Neural Mechanisms of Disulfiram Effects

Alcohol Use Disorder Clinical Trial

Official title:

Neurocognitive Mechanisms of Disulfiram Treatment of Alcohol Use Disorder

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02735577
• Other study ID #: 7193
• Status: Completed
• Phase: Phase 4
• Start date: March 2016
• Est. completion date: October 16, 2020

Study information

• Verified date: October 2020
• Source: New York State Psychiatric Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 7
• Est. completion date: October 16, 2020
• Est. primary completion date: October 31, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 21 Years to 60 Years

Eligibility

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.

Related Conditions & MeSH terms

• Alcohol Drinking
• Alcohol Use Disorder
• Alcoholism

Intervention

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.

Locations

Country	Name	City	State
United States	NYPInstitute	New York	New York

Sponsors (1)

Lead Sponsor	Collaborator
New York State Psychiatric Institute

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Alcohol Use	Number of drinking days	42 days