Alcohol Abuse, Alcohol Drinking, Alcoholism, Smoking
Conditions
Keywords
alcohol-related disorders, Cholinergic Drugs, varenicline, Chantix
Brief summary
The purpose of this study is to determine whether varenicline is effective in the treatment of alcohol dependence in smokers.
Detailed description
Building upon knowledge about the role of nicotinic acetylcholine receptors in alcohol drinking and smoking, varenicline, a smoking cessation treatment that targets these receptors, will be tested as a potential treatment for alcohol dependent smokers seeking alcohol treatment.
Interventions
DRUGVarenicline
0.5 mg once per day for Days 1 to 3, 0.5 mg twice per day for Days 4 to 7, then two 0.5 mg tablets (1 mg) twice per day
Sponsors
Columbia University
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Yale University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* are 18 - 70 years of age and seeking treatment of alcohol drinking; * meet DSM-IV TR Criteria for Alcohol Dependence * report smoking 100 cigarettes or more in their lifetime and currently smoke at least twice weekly on average in the past 90 days and have a urinary cotinine level of \> 30ng/mL by semi-quantitative urinalysis or equivalent plasma cotinine level (\> 6 ng/mL); * report heavy drinking on at least 2 days on average per week (i.e., ≥ 4 drinks on an occasion for women and ≥ 5 drinks for men) for the past 90 days and no more than 7 consecutive days of abstinence at intake.
Exclusion criteria
* exhibit current, clinically significant physical disease or abnormality based on medical history, physical examination, or routine laboratory evaluation including: * any unexplained elevations in liver enzymes (i.e., transaminases, bilirubin) * clinically significant, unstable cardiovascular disease/uncontrolled hypertension * hepatic or renal impairment * severe obstructive pulmonary disease * diabetes mellitus requiring insulin or certain oral medications (i.e., sulfonylureas) and an A1C hemoglobin test score of \> 7 for participants not prescribed these medications * baseline systolic blood pressure higher than 150 mm Hg or diastolic blood pressure higher than 95 mm Hg * have a history of cancer (except treated basal cell or squamous cell carcinoma of the skin) * have a history of serious hypersensitivity reactions or skin reactions to varenicline; * exhibit serious psychiatric illness (i.e., schizophrenia, bipolar disorder, severe major depression, panic disorder, borderline personality disorder, organic mood or mental disorders by history or psychological examination * report current suicidal ideation (past 6 months) or lifetime hx of suicidal behavior assessed with the Columbia Suicide Severity Rating Scale 60; or risk for aggression using a cut-off of 15 or more on the Overt Aggression Scale - Modified Aggression Scale or 6 or more on the OAS-M Irritability Subscale 61. * have used any psychotropic drug in the past month, except individuals who are on a stable dose of a Selective Serotonin Reuptake Inhibitor for at least two months or who report occasional use of prescription sleep aids that they are willing to discontinue; * have a current DSM-IV diagnosis of drug dependence other than nicotine or alcohol * are at risk for an alcohol withdrawal syndrome as evidenced by: * a history of seizures, delirium, or hallucinations during alcohol withdrawal * a Clinical Institute Withdrawal Assessment scale 62 score of \> 8, * report drinking to avoid withdrawal symptoms * have required medical treatment of alcohol withdrawal within the past 6 months * have used another investigational drug within 30 days or have used medications to treat alcohol (e.g., naltrexone, topiramate, acamprosate, disulfiram) or nicotine use (e.g., clonidine, varenicline, bupropion, nicotine replacement) in the past 3 months or intend to use these medications;prior use of nicotine replacement in situations where smoking is not permitted (e.g., planes) without the intention to quit smoking is not exclusionary; * intend to donate blood or blood products during the treatment phase of the study * have a Body Mass Index (calculated as weight in kilograms divided by the square of height in meters) less than 15 or greater than 39.99 or weight less than 45 kg; * are a female of childbearing potential who is pregnant, nursing, or not practicing effective contraception (oral, injectable, or implantable contraceptives, intrauterine device, or barrier method with spermicide).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Heavy Drinking Days During the Last 8 Weeks of Treatment | weeks 9-12 | The percentage of days of heavy drinking will be examined over the final 8 weeks of the study averaged by month (weeks 9-12 and weeks 13-16). A heavy drinking day is defined as 5 or more standard drinks for men and 4 or more standard drinks for women. A standard drink contains approximately 0.6 fluid ounces of pure alcohol. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Smoking Abstinence | Weeks 13-16 | Smoking abstinence is defined by self-reported abstinence from smoking for the last four weeks of treatment (weeks 13-16) and a urine cotinine level less than 15ng/mL measured at week 17. |
| Drinking Related Consequences | End of treatment (Week 17) | A self-report measure of negative consequences from drinking will be administered and the total score are analyzed. The ImBIBe, a measure of alcohol consequences based on the Drinker Inventory of Consequences (DRINC) was used. The DRINC total score has a range from 0-45, 45 being the highest score (or greatest number of negative consequences). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Sugar Pill Varenicline: 0.5 mg once per day for Days 1 to 3, 0.5 mg twice per day for Days 4 to 7, then two 0.5 mg tablets (1 mg) twice per day | 67 |
| Varenicline Varenicline: 0.5 mg once per day for Days 1 to 3, 0.5 mg twice per day for Days 4 to 7, then two 0.5 mg tablets (1 mg) twice per day | 64 |
| Total | 131 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 3 | 2 |
| Overall Study | Lost to Follow-up | 4 | 10 |
| Overall Study | Physician Decision | 2 | 3 |
| Overall Study | Scheduling Difficulties | 5 | 4 |
| Overall Study | Withdrawal by Subject | 2 | 3 |
Baseline characteristics
| Characteristic | Sugar Pill | Varenicline | Total |
|---|---|---|---|
| Age, Continuous | 41.8 years STANDARD_DEVIATION 11.7 | 43.6 years STANDARD_DEVIATION 11.7 | 42.7 years STANDARD_DEVIATION 11.7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 10 Participants | 5 Participants | 15 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 57 Participants | 59 Participants | 116 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 35 Participants | 34 Participants | 69 Participants |
| Race (NIH/OMB) More than one race | 8 Participants | 4 Participants | 12 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 24 Participants | 26 Participants | 50 Participants |
| Sex: Female, Male Female | 20 Participants | 19 Participants | 39 Participants |
| Sex: Female, Male Male | 47 Participants | 45 Participants | 92 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 64 | 0 / 67 |
| other Total, other adverse events | 47 / 64 | 46 / 67 |
| serious Total, serious adverse events | 2 / 64 | 0 / 67 |
Outcome results
Primary
Percentage of Heavy Drinking Days During the Last 8 Weeks of Treatment
The percentage of days of heavy drinking will be examined over the final 8 weeks of the study averaged by month (weeks 9-12 and weeks 13-16). A heavy drinking day is defined as 5 or more standard drinks for men and 4 or more standard drinks for women. A standard drink contains approximately 0.6 fluid ounces of pure alcohol.
Time frame: weeks 9-12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Varenicline | Percentage of Heavy Drinking Days During the Last 8 Weeks of Treatment | 2.07 log transformed percentage of days | Standard Error 0.23 |
| Placebo | Percentage of Heavy Drinking Days During the Last 8 Weeks of Treatment | 2.25 log transformed percentage of days | Standard Error 0.2 |
Primary
Percentage of Heavy Drinking Days During the Last 8 Weeks of Treatment
The percentage of days of heavy drinking will be examined over the final 8 weeks of the study averaged by month (weeks 9-12 and weeks 13-16). A heavy drinking day is defined as 5 or more standard drinks for men and 4 or more standard drinks for women. A standard drink contains approximately 0.6 fluid ounces of pure alcohol.
Time frame: weeks 13-16
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Varenicline | Percentage of Heavy Drinking Days During the Last 8 Weeks of Treatment | 1.99 log transformed percentage of days | Standard Error 0.22 |
| Placebo | Percentage of Heavy Drinking Days During the Last 8 Weeks of Treatment | 2.09 log transformed percentage of days | Standard Error 0.21 |
Primary
Percentage of Heavy Drinking Days During the Last 8 Weeks of Treatment
The percentage of days of heavy drinking will be examined over the final 8 weeks of the study. A heavy drinking day is defined as 5 or more standard drinks for men and 4 or more standard drinks for women. A standard drink contains approximately 0.6 fluid ounces of pure alcohol. Presented here is the average of the 8 weeks (reported as week 17 originally).
Time frame: 8 weeks
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Varenicline | Percentage of Heavy Drinking Days During the Last 8 Weeks of Treatment | 2.40 percentage of heavy drinking days | Standard Error 0.21 |
| Placebo | Percentage of Heavy Drinking Days During the Last 8 Weeks of Treatment | 2.28 percentage of heavy drinking days | Standard Error 0.21 |
Secondary
Drinking Related Consequences
A self-report measure of negative consequences from drinking will be administered and the total score are analyzed. The ImBIBe, a measure of alcohol consequences based on the Drinker Inventory of Consequences (DRINC) was used. The DRINC total score has a range from 0-45, 45 being the highest score (or greatest number of negative consequences).
Time frame: End of treatment (Week 17)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Varenicline | Drinking Related Consequences | 1.29 units on a scale | Standard Error 0.03 |
| Placebo | Drinking Related Consequences | 1.40 units on a scale | Standard Error 0.03 |
Secondary
Smoking Abstinence
Smoking abstinence is defined by self-reported abstinence from smoking for the last four weeks of treatment (weeks 13-16) and a urine cotinine level less than 15ng/mL measured at week 17.
Time frame: Weeks 13-16
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Varenicline | Smoking Abstinence | 8 Participants |
| Placebo | Smoking Abstinence | 0 Participants |