Neural Mechanisms of Disulfiram Effects

NCT02735577 | Completed Phase 4 Results DMC

• 1 other identifier: 7193
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

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.

Conditions

Alcohol Use Disorder

Keywords

Alcohol; Craving; Functional MRI; Cognitive control; Risky decision-making; Disulfiram

Outcome Measures

Primary Outcomes (1)

• Alcohol Use

  Number of drinking days

  42 days

Study Arms (1)

Disulfiram

EXPERIMENTAL

Patients in this arm will receive disulfiram 250 mg daily for a total of 40 days.

Drug: Disulfiram

Interventions

Disulfiram DRUG

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.

Also known as: Antabuse

Disulfiram

Eligibility Criteria

• Age: 21 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• New York State Psychiatric Institute: lead

Study Sites (1)

NYPInstitute

New York, New York, 10032, United States

Location

Related Publications (1)

• 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.

  PMID: 35285015 DERIVED

MeSH Terms

Conditions

Alcoholism

Interventions

Disulfiram

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

Limitations and Caveats

fMRI data analysis is not complete because there are not enough subjects to produce valid data.

Results Point of Contact

• Title: Nasir Naqvi, MD
• Organization: New York State Psychiatric Institute

nasir.naqvi@nyspi.columbia.edu

6467748181

Study Officials

• Nasir H. Naqvi, MD, PhD

  NYP Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: research psychiatrist

Study Record Dates

• First Submitted: April 6, 2016
• First Posted: April 12, 2016
• Study Start: March 1, 2016
• Primary Completion: October 31, 2019
• Study Completion: October 16, 2020
• Last Updated: November 23, 2020
• Results First Posted: November 23, 2020

Record last verified: 2020-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)