Alcohol Abuse, Alcohol Dependence
Conditions
Keywords
Alcohol, Alcoholics, Substance Abuse, Alcohol Abuse, Alcohol Addiction
Brief summary
Purpose: The proposed 2-year investigation will be the first double-blind, placebo-controlled trial examining the hedonic response to sweet taste (HRST) as a phenotypic predictor of naltrexone (NTX) response in alcohol dependence. HRST yields two primary phenotypes-Sweet Likers (SL) and Sweet Dislikers (SDL). Based on preliminary findings, HRST will be examined in conjunction with craving for alcohol to assess whether the two factors together provide a more robust predictor of NTX response. The identification of methods to predict naltrexone response in alcohol dependence is an important goal for alcohol treatment research. Currently naltrexone is not being used nearly as much as it should be, in part because clinicians do not believe it is very effective. The development of tools that would identify which patients are more likely to have a robust response to naltrexone should lead to increased use of the medication. This could help many patients who are not now having the opportunity of trying naltrexone. There are two principal Specific Aims for the study: Specific Aim 1. To test the hypothesis that a combination of SL/SDL status and initial alcohol craving will predict % abstinent days (%ABST) during treatment with naltrexone. Specific Aim 2. To test whether a combination of SL/SDL status and initial alcohol craving predict % heavy drinking days (%HDD) during treatment with naltrexone.
Detailed description
Participants: There will be 130 alcohol-dependent individuals between 18 and 65 years of age recruited to participate in this randomized placebo-controlled clinical trial. Eighty alcohol-dependent individuals will be randomized into the study and we are allowing for 50 screen failures. Participation in this study will be an alternative to standard treatment. Subjects will be blindly assessed for SL/SDL status to yield 50% representation of each trait. Procedures (methods): Subjects who meet general inclusion/exclusion criteria based on the screening interview will complete a sweet taste assessment. Results, along with craving score, will be given to the Investigational Drug Services for randomization purposes. The study is a double-blind, randomized, placebo-controlled clinical trial in which participants will receive 50 mg oral naltrexone or matching placebo for a 12-week period. In addition participants will meet with a trained therapist for nine 30-minute BRENDA therapy sessions Medical monitoring will also be conducted by study physicians and will consist of review of vital signs, concomitant medication use, and general inquiries into side effects.
Interventions
DRUGNaltrexone
50 mg oral naltrexone once/day
BEHAVIORALBrenda Therapy Sessions
participants will meet with a trained therapist for nine 30-minute BRENDA therapy sessions Medical monitoring will also be conducted by study physicians and will consist of review of vital signs, concomitant medication use, and general inquiries into side effects.
DRUGPlacebo
An inactive pill to control for non-pharmacological responses.
Sponsors
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
National Institutes of Health (NIH)
University of North Carolina, Chapel Hill
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Men and women between the ages of 18 and 65 meeting DSM-IV criteria for current alcohol dependence. 2. More than 14 drinks (women) or 21 drinks (men) per week including at least 2 heavy drinking days/week on average (men \> 5 drinks/day; women \> 4 drinks/day) during a consecutive 30-day period within the 90 days prior to screening. 3. Ability to understand and sign written informed consent. 4. Must have a 0.0 gms/dL breathalyzer reading on the day of screening and 0.0 gms/dL on the day of randomization. 5. Must be willing to refrain from drinking for three days prior to randomization day. 6. Express a desire to achieve abstinence or to greatly reduce alcohol consumption. 7. Must have a stable residence and be able to identify an individual who could locate subject if needed.
Exclusion criteria
1. Clinically significant medical disease that might interfere with the evaluation of the study medication or present a safety concern (e.g., cirrhosis, unstable hypertension, seizure disorder, use of opiate medication). 2. Clinically significant psychiatric illness including: any psychotic disorder, bipolar disorder, severe depression, or suicidal ideation. 3. Other substance abuse or dependence disorder other than nicotine or alcohol. 4. Concurrent use of any psychotropic medication including antidepressants, mood stabilizers, antipsychotics, anxiolytics, stimulants, or hypnotics with the exception of stable doses of antidepressants for one month. 5. History of complicated alcohol withdrawal, i.e. withdrawal seizure or delirium tremens. 6. AST, or ALT \> 3 times Upper Limit of Normal (ULN) or bilirubin \> ULN. 7. Positive urine toxicology screen with the exception of cannabis. Individuals with positive cannabis screens will be excluded only if they have a history of cannabis dependence. 8. Pregnant women and women of childbearing potential who do not practice a medically acceptable form of birth control (oral or depot contraceptive, or barrier methods such as diaphragm or condom with spermicidal) and women who are breast feeding. 9. Individuals requiring inpatient treatment or more intense outpatient treatment for their alcohol dependence. 10. Participation in any clinical trial within the past 60 days. 11. Court-mandated participation in alcohol treatment or pending incarceration.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Heavy Drinking Days | 12 weeks | Percentage of heavy drinking days as derived from the Timeline Follow-back (TLFB) for the entire medication period. A heavy drinking day is defined as 5 or more standard drinks for a man and 4 or more standard drinks for a woman. A standard drink is 12-14 grams of ethanol or the amount contained in a 12 oz beer, 5 oz of wine or 1 1/2 oz of hard liquor. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Days Abstinent | 12 weeks | Percentage of abstinence days as derived from the Timeline Follow-Back (TLFB) for the entire medication period. |
Countries
United States
Participant flow
Recruitment details
Recruitment occured primarily via community advertising by radio.
Pre-assignment details
Subjects were screened and, if met criteria, randomized to placebo or naltrexone generally within 5-10 days.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo taken once daily. | 40 |
| Naltrexone 50 mg of naltrexone orally daily. | 40 |
| Total | 80 |
Baseline characteristics
| Characteristic | Placebo | Naltrexone | Total |
|---|---|---|---|
| Age Continuous | 48.3 years STANDARD_DEVIATION 8.4 | 45.8 years STANDARD_DEVIATION 8.6 | 47.0 years STANDARD_DEVIATION 8.5 |
| Region of Enrollment United States | 40 participants | 40 participants | 80 participants |
| Sex: Female, Male Female | 12 Participants | 11 Participants | 23 Participants |
| Sex: Female, Male Male | 28 Participants | 29 Participants | 57 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 2 / 40 | 3 / 40 |
| serious Total, serious adverse events | 1 / 40 | 0 / 40 |
Outcome results
Primary
Percent Heavy Drinking Days
Percentage of heavy drinking days as derived from the Timeline Follow-back (TLFB) for the entire medication period. A heavy drinking day is defined as 5 or more standard drinks for a man and 4 or more standard drinks for a woman. A standard drink is 12-14 grams of ethanol or the amount contained in a 12 oz beer, 5 oz of wine or 1 1/2 oz of hard liquor.
Time frame: 12 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Percent Heavy Drinking Days | Sweet Liker - High Craving n=9 | 0.63 percentage of days | Standard Deviation 0.18 |
| Placebo | Percent Heavy Drinking Days | Sweet Liker - Low Craving n=13 | 0.09 percentage of days | Standard Deviation 0.12 |
| Placebo | Percent Heavy Drinking Days | Sweet Disliker - High Craving n=31 | 0.19 percentage of days | Standard Deviation 0.23 |
| Placebo | Percent Heavy Drinking Days | Sweet Disliker - Low Craving n=27 | 0.12 percentage of days | Standard Deviation 0.22 |
| Naltrexone | Percent Heavy Drinking Days | Sweet Disliker - Low Craving n=27 | 0.14 percentage of days | Standard Deviation 0.27 |
| Naltrexone | Percent Heavy Drinking Days | Sweet Liker - High Craving n=9 | 0.14 percentage of days | Standard Deviation 0.13 |
| Naltrexone | Percent Heavy Drinking Days | Sweet Disliker - High Craving n=31 | 0.16 percentage of days | Standard Deviation 0.2 |
| Naltrexone | Percent Heavy Drinking Days | Sweet Liker - Low Craving n=13 | 0.17 percentage of days | Standard Deviation 0.3 |
Secondary
Percent Days Abstinent
Percentage of abstinence days as derived from the Timeline Follow-Back (TLFB) for the entire medication period.
Time frame: 12 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Percent Days Abstinent | Sweet Disliker - Low Craving n=27 | 0.61 percentage of days | Standard Deviation 0.34 |
| Placebo | Percent Days Abstinent | Sweet Liker - Low Craving n=13 | 0.72 percentage of days | Standard Deviation 0.16 |
| Placebo | Percent Days Abstinent | Sweet Disliker - High Craving n=31 | 0.64 percentage of days | Standard Deviation 0.27 |
| Placebo | Percent Days Abstinent | Sweet Liker - High Craving n=9 | 0.27 percentage of days | Standard Deviation 0.2 |
| Naltrexone | Percent Days Abstinent | Sweet Disliker - Low Craving n=27 | 0.66 percentage of days | Standard Deviation 0.27 |
| Naltrexone | Percent Days Abstinent | Sweet Liker - High Craving n=9 | 0.77 percentage of days | Standard Deviation 0.29 |
| Naltrexone | Percent Days Abstinent | Sweet Disliker - High Craving n=31 | 0.62 percentage of days | Standard Deviation 0.34 |
| Naltrexone | Percent Days Abstinent | Sweet Liker - Low Craving n=13 | 0.67 percentage of days | Standard Deviation 0.29 |