Alcohol Dependence
Conditions
Keywords
Alcohol, Alcohol treatment, Alcoholism, Alcohol Abuse, Alcohol Dependence
Brief summary
A 12-week, double-blind, placebo-controlled parallel group study will be conducted with 150 outpatients with alcohol dependence, with random assignment to pregabalin 300 mg/d, duloxetine 40 mg/d, or placebo in conjunction with manual-guided behavioral counseling and follow-up visits 1 week and 3 months post-treatment.
Interventions
DRUGPregabalin
Two 150 mg capsules, 150 mg/am and 150 mg/pm (Total dose, 300mg/d), 12 week duration. Dose may be increased up to 600 mg/d or reduced to 150 mg/d based on subject response and tolerability.
DRUGDuloxetine
40 mg capsule, Once daily/am, 12 week duration, placebo capsule administered pm. Dose may be increased up to 60 mg/d or reduced to 20 mg/d based on subject response and tolerability.
BEHAVIORALStandardized behavioral therapy
Standardized behavioral therapy 1 time per week for 12 week duration.
DRUGPlacebo
Matched placebo capsule administered 1 capsule am and 1 capsule pm for 12 week duration.
Sponsors
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
The Scripps Research Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Males or females 18 years of age * Meets DSM-IV criteria for current alcohol dependence and drinking an average of ≥21 drinks weekly for males, ≥14 females, * Seeking research-based outpatient treatment for alcohol problems * Willing to attend 12 weekly study visits and 2 follow-up visits * Have normal bilirubin, and ALT, AST, and GGT values no more than 3x the ULN, and no evidence of hepatic insufficiency
Exclusion criteria
* Active suicidal ideation * Medical disorders that will increase potential risk or interfere with study participation * Sexually active female subjects with childbearing potential who are pregnant, nursing or refuse to use a reliable method of birth control * Males who refuse to use a reliable method of birth control * Meets DSM-IV criteria for any other current major AXIS I disorder other than alcohol or nicotine dependence. * Inability to understand and/or comply with the provisions of the protocol and consent form * Treatment with an antidepressant medication during the two weeks, or fluoxetine during the month, prior to randomization * Ongoing treatment with disulfiram (Antabuse), naltrexone (ReVia), acamprosate (Campral) or other medications that may affect study outcomes, e.g., anticonvulsants or other drugs that act on serotonin in the brain * Ongoing treatment with drugs that may increase potential risk (Actos),
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Drinking Quantity and Frequency Using Drinks Per Week at Week 12 | Baseline and Week 12 | Standard drinks are equivalent to 14 grams of pure alcohol and number of drinks are assessed with Timeline Follow-Back (TLFB) methods. Change = (Week 12 - Baseline). More negative values indicate less use of alcohol. |
| Change From Baseline in Drinking Quantity and Frequency Using Drinking Days Per Week at Week 12 | Baseline and Week 12 | Standard drinks are equivalent to 14 grams of pure alcohol and number of drinks are assessed with Timeline Follow-Back (TLFB) methods. A drinking day is a day where any alcohol is consumed. Change = (Week 12 - Baseline). More negative values indicate less use of alcohol. |
| Change From Baseline in Drinking Quantity and Frequency Using Drinks Per Drinking Day at Week 12 | Baseline and Week 12 | Standard drinks are equivalent to 14 grams of pure alcohol and number of drinks are assessed with Timeline Follow-Back (TLFB) methods. A drinking day is a day where any alcohol is consumed. Change = (Week 12 - Baseline). More negative values indicate less use of alcohol. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Duloxetine Duloxetine: 40 mg capsule, Once daily/am, 12 week duration, placebo capsule administered pm. Dose may be increased up to 60 mg/d or reduced to 20 mg/d based on subject response and tolerability.
Standardized behavioral therapy: Standardized behavioral therapy 1 time per week for 12 week duration. | 50 |
| Pregabalin Pregabalin: Two 150 mg capsules, 150 mg/am and 150 mg/pm (Total dose, 300mg/d), 12 week duration. Dose may be increased up to 600 mg/d or reduced to 150 mg/d based on subject response and tolerability.
Standardized behavioral therapy: Standardized behavioral therapy 1 time per week for 12 week duration. | 50 |
| Placebo Placebo: Matched placebo capsule administered 1 capsule am and 1 capsule pm for 12 week duration.
Standardized behavioral therapy: Standardized behavioral therapy 1 time per week for 12 week duration. | 50 |
| Total | 150 |
Baseline characteristics
| Characteristic | Duloxetine | Pregabalin | Placebo | Total |
|---|---|---|---|---|
| Age, Continuous | 44.86 years STANDARD_DEVIATION 10.53 | 44.56 years STANDARD_DEVIATION 11.55 | 43.54 years STANDARD_DEVIATION 10.52 | 44.32 years STANDARD_DEVIATION 10.82 |
| Sex: Female, Male Female | 19 Participants | 13 Participants | 23 Participants | 55 Participants |
| Sex: Female, Male Male | 31 Participants | 37 Participants | 27 Participants | 95 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 | 43 / 50 | 35 / 50 | 33 / 50 |
| serious Total, serious adverse events | 2 / 50 | 0 / 50 | 4 / 50 |
Outcome results
Primary
Change From Baseline in Drinking Quantity and Frequency Using Drinking Days Per Week at Week 12
Standard drinks are equivalent to 14 grams of pure alcohol and number of drinks are assessed with Timeline Follow-Back (TLFB) methods. A drinking day is a day where any alcohol is consumed. Change = (Week 12 - Baseline). More negative values indicate less use of alcohol.
Time frame: Baseline and Week 12
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Duloxetine | Change From Baseline in Drinking Quantity and Frequency Using Drinking Days Per Week at Week 12 | Drinking Days/Week Week 12 | 2.17 drinking days/week | Standard Deviation 2.59 |
| Duloxetine | Change From Baseline in Drinking Quantity and Frequency Using Drinking Days Per Week at Week 12 | Drinking Days/Week Baseline | 5.11 drinking days/week | Standard Deviation 1.29 |
| Duloxetine | Change From Baseline in Drinking Quantity and Frequency Using Drinking Days Per Week at Week 12 | Drinking Days/Week Change | -2.94 drinking days/week | Standard Deviation 2.68 |
| Pregabalin | Change From Baseline in Drinking Quantity and Frequency Using Drinking Days Per Week at Week 12 | Drinking Days/Week Week 12 | 1.14 drinking days/week | Standard Deviation 1.9 |
| Pregabalin | Change From Baseline in Drinking Quantity and Frequency Using Drinking Days Per Week at Week 12 | Drinking Days/Week Baseline | 4.54 drinking days/week | Standard Deviation 1.64 |
| Pregabalin | Change From Baseline in Drinking Quantity and Frequency Using Drinking Days Per Week at Week 12 | Drinking Days/Week Change | -3.40 drinking days/week | Standard Deviation 2.03 |
| Placebo | Change From Baseline in Drinking Quantity and Frequency Using Drinking Days Per Week at Week 12 | Drinking Days/Week Baseline | 4.87 drinking days/week | Standard Deviation 1.6 |
| Placebo | Change From Baseline in Drinking Quantity and Frequency Using Drinking Days Per Week at Week 12 | Drinking Days/Week Change | -3.01 drinking days/week | Standard Deviation 2.2 |
| Placebo | Change From Baseline in Drinking Quantity and Frequency Using Drinking Days Per Week at Week 12 | Drinking Days/Week Week 12 | 1.85 drinking days/week | Standard Deviation 2.2 |
Primary
Change From Baseline in Drinking Quantity and Frequency Using Drinks Per Drinking Day at Week 12
Standard drinks are equivalent to 14 grams of pure alcohol and number of drinks are assessed with Timeline Follow-Back (TLFB) methods. A drinking day is a day where any alcohol is consumed. Change = (Week 12 - Baseline). More negative values indicate less use of alcohol.
Time frame: Baseline and Week 12
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Duloxetine | Change From Baseline in Drinking Quantity and Frequency Using Drinks Per Drinking Day at Week 12 | Drinks/Drinking Day Change | -5.94 drinks/drinking day | Standard Deviation 3.54 |
| Duloxetine | Change From Baseline in Drinking Quantity and Frequency Using Drinks Per Drinking Day at Week 12 | Drinks/Drinking Day Week 12 | 2.21 drinks/drinking day | Standard Deviation 2.65 |
| Duloxetine | Change From Baseline in Drinking Quantity and Frequency Using Drinks Per Drinking Day at Week 12 | Drinks/Drinking Day Baseline | 8.16 drinks/drinking day | Standard Deviation 2.69 |
| Pregabalin | Change From Baseline in Drinking Quantity and Frequency Using Drinks Per Drinking Day at Week 12 | Drinks/Drinking Day Change | -10.67 drinks/drinking day | Standard Deviation 11.34 |
| Pregabalin | Change From Baseline in Drinking Quantity and Frequency Using Drinks Per Drinking Day at Week 12 | Drinks/Drinking Day Baseline | 12.98 drinks/drinking day | Standard Deviation 11.14 |
| Pregabalin | Change From Baseline in Drinking Quantity and Frequency Using Drinks Per Drinking Day at Week 12 | Drinks/Drinking Day Week 12 | 2.31 drinks/drinking day | Standard Deviation 3.81 |
| Placebo | Change From Baseline in Drinking Quantity and Frequency Using Drinks Per Drinking Day at Week 12 | Drinks/Drinking Day Week 12 | 2.90 drinks/drinking day | Standard Deviation 3.62 |
| Placebo | Change From Baseline in Drinking Quantity and Frequency Using Drinks Per Drinking Day at Week 12 | Drinks/Drinking Day Baseline | 8.91 drinks/drinking day | Standard Deviation 5.41 |
| Placebo | Change From Baseline in Drinking Quantity and Frequency Using Drinks Per Drinking Day at Week 12 | Drinks/Drinking Day Change | -6.01 drinks/drinking day | Standard Deviation 4.84 |
Primary
Change From Baseline in Drinking Quantity and Frequency Using Drinks Per Week at Week 12
Standard drinks are equivalent to 14 grams of pure alcohol and number of drinks are assessed with Timeline Follow-Back (TLFB) methods. Change = (Week 12 - Baseline). More negative values indicate less use of alcohol.
Time frame: Baseline and Week 12
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Duloxetine | Change From Baseline in Drinking Quantity and Frequency Using Drinks Per Week at Week 12 | Drinks/week Change | -32.91 drinks/week | Standard Deviation 20.38 |
| Duloxetine | Change From Baseline in Drinking Quantity and Frequency Using Drinks Per Week at Week 12 | Drinks/week Week 12 | 9.16 drinks/week | Standard Deviation 11.9 |
| Duloxetine | Change From Baseline in Drinking Quantity and Frequency Using Drinks Per Week at Week 12 | Drinks/week Baseline | 42.07 drinks/week | Standard Deviation 17.94 |
| Pregabalin | Change From Baseline in Drinking Quantity and Frequency Using Drinks Per Week at Week 12 | Drinks/week Change | -49.08 drinks/week | Standard Deviation 44.91 |
| Pregabalin | Change From Baseline in Drinking Quantity and Frequency Using Drinks Per Week at Week 12 | Drinks/week Baseline | 56.67 drinks/week | Standard Deviation 50.93 |
| Pregabalin | Change From Baseline in Drinking Quantity and Frequency Using Drinks Per Week at Week 12 | Drinks/week Week 12 | 7.59 drinks/week | Standard Deviation 15.73 |
| Placebo | Change From Baseline in Drinking Quantity and Frequency Using Drinks Per Week at Week 12 | Drinks/week Change | -33.15 drinks/week | Standard Deviation 23.32 |
| Placebo | Change From Baseline in Drinking Quantity and Frequency Using Drinks Per Week at Week 12 | Drinks/week Week 12 | 8.06 drinks/week | Standard Deviation 11.22 |
| Placebo | Change From Baseline in Drinking Quantity and Frequency Using Drinks Per Week at Week 12 | Drinks/week Baseline | 41.20 drinks/week | Standard Deviation 27.39 |