Alcohol Dependence
Conditions
Keywords
Alcohol dependence, Alcoholism, Heavy drinking
Brief summary
The purpose of this study is to determine whether, after a period of abstinence, adding 6 weeks of gabapentin (a medication approved to treat seizures) to a standard 16-week naltrexone (an opiate blocking agent approved for the treatment of alcohol dependence) treatment protocol is helpful in decreasing relapse to drinking compared to naltrexone alone or placebo. All participants will receive alcohol counseling.
Detailed description
Subjects will enter the trial after maintaining 4 days of abstinence. During this period multiple assessments will be collected. After entering the double blind treatment portion of the study, they will be evaluated weekly for the first month, then bi-weekly until week 12 and again at week 16. There will be two follow-up visits at weeks 28 and 40. Urinary riboflavin and pill counts will be utilized to determine compliance with the medication regime. Comparison(s): Naltrexone (50 mg/day) alone for 16-weeks; naltrexone (50 mg/day) for 16-weeks plus gabapentin (up to 1200 mg/day in divided doses) for the first 6 weeks, or inactive placebos. All subjects will receive up to 20 sessions of individual alcohol counseling.
Interventions
DRUGNaltrexone
Naltrexone (50 mg/day) plus gabapentin placebo in divided doses for the first 6weeks. Naltrexone (50 mg/day) for rest of 16-weeks
DRUGNaltrexone plus Gabapentin
naltrexone (50 mg/day) for 16-weeks plus gabapentin (up to 1200 mg/day in divided doses) for the first 6 weeks
OTHERInactive Placebo
Placebo
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
* Meet criteria for primary alcohol dependence including loss of control of drinking * No more than one previous inpatient medical detoxification * Consumes on average 5 standard drinks for men and 4 standard drinks for women * Able to maintain sobriety for 4 days (with or without detox medications). * Able to read and understand questionnaires and Informed Consent * Lives within 50 miles of the study site
Exclusion criteria
* Currently meets DSM-IV criteria for any other psychoactive substance dependency disorder except nicotine dependence * Ever abused opiates * Any psychoactive substance abuse, except marijuana and nicotine within the last 30 days as evidenced by subject report, collateral report, or urine drug screen. * Meets DSM-IV criteria for current Axis I disorder of major depression, panic disorder, obsessive-compulsive disorder, post-traumatic stress syndrome, bipolar affective disorder, dissociative disorder or eating disorder, schizophrenia, or any other psychotic disorder or organic mental disorder. * Has current suicidal or homicidal ideation * Need for maintenance or acute treatment with any psychoactive medication including antiseizure medications. * Current use of disulfiram. * Clinically significant medical problems, such as cardiovascular, renal, GI or endocrine problem that would impair participation or limit medication ingestion. * 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 of abstinence. * Sexually active females of child bearing potential who are pregnant (by urine HCG), nursing or who are not using a reliable form of birth control. * Has current charges pending for a violent crime (not including DUI related offenses). * Does not have a stable living situation and a reliable source of collateral reporting. * Has taken an opiate antagonist drug in the last month. * Has taken gabapentin in the last month or has experienced adverse effects from it at any time in the past.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to Relapse to Drinking | 16 weeks | Time to relapse drinking which is 5 standard drinks perday for males and 4 standard drinks per day for females. Subjects had a minimum of 4 days of abstinence prior to being entered into the protocol. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Naltrexone Plus Gabapentin and CBI Naltrexone plus gabapentin and CBI individual counseling for 6 weeks then naltrexone and CBI for 10 additional weeks. | 50 |
| Naltrexone Plus Placebo and CBI Naltrexone plus placebo and CBI individual counseling for 6 weeks then naltrexone and CBI counseling for 10 weeks. | 50 |
| Placebo Plus Placebo Plus CBI Placebo plus placebo for 6 weeks and CBI individual counseling then placebo and CBI counseling for 10 additional weeks. | 50 |
| Total | 150 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 2 | 2 |
| Overall Study | Legal event | 1 | 1 | 1 |
| Overall Study | Required more intensive care | 0 | 1 | 2 |
| Overall Study | Withdrawal by Subject | 18 | 11 | 13 |
Baseline characteristics
| Characteristic | Naltrexone Plus Placebo and CBI | Placebo Plus Placebo Plus CBI | Naltrexone Plus Gabapentin and CBI | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 1 Participants | 0 Participants | 2 Participants |
| Age, Categorical Between 18 and 65 years | 49 Participants | 49 Participants | 50 Participants | 148 Participants |
| Age, Continuous | 44.4 years STANDARD_DEVIATION 10.1 | 46.6 years STANDARD_DEVIATION 9 | 43 years STANDARD_DEVIATION 9.8 | 44.6 years STANDARD_DEVIATION 9.7 |
| Region of Enrollment United States | 50 participants | 50 participants | 50 participants | 150 participants |
| Sex: Female, Male Female | 11 Participants | 10 Participants | 10 Participants | 31 Participants |
| Sex: Female, Male Male | 39 Participants | 40 Participants | 40 Participants | 119 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 39 / 50 | 29 / 50 | 31 / 50 |
| serious Total, serious adverse events | 0 / 50 | 0 / 50 | 0 / 50 |
Outcome results
Primary
Time to Relapse to Drinking
Time to relapse drinking which is 5 standard drinks perday for males and 4 standard drinks per day for females. Subjects had a minimum of 4 days of abstinence prior to being entered into the protocol.
Time frame: 16 weeks
Population: Subjects who entered the analysis were all people with any drinking data post randomization. There was 2 people in naltrexone plus gabapentin, 1 person in naltrexone alone and 1 person in placebo group that had no post-randomization drinking data and were therefore not included in the intent to treat analysis presented.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Naltrexone Plus Gabapentin and CBI | Time to Relapse to Drinking | 69.9 days | Standard Error 6.5 |
| Naltrexone Plus Placebo and CBI | Time to Relapse to Drinking | 59.6 days | Standard Error 7.6 |
| Placebo Plus Placebo Plus CBI | Time to Relapse to Drinking | 57.3 days | Standard Error 6.7 |
95% CI: [0.281, 0.997]Regression, Cox
p-value: 0.04Regression, Cox