Genetic and Brain Mechanisms of Naltrexone's Treatment Efficacy for Alcoholism



Status:Completed
Conditions:Psychiatric
Therapuetic Areas:Psychiatry / Psychology
Healthy:No
Age Range:18 - 70
Updated:7/12/2018
Start Date:June 2009
End Date:December 2015

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Genetic and Brain Mechanisms of Naltrexone?s Treatment Efficacy for Alcoholism

The overarching aim of this trial is to evaluate naltrexone's efficacy in light of genetic
variation and brain response to alcohol cues utilizing a neuroimaging paradigm. This trial
has four specific aims. First, this trial will evaluate whether the presence of the OPRM1
Asp40 allele substitution is associated with improved treatment response to naltrexone in
treatment-seeking alcoholics. Second, it will evaluate whether there is a difference in the
naltrexone dampening of the alcohol cue-induced brain activation dependent on OPRM1 genotype.
Third, it will explore whether alcohol cue-induced brain activation dampening by naltrexone
might be a mediating factor in the treatment effects of naltrexone, the OPRM1 gene, or their
interaction that might be observed in the first aim. Finally, this trial will evaluate the
effect of medication compliance, or adverse effects, on the observed medication by genotype
treatment response. A secondary aim will measure medication compliance and side effects based
on OPRM1 genotype.


Inclusion Criteria

1. Age 18 70

2. Subjects will meet criteria for primary alcohol dependence

3. Consumes, on average, at least 5 standard drinks per day for men and 4 drinks per day
for women in the 90 days pre-screening. Has at least 50% of days as heavy drinking
days (as defined above).

4. Able to maintain sobriety for four days (with or without the aid of alcohol
detoxification medications) as determined by self report and breathalyzer measurements

5. Able to read and understand questionnaires and informed consent

6. Lives within approximately 50 miles of the study site

Exclusion Criteria

1. Currently meets DSM IV criteria for any other psychoactive substance dependence
disorder except nicotine dependence

2. Any psychoactive substance abuse, except marijuana, nicotine, and cocaine, within the
last 30 days as evidenced by subject report, collateral report, or urine drug screen.
May meet cocaine abuse criteria, but not dependence, and also must have two sequential
urines free of illicit substances

3. Meets DSM IV criteria for current and active axis I disorders of major depression,
panic disorder, obsessive compulsive disorder, post traumatic stress syndrome, bipolar
affective disorder, schizophrenia, or any other psychotic disorder or organic mental
disorder

4. Meets DSM IV current criteria for dissociative disorder or eating disorders

5. Has current suicidal ideation or homicidal ideation

6. Need for maintenance or acute treatment with any psychoactive medication, except a
stable dose (at least one month) of antidepressants

7. Need for maintenance on anti-seizure medications (including topiramate and gabapentin)

8. Use of disulfiram, acamprosate, or naltrexone in the last two weeks

9. Clinically significant medical problems such as cardiovascular, renal, GI, or
endocrine problem that would impair participation or limit medication ingestion

10. Hepatocellular disease indicated by elevations of SGPT (ALT) and SGOT (AST) of at
least 3.0 times normal at screening and/or after 5 days abstinence

11. Sexually active female of child-bearing potential who is pregnant (by urine HCG),
nursing, or who is not willing to use a reliable form of birth control

12. Has current charges pending for a violent crime (not including DUI-related offenses)

13. Does not have a stable living situation

14. African American heritage due to low prevalence of Asp40 (also see Inclusion of Women
and Minorities section)

Exclusion Criteria of fMRI Procedure

1. Having metal objects in the body that are deemed unsafe in the MRI environment.

2. Severe claustrophobia that cannot be managed with support and encouragement.

3. Morbid obesity such that placement in the MRI scanner is impossible.

4. History of significant head injury leading to unconsciousness.
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