Alcohol Dependence
Conditions
Keywords
Alcohol Dependence, Alcoholism, Naltrexone, Aripiprazole, Substance Abuse
Brief summary
The principal aim of this exploratory study is to examine whether the addition of aripiprazole to naltrexone will enhance efficacy over naltrexone alone in a 16-week randomized, placebo-controlled clinical trial, in which all subjects will be provided medical management as delivered in the COMBINE Study (Anton et al, 2006). To test whether medication treatment will reduce drinking compared to placebo treatment alone in the context of medical management and whether naltrexone plus aripiprazole will reduce drinking compared to naltrexone treatment alone in the context of medical management.
Interventions
DRUGPlacebo
placebo
DRUGNaltrexone
Naltrexone (25mg or 50 mg per titration schedule)
DRUGNaltrexone + Aripiprazole
Naltrexone + Aripiprazole (5mg - 15mg per titration schedule)
Sponsors
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Medical University of South Carolina
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 70 Years
Healthy volunteers
No
Inclusion criteria
1. Age 18 70 2. Subjects will meet criteria for primary alcohol dependence operationalized as follows: A. Meets the DSM IV criteria for alcohol dependence including loss of control over drinking (criterion 3) B. Has not had more than one previous inpatient medical detoxification 3. Consumes, on average, at least 10 standard drinks per drinking day for men and 8 drinks per day for women in the 90 days pre-screening (to select an appropriately heavy drinking population) 4. Able to maintain sobriety for four days (with or without the aid of alcohol detoxification medications) as determined by self report, collateral 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 dependency disorder except nicotine dependence 2. Ever abused opiates 3. Any psychoactive substance abuse, except marijuana and nicotine, within the last 30 days as evidenced by subject report, collateral report, or urine drug screen 4. Meets DSM IV criteria for current 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 5. Meets DSM IV current criteria for dissociative disorder or eating disorders 6. Has current suicidal ideation or homicidal ideation 7. Need for maintenance or acute treatment with any psychoactive medication including anti-seizure medications 8. Current use of disulfiram 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 using 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 and a reliable source of collateral reporting 14. Has taken an opiate antagonist drug in the last month 15. Has taken aripiprazole in the last month or has experienced adverse effects from it at any time in the past
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Drinks Per Drinking Day | 16-week treatment period | Standard drinks per drinking day |
| Percent Heavy Drinking Days | 16 weeks | percent of total 112 day trial in which heavy drinking occurred (\>=4 for females, \>=5 male) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pill Counts During Treatment | 16-week | Compliance with medication as determined by pill counts |
| Percent Riboflavin Positive Urine Samples as a Measure of Medication Compliance | 16 weeks treatment trial | Riboflavin was added to each individual capsule of medication and measured as a proxy for compliance with the medication regime |
Countries
United States
Participant flow
Recruitment details
Subjects were recruited from the community in response to advertising in local papers, and radio
Pre-assignment details
Subjects were to remain abstinent for 4 days prior to starting treatment with the randomly assigned study drug.
Participants by arm
| Arm | Count |
|---|---|
| 1 Placebo Placebo : placebo | 23 |
| 2 Naltrexone Naltrexone
Naltrexone : Naltrexone (25mg or 50 mg per titration schedule) | 21 |
| 3 Naltrexone Plus Aripiprazole Naltrexone + Aripiprazole
Naltrexone + Aripiprazole : Naltrexone + Aripiprazole (5mg - 15mg per titration schedule) | 21 |
| Total | 65 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 2 | 6 |
| Overall Study | Withdrawal by Subject | 10 | 9 | 7 |
Baseline characteristics
| Characteristic | 1 Placebo | 2 Naltrexone | 3 Naltrexone Plus Aripiprazole | Total |
|---|---|---|---|---|
| Age, Continuous | 47 years STANDARD_DEVIATION 9.6 | 47.2 years STANDARD_DEVIATION 11.3 | 48.4 years STANDARD_DEVIATION 10.2 | 47.6 years STANDARD_DEVIATION 10.2 |
| Sex: Female, Male Female | 7 Participants | 7 Participants | 9 Participants | 23 Participants |
| Sex: Female, Male Male | 16 Participants | 14 Participants | 12 Participants | 42 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 23 | 0 / 21 | 0 / 21 |
| other Total, other adverse events | 21 / 23 | 20 / 21 | 19 / 21 |
| serious Total, serious adverse events | 0 / 23 | 0 / 21 | 0 / 21 |
Outcome results
Primary
Drinks Per Drinking Day
Standard drinks per drinking day
Time frame: 16-week treatment period
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Inactive Placebo | Drinks Per Drinking Day | 7.2 drinks per drinking day | Standard Deviation 7.3 |
| Naltrexone and Inactive Placebo Aripiprazole | Drinks Per Drinking Day | 7.8 drinks per drinking day | Standard Deviation 6.6 |
| Naltrexone + Aripiprazole | Drinks Per Drinking Day | 5.2 drinks per drinking day | Standard Deviation 7.2 |
Comparison: Analyzed as a mixed model, Group by time (4 time blocks) with an unstructured variance/covariance matrix. Baseline drinks per day was used as a covariate.p-value: 0.49Mixed Models Analysis
Primary
Percent Heavy Drinking Days
percent of total 112 day trial in which heavy drinking occurred (\>=4 for females, \>=5 male)
Time frame: 16 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Inactive Placebo | Percent Heavy Drinking Days | 10.54 percent of days | Standard Deviation 20 |
| Naltrexone and Inactive Placebo Aripiprazole | Percent Heavy Drinking Days | 16.7 percent of days | Standard Deviation 19.9 |
| Naltrexone + Aripiprazole | Percent Heavy Drinking Days | 7.34 percent of days | Standard Deviation 19.7 |
Comparison: Analyzed as a mixed model (SPSS linear mixed) with an unstructured variance/covariance and baseline percent heavy drinking days as a covariatep-value: 0.03Mixed Models Analysis
Secondary
Percent Riboflavin Positive Urine Samples as a Measure of Medication Compliance
Riboflavin was added to each individual capsule of medication and measured as a proxy for compliance with the medication regime
Time frame: 16 weeks treatment trial
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Inactive Placebo | Percent Riboflavin Positive Urine Samples as a Measure of Medication Compliance | 74.9 Percent of riboflavin positive samples | Standard Deviation 33.7 |
| Naltrexone and Inactive Placebo Aripiprazole | Percent Riboflavin Positive Urine Samples as a Measure of Medication Compliance | 85.1 Percent of riboflavin positive samples | Standard Deviation 18.5 |
| Naltrexone + Aripiprazole | Percent Riboflavin Positive Urine Samples as a Measure of Medication Compliance | 62.1 Percent of riboflavin positive samples | Standard Deviation 30.9 |
Comparison: Anova across three groupsp-value: <0.05ANOVA
Secondary
Pill Counts During Treatment
Compliance with medication as determined by pill counts
Time frame: 16-week
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Inactive Placebo | Pill Counts During Treatment | Percent aripiprazole or aripiprazole placebo taken | 96.4 Percent of pills taken | Standard Deviation 6.5 |
| Inactive Placebo | Pill Counts During Treatment | Percent naltrexone or naltrexone placebo taken | 96.8 Percent of pills taken | Standard Deviation 5.9 |
| Naltrexone and Inactive Placebo Aripiprazole | Pill Counts During Treatment | Percent aripiprazole or aripiprazole placebo taken | 97.0 Percent of pills taken | Standard Deviation 4.7 |
| Naltrexone and Inactive Placebo Aripiprazole | Pill Counts During Treatment | Percent naltrexone or naltrexone placebo taken | 96.9 Percent of pills taken | Standard Deviation 4.2 |
| Naltrexone + Aripiprazole | Pill Counts During Treatment | Percent aripiprazole or aripiprazole placebo taken | 84.2 Percent of pills taken | Standard Deviation 25.2 |
| Naltrexone + Aripiprazole | Pill Counts During Treatment | Percent naltrexone or naltrexone placebo taken | 86.4 Percent of pills taken | Standard Deviation 22.7 |
p-value: <0.05ANOVA