Substance Dependence
Conditions
Brief summary
Purpose: This is an outpatient, randomized, double-blinded, placebo-controlled study in which either varenicline (twice daily) or placebo will be administered over a 12 week study period to examine genetic influences on treatment response to varenicline for reduction of hazardous drinking.
Detailed description
Hazardous alcohol use and alcohol use disorders (AUDs) are an area of large unmet medical needs. Although there has been some progress with pharmacotherapy for alcohol-dependent individuals, a critical need for the development of novel and additional therapeutic approaches remains. Pharmacotherapy development for AUDs as a therapeutic area has had several recent advancements, where clinically as well as commercially successful additions to available treatment options are available and several more are expected in the near future. Based on recent preclinical work, we believe that varenicline has potential to become one of the first among those newly evolving treatments. In this study, participants with nicotine dependence will receive standard varenicline or placebo treatment over the recommended course of 12 weeks. Since our research question addresses whether alcohol drinking also diminishes with varenicline treatment, we will not ask participants to alter alcohol use; we will simply follow their use over time. Study visits will take place at the Ernest Gallo Clinic and Research Center. The procedures to be completed include vital signs, blood samples at screening and end of study, urine toxicology screening and the completion of standard questionnaires. No special facilities are required for these procedures. Group therapy (which is not a research procedure, but part of standard nicotine dependence treatment) will take place at the Gallo Center.
Interventions
DRUGvarenicline
12 weeks of oral tablet treatment in an escalating dosing regimen (0.5 mg 1x daily, days 1-3; 0.5mg 2x daily, days 4-7, 1.0 mg 2x daily, days 8-84).
DRUGplacebo
12 weeks of oral tablet treatment in an escalating dosing regimen (1 - 2x daily).
Sponsors
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
University of California, San Francisco
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
21 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Age between 21 and 75 years. * Currently seeking treatment for nicotine dependence (smoke at least 10 cigarettes daily) and found to have problem drinking, alcohol abuse or alcohol dependence (non-physiological) as determined by amount of alcohol consumed weekly (Average weekly alcohol consumption (last 30 days), \>7 standard drinks (for women) or \>14 standard drinks (for men), clinical interview, and AUDIT score \> 8. * Generally healthy, without serious or unstable medical/mental illness(es). * Smokers only will be included (degree of nicotine dependence will be assessed and included in analysis). * Able to give voluntary, written, informed consent
Exclusion criteria
* More than 30 days of abstinence from alcohol in the prior 90 days. * History of major alcohol-related complications within the preceding 2 years (liver failure/cirrhosis, pancreatitis, esophageal varices, liver function tests \> 3 X ULN). * Intolerance to the study medication. * Current psychiatric disorder(s) requiring clinical treatment. * Any recent history (i.e. within the preceding 5 years) of suicide attempt or current suicidal ideation. * Use of illicit or non-prescribed psychotropic drug use (opiates, benzodiazepines, cocaine, PCP, methamphetamine, cocaine, or marijuana more than twice a week). * A history of complicated alcohol or other drug withdrawal syndrome(s), e.g.: delirium tremens or seizures.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Average Number of Cigarettes Smoked Between the Varenicline and Placebo Groups for Completers Through Week 12. | Weeks 1-12 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Average Number of Alcoholic Drinks Consumed Between the Varenicline and Placebo Groups for Completers of the Study Through Week 12. | Weeks 1-12 | — |
| Alcohol Craving as Measured by the Obsessive Compulsive Drinking Scale (OCDS) Between Varenicline and Placebo Groups for Completers of the Study. | Week 1 to Week 12 | Higher scores on the OCDS indicate increased craving. OCDS possible score range = 0 - 40. Difference in average OCDS scores from week 1 to week 12 were reported for the varenicline and placebo groups in subjects that completed the study. |
Countries
United States
Participant flow
Pre-assignment details
99 subjects were consented of which 64 successfully completed the screening process were randomized to treatment. Results are posted for the 35 subjects who completed the study.
Participants by arm
| Arm | Count |
|---|---|
| Placebo | 17 |
| Varenicline | 18 |
| Total | 35 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 4 |
| Overall Study | Withdrawal by Subject | 13 | 11 |
Baseline characteristics
| Characteristic | Placebo | Varenicline | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 17 Participants | 18 Participants | 35 Participants |
| Region of Enrollment United States | 17 participants | 18 participants | 35 participants |
| Sex: Female, Male Female | 8 Participants | 9 Participants | 17 Participants |
| Sex: Female, Male Male | 9 Participants | 9 Participants | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 31 | 0 / 33 |
| serious Total, serious adverse events | 1 / 31 | 0 / 33 |
Outcome results
Primary
Average Number of Cigarettes Smoked Between the Varenicline and Placebo Groups for Completers Through Week 12.
Time frame: Weeks 1-12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Average Number of Cigarettes Smoked Between the Varenicline and Placebo Groups for Completers Through Week 12. | 788.94 cigarettes | Standard Error 96.27 |
| Varenicline | Average Number of Cigarettes Smoked Between the Varenicline and Placebo Groups for Completers Through Week 12. | 403.24 cigarettes | Standard Error 102.42 |
Secondary
Alcohol Craving as Measured by the Obsessive Compulsive Drinking Scale (OCDS) Between Varenicline and Placebo Groups for Completers of the Study.
Higher scores on the OCDS indicate increased craving. OCDS possible score range = 0 - 40. Difference in average OCDS scores from week 1 to week 12 were reported for the varenicline and placebo groups in subjects that completed the study.
Time frame: Week 1 to Week 12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Alcohol Craving as Measured by the Obsessive Compulsive Drinking Scale (OCDS) Between Varenicline and Placebo Groups for Completers of the Study. | -3.07 Scores on a scale | Standard Error 0.389 |
| Varenicline | Alcohol Craving as Measured by the Obsessive Compulsive Drinking Scale (OCDS) Between Varenicline and Placebo Groups for Completers of the Study. | -4.36 Scores on a scale | Standard Error 0.205 |
Secondary
Average Number of Alcoholic Drinks Consumed Between the Varenicline and Placebo Groups for Completers of the Study Through Week 12.
Time frame: Weeks 1-12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Average Number of Alcoholic Drinks Consumed Between the Varenicline and Placebo Groups for Completers of the Study Through Week 12. | 277.5 drinks | Standard Error 41.9 |
| Varenicline | Average Number of Alcoholic Drinks Consumed Between the Varenicline and Placebo Groups for Completers of the Study Through Week 12. | 177.04 drinks | Standard Error 28.86 |