Alcohol Use Disorder, Nicotine Dependence
Conditions
Brief summary
This study is a double-blind, randomized clinical trial using a two group medication design consisting of the combination of VAR (1 mg twice daily) + NTX (50 mg once daily) and VAR (1 mg twice daily) + PLA (matched to NTX), for smoking cessation in a sample of heavy drinking daily smokers who want to quit smoking and reduce drinking.
Detailed description
This study is a double-blind, randomized clinical trial using a two group medication design consisting of the combination of VAR (1 mg twice daily) + NTX (50 mg once daily) and VAR (1 mg twice daily) + PLA (matched to NTX), for smoking cessation in a sample of heavy drinking daily smokers who want to quit smoking and reduce drinking. All participants will be daily smokers (≥ 5 cig/day) who are also heavy drinkers according to the National Institute on Alcohol Abuse and Alcoholism (NIAAA) guidelines: for men, \> 14 drinks per week or ≥ 5 drinks per occasion at least once per month over the past 12 months; for women, \> 7 drinks per week or ≥ 4 drinks per occasion at least once per month over the past 12 months. A total of 274 participants will be randomized, 137 to each medication group.
Interventions
DRUGVarenicline
Varenicline 1 mg twice daily
DRUGVarenicline plus Naltrexone
Varenicline 1 mg twice daily plus Naltrexone 50 mg once daily
Sponsors
National Institute on Drug Abuse (NIDA)
University of California, Los Angeles
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
21 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Be treatment-seeking for smoking cessation and have a desire to reduce or quit drinking 2. Be between the ages of 21 and 65 3. Be able to provide informed consent 4. Smoke 5 or more cigarettes per day for the past year 5. Currently drink heavily according to the National Institute on Alcohol Abuse and Alcoholism (NIAAA) guidelines: for men, \> 14 drinks per week or ≥ 5 drinks per occasion at least once per month over the past 12 months; for women, \> 7 drinks per week or ≥ 4 drinks per occasion at least once per month over the past 12 months 6. Pass the physical exam and associated laboratory tests, as determined by study physician
Exclusion criteria
1. Have clinically significant alcohol withdrawal, indicated by a score ≥ 10 on the Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar) and assessed at the in-person screening visits 2. Have lifetime DSM-V diagnosis of schizophrenia, bipolar disorder, a psychotic disorder, or any other psychiatric disorder as determined by the clinical interview 3. Have major depressive disorder within the past year requiring treatment as determined by the clinical interview using DSM-V criteria 4. Have a current or lifetime DSM-V diagnosis of a substance use disorder, other than for alcohol or nicotine, as determined by the clinical interview 5. Have a prior history of taking FDA approved medications (i.e. varenicline or bupropion) for smoking cessation 6. Be currently using any forms of nicotine replacement therapy (past use is acceptable) 7. Be currently using tobacco products other than cigarettes (such as e-cigarettes, cigars, or chewing tobacco) 8. Have a serious medical illness (significant cardiovascular disease; uncontrolled hypertension; hepatic or renal disease) that would contraindicate participation, as determined by the study physician 9. Be currently taking insulin or oral hypoglycemic medication 10. Be currently taking opioid pain medications or any form of opioid agonist maintenance therapy (such as methadone or buprenorphine) 11. Be currently taking any other psychoactive medications; such as anti-depressants, mood stabilizers, anti-seizure medications, sedatives-hypnotics, anxiolytics, stimulants or antipsychotics 12. Have self-reported use of cocaine, methamphetamine, heroin or other illicit drugs in the previous 60 days, verified by urine toxicology screen 13. For women, must not be pregnant (as indicated by self-report or a positive pregnancy test at any study visit), nursing, or planning to become pregnant while taking part in the study, and must agree to a reliable method of birth control
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Expired Carbon Monoxide Level <=5ppm | 26 weeks post-quit | Outcome for smoking cessation aim was Expired Carbon Monoxide level, which was used to determine whether a participant successfully abstained from cigarettes. 7 day point prevalence of nicotine abstinence was bioverified by Expired Carbon Monoxide reading of \<= 5ppm at the 26-week follow-up visit. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Drinks Per Drinking Day | 26 weeks post-quit | Outcome for drinking reduction aim - Number of Drinks per Drinking Day |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Varenicline Plus Naltrexone VAR (1 mg twice daily) + NTX (50 mg once daily)
Varenicline plus Naltrexone: Varenicline 1 mg twice daily plus Naltrexone 50 mg once daily | 83 |
| Varenicline VAR (1 mg twice daily)
Varenicline: Varenicline 1 mg twice daily | 82 |
| Total | 165 |
Baseline characteristics
| Characteristic | Varenicline Plus Naltrexone | Total | Varenicline |
|---|---|---|---|
| Age, Continuous | 41.24 years STANDARD_DEVIATION 12.42 | 41.55 years STANDARD_DEVIATION 12.06 | 42.07 years STANDARD_DEVIATION 11.75 |
| Alcohol Use Disorder Severity (Structured Clinical Interview for DSM-5) Mild | 27 Participants | 49 Participants | 22 Participants |
| Alcohol Use Disorder Severity (Structured Clinical Interview for DSM-5) Moderate | 19 Participants | 42 Participants | 23 Participants |
| Alcohol Use Disorder Severity (Structured Clinical Interview for DSM-5) None | 24 Participants | 48 Participants | 24 Participants |
| Alcohol Use Disorder Severity (Structured Clinical Interview for DSM-5) Severe | 12 Participants | 25 Participants | 13 Participants |
| Cigarettes per Smoking Day (Timeline Followback) | 14.21 cigarettes STANDARD_DEVIATION 8.39 | 14.16 cigarettes STANDARD_DEVIATION 8.07 | 14.10 cigarettes STANDARD_DEVIATION 7.79 |
| Drinking Days (Timeline Followback) | 20.71 days STANDARD_DEVIATION 8.08 | 20.17 days STANDARD_DEVIATION 8 | 19.63 days STANDARD_DEVIATION 7.92 |
| Drinks per Drinking Day (Timeline Followback) | 6.50 drinks per drinking day STANDARD_DEVIATION 4.65 | 6.47 drinks per drinking day STANDARD_DEVIATION 4.22 | 6.44 drinks per drinking day STANDARD_DEVIATION 3.76 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 12 Participants | 25 Participants | 13 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 71 Participants | 140 Participants | 69 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Expired Alveolar CO Level (ppm) | 11.65 ppm STANDARD_DEVIATION 6.25 | 10.67 ppm STANDARD_DEVIATION 6.86 | 9.68 ppm STANDARD_DEVIATION 7.34 |
| Fagerstrom Test for Nicotine Dependence (FTND) Score | 4.64 units on a scale STANDARD_DEVIATION 2.26 | 4.63 units on a scale STANDARD_DEVIATION 2.3 | 4.61 units on a scale STANDARD_DEVIATION 2.35 |
| Heavy Drinking Days (Timeline Followback) | 12.87 heavy drinking days STANDARD_DEVIATION 9.55 | 12.59 heavy drinking days STANDARD_DEVIATION 9.18 | 12.30 heavy drinking days STANDARD_DEVIATION 8.84 |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 4 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 40 Participants | 76 Participants | 36 Participants |
| Race (NIH/OMB) More than one race | 5 Participants | 12 Participants | 7 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 2 Participants | 3 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 4 Participants | 12 Participants | 8 Participants |
| Race (NIH/OMB) White | 27 Participants | 56 Participants | 29 Participants |
| Region of Enrollment United States | 83 Participants | 165 Participants | 82 Participants |
| Sex: Female, Male Female | 31 Participants | 63 Participants | 32 Participants |
| Sex: Female, Male Male | 52 Participants | 102 Participants | 50 Participants |
| Smoking Days (Timeline Followback) | 28.94 days STANDARD_DEVIATION 3.37 | 29.16 days STANDARD_DEVIATION 2.61 | 29.39 days STANDARD_DEVIATION 1.49 |
| Urine Cotinine Levels (ng/ml) | 5.50 ng/ml STANDARD_DEVIATION 1.14 | 5.44 ng/ml STANDARD_DEVIATION 1.09 | 5.37 ng/ml STANDARD_DEVIATION 1.05 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 83 | 0 / 82 |
| other Total, other adverse events | 63 / 83 | 64 / 82 |
| serious Total, serious adverse events | 0 / 83 | 0 / 82 |
Outcome results
Primary
Number of Participants With Expired Carbon Monoxide Level <=5ppm
Outcome for smoking cessation aim was Expired Carbon Monoxide level, which was used to determine whether a participant successfully abstained from cigarettes. 7 day point prevalence of nicotine abstinence was bioverified by Expired Carbon Monoxide reading of \<= 5ppm at the 26-week follow-up visit.
Time frame: 26 weeks post-quit
Population: Intent to Treat.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Varenicline Plus Naltrexone | Number of Participants With Expired Carbon Monoxide Level <=5ppm | 22 Participants |
| Varenicline | Number of Participants With Expired Carbon Monoxide Level <=5ppm | 37 Participants |
Secondary
Drinks Per Drinking Day
Outcome for drinking reduction aim - Number of Drinks per Drinking Day
Time frame: 26 weeks post-quit
Population: Intent to Treat
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Varenicline Plus Naltrexone | Drinks Per Drinking Day | 3.1242 drinks per drinking day | Standard Error 1.0281 |
| Varenicline | Drinks Per Drinking Day | 3.5121 drinks per drinking day | Standard Error 0.9594 |