Neural Mechanisms of Disulfiram Effects

• Sponsor: New York State Psychiatric Institute (Other)
• Overall Status: Completed
• CT.gov ID: NCT02735577
• Collaborator: (none)
• Enrollment: 7
• Location: 1
• Arm: 1
• Duration (Months): 55.5
• Patients Per Site Per Month: 0.1

Study Details

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.

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 7 participants
• Allocation: N/A
• 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: Mar 1, 2016
• Actual Primary Completion Date: Oct 31, 2019
• Actual Study Completion Date: Oct 16, 2020

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Alcohol Use [42 days]

   Number of drinking days

Eligibility Criteria

Criteria

• Ages Eligible for Study: 21 Years to 60 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	NYPInstitute	New York	New York	United States	10032

Sponsors and Collaborators

• New York State Psychiatric Institute

Investigators

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

Study Documents (Full-Text)

• Study Protocol - Jan 26, 2016
• Statistical Analysis Plan - Nov 14, 2014

More Information

Publications

None provided.

• Responsible Party: Nasir Naqvi, research psychiatrist, New York State Psychiatric Institute
• ClinicalTrials.gov Identifier: NCT02735577
• Other Study ID Numbers: 7193
• First Posted: Apr 12, 2016
• Last Update Posted: Nov 23, 2020
• Last Verified: Oct 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Nasir Naqvi, research psychiatrist, New York State Psychiatric Institute: Alcohol; Craving; Functional MRI; Cognitive control; Risky decision-making; Disulfiram
• Additional relevant MeSH terms: Alcoholism; Alcohol Drinking; Disulfiram

Study Results

Participant Flow

Arm/Group Title	Disulfiram
Arm/Group Description	Patients in this arm will receive disulfiram 250 mg daily for a total of 42 days. 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.
Period Title: Disulfiram Treatment
STARTED	7
COMPLETED	6
NOT COMPLETED	1
Period Title: Disulfiram Treatment
STARTED	6
COMPLETED	4
NOT COMPLETED	2

Baseline Characteristics

Arm/Group Title	Disulfiram
Arm/Group Description	Patients in this arm will receive disulfiram 250 mg daily for a total of 42 days. 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.
Overall Participants	7
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	47.6 (10.4)
Sex: Female, Male (Count of Participants)
Female	3 42.9%
Male	4 57.1%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	2 28.6%
Not Hispanic or Latino	5 71.4%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	4 57.1%
White	2 28.6%
More than one race	0 0%
Unknown or Not Reported	1 14.3%
Region of Enrollment (participants) [Number]
United States	7 100%
Baseline Drinking days (prior 28 days) (days) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [days]	24.0 (2.3)

Outcome Measures

1. Primary Outcome

Title	Alcohol Use
Description	Number of drinking days
Time Frame	42 days

Outcome Measure Data

Analysis Population Description

Participants who completed the initial 42 days of disulfiram treatment

Arm/Group Title	Disulfiram
Arm/Group Description	Patients in this arm will receive disulfiram 250 mg daily for a total of 42 days. 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.
Measure Participants	6
Mean (Standard Deviation) [days]	0 (0)

Adverse Events

Time Frame	42 days of initial disulfiram treatment or length of participation
Arm/Group Title	Disulfiram
Arm/Group Description	Patients in this arm will receive disulfiram 250 mg daily for a total of 42 days. 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.
All Cause Mortality
	Disulfiram
	Affected / at Risk (%)	# Events
Total	0/7 (0%)
Serious Adverse Events
	Disulfiram
	Affected / at Risk (%)	# Events
Total	0/7 (0%)
Other (Not Including Serious) Adverse Events
	Disulfiram
	Affected / at Risk (%)	# Events
Total	0/7 (0%)

Limitations/Caveats

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

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.