Alcohol Drinking
Conditions
Keywords
Alcohol, Drinking, Drinkers, Alcohol Drinking, Memantine, Naltrexone, Alcohol Dependence, Alcohol Abuse, Alcohol-Related Disorders, Ethanol, Alcoholism
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.
Interventions
DRUGNaltrexone and memantine first
Naltrexone 50mg memantine 20mg
DRUGNaltrexone and Placebo first
Naltrexone 50 mg Placebo
Sponsors
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Yale University
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
21 Years to 55 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Drinks Consumed at Lab Session (Day 7) | Day 7 | Number of drinks consumed during the lab session (Day 7) after taking study medication, ranging from 0-12. |
| Craving AUC: Adlib Drinking Phase | 50-230 minutes after the priming drink during lab session | 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. |
| Stimulation Response to Alcohol at Lab Session | 50-230 minutes after the priming drink during 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. |
| Sedation Response to Alcohol at Lab Session | 50-230 minutes after the priming drink during 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. |
| Craving AUC: Priming Dose Phase | 0-50 minutes after the priming drink | 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. |
| Sedation Response to Alcohol: Priming Dose Phase | 0-50 minutes after priming drink | 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. |
| Stimulation Response to Alcohol: Priming Dose Phase | 0-50 minutes after priming drink | 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. |
Countries
United States
Participant flow
Pre-assignment details
The number of participants enrolled was 75. However, 19 people did not start medication due to ineligibility or drop out, leaving 56 total participants.
Participants by arm
| Arm | Count |
|---|---|
| Naltrexone and Memantine First Patients in this arm received Naltrexone and Memantine first. | 26 |
| Naltrexone and Placebo First Patients in this arm received Naltrexone and Placebo first. | 30 |
| Total | 56 |
Baseline characteristics
| Characteristic | Naltrexone and Placebo First | Total | Naltrexone and Memantine First |
|---|---|---|---|
| Age, Continuous | 33 years STANDARD_DEVIATION 9.3 | 33 years STANDARD_DEVIATION 8.9 | 34 years STANDARD_DEVIATION 8.5 |
| Drinks per drinking day in past 90 days | 7.2 drinks STANDARD_DEVIATION 2.9 | 7.2 drinks STANDARD_DEVIATION 2.7 | 7.2 drinks STANDARD_DEVIATION 2.5 |
| Percent of drinking days over past 90 days | 75 percent of days STANDARD_DEVIATION 17 | 76 percent of days STANDARD_DEVIATION 16 | 78 percent of days STANDARD_DEVIATION 16 |
| Race/Ethnicity, Customized Caucasian | 20 Participants | 36 Participants | 16 Participants |
| Race/Ethnicity, Customized Non-Caucasian | 10 Participants | 20 Participants | 10 Participants |
| Sex: Female, Male Female | 12 Participants | 23 Participants | 11 Participants |
| Sex: Female, Male Male | 18 Participants | 33 Participants | 15 Participants |
| Total number of drinks over past 90 days | 165 drinks STANDARD_DEVIATION 1 | 165 drinks STANDARD_DEVIATION 72 | 166 drinks STANDARD_DEVIATION 63 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 47 | 0 / 46 |
| other Total, other adverse events | 3 / 47 | 3 / 46 |
| serious Total, serious adverse events | 0 / 47 | 0 / 46 |
Outcome results
Primary
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.
Time frame: 50-230 minutes after the priming drink during lab session
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Naltrexone and Memantine | Craving AUC: Adlib Drinking Phase | 7.62 log (units on a scale * minutes) | Standard Deviation 0.54 |
| Naltrexone and Placebo | Craving AUC: Adlib Drinking Phase | 7.75 log (units on a scale * minutes) | Standard Deviation 0.55 |
Primary
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.
Time frame: 0-50 minutes after the priming drink
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Naltrexone and Memantine | Craving AUC: Priming Dose Phase | 6.81 log (units on a scale *minutes) | Standard Deviation 0.55 |
| Naltrexone and Placebo | Craving AUC: Priming Dose Phase | 6.84 log (units on a scale *minutes) | Standard Deviation 0.57 |
Primary
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.
Time frame: Day 7
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Naltrexone and Memantine | Number of Drinks Consumed at Lab Session (Day 7) | 4.11 drinks | Standard Deviation 4.19 |
| Naltrexone and Placebo | Number of Drinks Consumed at Lab Session (Day 7) | 5.02 drinks | Standard Deviation 4.32 |
Primary
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.
Time frame: 50-230 minutes after the priming drink during lab session
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Naltrexone and Memantine | Sedation Response to Alcohol at Lab Session | 5.42 log (units on a scale *minutes) | Standard Deviation 2.97 |
| Naltrexone and Placebo | Sedation Response to Alcohol at Lab Session | 5.34 log (units on a scale *minutes) | Standard Deviation 3.08 |
Primary
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.
Time frame: 0-50 minutes after priming drink
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Naltrexone and Memantine | Sedation Response to Alcohol: Priming Dose Phase | 3.87 log (units on a scale) | Standard Deviation 2.49 |
| Naltrexone and Placebo | Sedation Response to Alcohol: Priming Dose Phase | 3.76 log (units on a scale) | Standard Deviation 2.34 |
Primary
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.
Time frame: 50-230 minutes after the priming drink during lab session
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Naltrexone and Memantine | Stimulation Response to Alcohol at Lab Session | 4.78 log (units on a scale *minutes) | Standard Deviation 3.51 |
| Naltrexone and Placebo | Stimulation Response to Alcohol at Lab Session | 4.93 log (units on a scale *minutes) | Standard Deviation 3.45 |
Primary
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.
Time frame: 0-50 minutes after priming drink
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Naltrexone and Memantine | Stimulation Response to Alcohol: Priming Dose Phase | 3.20 log (units on a scale) | Standard Deviation 2.84 |
| Naltrexone and Placebo | Stimulation Response to Alcohol: Priming Dose Phase | 3.43 log (units on a scale) | Standard Deviation 2.71 |