Clinical trial NCT02735577
Conditions: Alcohol Use Disorder
Keywords: Alcohol Craving Functional MRI Cognitive control Risky decision-making Disulfiram
Sponsor: New York State Psychiatric Institute
Start date: 2016-03-01; Completion date: 2020-10-16
Enrollment: 7 participants; Allocation: NA; Intervention model: SINGLE_GROUP

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.

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.

Arms: arm 1: Patients in this arm will receive disulfiram 250 mg daily for a total of 40 days.
Interventions: intervention 1: Disulfiram
Intervention descriptions: intervention 1: 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.

Protocol documents:
Prot_000.pdf: 
Study: # 7193 entitled NEUROCOGNITIVE MECHANISMS OF DISULFIRAM TREATMENT OF ALCOHOL USE 
DISORDER 
 
PI: Nasir Naqvi, MD, PhD 
NCT# NCT02735577 
Study Protocol Date: January 26, 2016 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 





























































SAP_001.pdf: 
Study: # 7193 entitled NEUROCOGNITIVE MECHANISMS OF DISULFIRAM TREATMENT OF ALCOHOL USE 
DISORDER 
 
PI: Nasir Naqvi, MD, PhD 
NCT# NCT02735577 
Data Analysis Plan created: November 14, 2014 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
Data Analysis: Functional images will be pre-processed according to standard procedures. A 
whole-brain general linear model analysis will examine effects of time-point (pre-DIS vs. post-
DIS) and cue-type (alcohol vs. food), as well as interaction effects. Psychophysiological 
interaction analysis will examine cue-elicited functional connectivity between the VS and its 
inputs from the insula, VMPFC and DLPFC, and how these are changed from pre- to post-DIS. 
Statistical mediation analyses will determine the extent to which these changes are mediated by 
the perceived likelihood and salience of the DIS alcohol reaction. Logistic regression analysis 
will be used to determine whether post-DIS cue-induced VS activity predicts drinking during 1 
month of DIS, after controlling for pre-DIS cue-induced VS activity, as well as for AUD severity, 
motivation, risk-taking, insight and impulsivity.