Update Posted: March 6, 2019
Last Verified: March 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Nasir Naqvi, New York State Psychiatric Institute:
Alcohol
Craving
Functional MRI
Cognitive control
Risky decision-making
Disulfiram

Additional relevant MeSH terms:
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Alcohol Drinking
Alcoholism
Drinking Behavior
Alcohol-Related Disorders
Substance-Related Disorders
Chemically-Induced Disorders
Mental Disorders
Disulfiram
Alcohol Deterrents
Acetaldehyde Dehydrogenase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action