Naltrexone and Memantine Effects on Alcohol Drinking Behaviors

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to evaluate the combined effects of the study medications naltrexone and memantine on alcohol drinking behaviors.

Detailed Description
-----------------
Participants will be randomized to receive a combination of naltrexone/memantine over a one week period and then participate in a laboratory session. During this session, participants are given an initial drink of alcohol followed by the choice to drink up to 12 more drinks over a three-hour period. These medications are hypothesized to reduce craving and number of drinks consumed prior to and after exposure to the initial drink of alcohol and during the three hour drinking period.

Official Title
-----------------
Glutamate-opioid Interactions in Alcohol Drinking Behaviors

Conditions
-----------------
Alcohol Drinking

Intervention / Treatment
-----------------
* Drug: Naltrexone and memantine first
* Drug: Naltrexone and Placebo first


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Ages 21-55 Able to read English at 6th grade level or higher and to complete study evaluations Regular alcohol drinker Exclusion Criteria: Individuals who are seeking alcohol treatment Medical conditions that would contraindicate the use of study medication Regular use of other substances

Ages Eligible for Study
-----------------
Minimum Age: 21 Years
Maximum Age: 55 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Naltrexone and memantine<br>Treatment with Naltrexone and memantine first | Drug: Naltrexone and memantine first<br>* Naltrexone 50mg memantine 20mg<br>* Other names: naltrexone's brand name is Revia;Drug: Naltrexone and Placebo first<br>* Naltrexone 50 mg Placebo<br>* Other names: naltrexone's brand name is Revia;|
| Placebo Comparator: Naltrexone and Placebo<br>Treatment with naltrexone and placebo first | Drug: Naltrexone and memantine first<br>* Naltrexone 50mg memantine 20mg<br>* Other names: naltrexone's brand name is Revia;Drug: Naltrexone and Placebo first<br>* Naltrexone 50 mg Placebo<br>* Other names: naltrexone's brand name is Revia;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Drinks Consumed at Lab Session (Day 7) | Number of drinks consumed during the lab session (Day 7) after taking study medication, ranging from 0-12. | Day 7 | 
| Craving AUC: Adlib Drinking Phase | Craving for alcohol based on Alcohol Urge Questionnaire (AUQ, Bohn et al., 1995), which is an 8 item measurement of self-reported alcohol urges that has been shown to be strongly related to alcohol dependence severity. Each item is scored from 1 (strongly disagree) to 7 (strongly agree), with a higher score indicating higher craving. Assessed multiple times, starting at 50 minutes after priming drink until 230 minutes after priming drink. Higher craving scores (ranging from 0-56) are indicated by larger log-transformed AUC. | 50-230 minutes after the priming drink during lab session | 
| Stimulation Response to Alcohol at Lab Session | Brief Biphasic Alcohol Effects Scale-Stimulation subscale (BAES; Martin et al., 1993), measuring stimulation effects of alcohol. Seven items ranging from 0 (not at all) to extremely (10) with higher measurements indicating higher stimulation. Assessed multiple times, starting at 50 minutes after priming drink until 230 minutes after priming drink. Higher stimulation scores (ranging from 0-70) are indicated by larger log-transformed AUC. | 50-230 minutes after the priming drink during lab session | 
| Sedation Response to Alcohol at Lab Session | Brief Biphasic Alcohol Effects Scale-Sedation subscale (BAES; Martin et al., 1993), measuring sedation effects of alcohol. The seven items included on the sedation subscale range from 1 (not at all) to extremely (10) with higher measurements indicating higher sedation. Assessed multiple times, starting at 50 minutes after priming drink until 230 minutes after priming drink. Area Under the Curve was used to calculate the final score reported for the BAES. As a single summary measure, AUC, was calculated for BAES outcomes based on scores recorded at numerous time points throughout the adlib drinking session The calculation was based on the trapezoidal methods using times 50, 90, 110, 150, 170, 210, and 230 . Based on the distribution, each AUC was log-transformed. Higher AUC levels correspond to greater levels of sedation. | 50-230 minutes after the priming drink during lab session | 
| Craving AUC: Priming Dose Phase | Craving for alcohol based on Alcohol Urge Questionnaire (AUQ, Bohn et al., 1995), which is an 8 item measurement of self-reported alcohol urges that has been shown to be strongly related to alcohol dependence severity. Each item is scored from 1 (strongly disagree) to 7 (strongly agree), with a higher score indicating higher craving. Craving for alcohol based on Alcohol Urge Questionnaire is calculated using Area Under the Curve (AUC). A single summary measure, AUC was calculated for AUQ outcomes based on scores recorded at numerous time points throughout the priming drink session. The calculation was based on the trapezoidal methods using times -20, 10, 20, 30, 40, 50 minutes before/after priming drink. Based on the distribution, each AUC was log-transformed. Higher AUC levels correspond to greater alcohol urge. | 0-50 minutes after the priming drink | 
| Sedation Response to Alcohol: Priming Dose Phase | Brief Biphasic Alcohol Effects Scale-Sedation subscale, measuring sedation effects of alcohol with higher measurements indicating higher sedation. Brief Biphasic Alcohol Effects Scale-Stimulation subscale (BAES; Martin et al., 1993), measuring stimulation effects of alcohol. Seven items ranging from 0 (not at all) to extremely (10) with higher measurements indicating higher stimulation. The subscale total range is 0-70, these scores are logged transformed. | 0-50 minutes after priming drink | 
| Stimulation Response to Alcohol: Priming Dose Phase | Brief Biphasic Alcohol Effects Scale-Stimulation subscale, measuring stimulation effects of alcohol with higher measurements indicating higher stimulation. Brief Biphasic Alcohol Effects Scale-Stimulation subscale (BAES; Martin et al., 1993), measuring stimulation effects of alcohol. Seven items ranging from 0 (not at all) to extremely (10) with higher measurements indicating higher stimulation. The subscale total range is 0-70, these scores are logged transformed. | 0-50 minutes after priming drink | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Alcohol, Drinking, Drinkers, Alcohol Drinking, Memantine, Naltrexone, Alcohol Dependence, Alcohol Abuse, Alcohol-Related Disorders, Ethanol, Alcoholism