Alcohol Drinking
Conditions
Keywords
Alcohol, Drinking, Drinkers, Alcohol Drinking, Naltrexone, Alcohol Dependence, Alcohol Abuse, Alcohol-Related Disorders, Ethanol, Alcoholism
Brief summary
The primary purpose of the study is to increase our knowledge of receptor function in the brains of people who are heavy drinkers and taking naltrexone (NTX), a medication that has been approved for the treatment of alcohol dependence. Receptors are special molecules in the brain to which other molecules (neurotransmitters) attach during the normal every-day workings of the brain. Drugs can bind to those receptor molecules as well. Recent evidence suggests that kappa opioid receptors (KOR's) may play an important role in alcohol drinking behavior. This study will try to determine if naltrexone's ability to attach to these receptors is related to its effectiveness. We will use PET (positron emission tomography) for this study. PET is a type of imaging device found in nuclear medicine. It is used for tracking the presence of injected radioactive materials in the body.
Interventions
DRUGNaltrexone
Naltrexone 100 mg titrated over one week
Sponsors
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Yale University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
21 Years to 50 Years
Healthy volunteers
No
Inclusion criteria
* Ages 21-50 * 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 |
|---|---|---|
| Occupancy of KOR by NTX and Drinking | 6-8 days after treatment with naltrexone | To determine the degree to which occupancy of KORs by a 100 mg/day dose of NTX mediates (influences the strength of) responsivity to NTX treatment in all heavy drinkers. |
| Relationship Between NTX Responsivity and Occupancy of KOR | 6-8 days after treatment with naltrexone | To determine whether the relationship between NTX responsivity and occupancy of KOR is different in family history positive vs. family history negative heavy drinkers. Evaluations were done with a logistic regression which included years of drinking (a covariate), family history status, and occupancy of KOR. The logistic model calculated a probability of response, defined as a 50% or greater reduction in drinking after naltrexone, for every participant. Reported outcome is the area under the ROC produced by the model. The closer the value is to 100 percent probability, the better the model is at correctly classifying the observations. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Baseline KOR Differences | at baseline prior to treatment with naltrexone | To determine if baseline levels of KOR differ between family history positive (FHP) and family history negative (FHN) heavy drinkers and to determine if baseline KOR level is related to either baseline drinking or responsivity to NTX. |
Countries
United States
Participant flow
Recruitment details
Participants were recruited from the community through various methods such as flyers and online.
Pre-assignment details
All enrolled participants were assigned to a study arm.
Participants by arm
| Arm | Count |
|---|---|
| Naltrexone Naltrexone: Naltrexone 100 mg titrated over one week | 47 |
| Healthy Controls No treatment, baseline measurements only. | 4 |
| Total | 51 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | No adlib drinks Lab 1 | 3 | 0 |
| Overall Study | Technical issues with PET | 1 | 0 |
| Overall Study | Unable to complete study procedures | 1 | 0 |
| Overall Study | Withdrawal by Subject | 3 | 0 |
Baseline characteristics
| Characteristic | Naltrexone | Total | Healthy Controls |
|---|---|---|---|
| Age, Continuous | 32 years STANDARD_DEVIATION 3.9 | 33.8 years STANDARD_DEVIATION 7.7 | 35.6 years STANDARD_DEVIATION 11.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 8 Participants | 8 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 39 Participants | 43 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 22 Participants | 22 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 24 Participants | 28 Participants | 4 Participants |
| Region of Enrollment United States | 47 participants | 51 participants | 4 participants |
| Sex: Female, Male Female | 16 Participants | 19 Participants | 3 Participants |
| Sex: Female, Male Male | 31 Participants | 32 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 55 | 0 / 4 |
| other Total, other adverse events | 37 / 55 | 0 / 4 |
| serious Total, serious adverse events | 0 / 55 | 0 / 4 |
Outcome results
Primary
Occupancy of KOR by NTX and Drinking
To determine the degree to which occupancy of KORs by a 100 mg/day dose of NTX mediates (influences the strength of) responsivity to NTX treatment in all heavy drinkers.
Time frame: 6-8 days after treatment with naltrexone
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Naltrexone | Occupancy of KOR by NTX and Drinking | 92 % Occupancy | Standard Error 1 |
Primary
Relationship Between NTX Responsivity and Occupancy of KOR
To determine whether the relationship between NTX responsivity and occupancy of KOR is different in family history positive vs. family history negative heavy drinkers. Evaluations were done with a logistic regression which included years of drinking (a covariate), family history status, and occupancy of KOR. The logistic model calculated a probability of response, defined as a 50% or greater reduction in drinking after naltrexone, for every participant. Reported outcome is the area under the ROC produced by the model. The closer the value is to 100 percent probability, the better the model is at correctly classifying the observations.
Time frame: 6-8 days after treatment with naltrexone
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Naltrexone | Relationship Between NTX Responsivity and Occupancy of KOR | 84 percent probability |
Secondary
Baseline KOR Differences
To determine if baseline levels of KOR differ between family history positive (FHP) and family history negative (FHN) heavy drinkers and to determine if baseline KOR level is related to either baseline drinking or responsivity to NTX.
Time frame: at baseline prior to treatment with naltrexone
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Naltrexone | Baseline KOR Differences | 91.2 % Occupancy | Standard Error 1.7 |
| Naltrexone - FH Negative | Baseline KOR Differences | 94.2 % Occupancy | Standard Error 1.9 |