Smoking
Conditions
Keywords
smoking lapse behavior, smoking cessation, varenicline, naltrexone, medication effect on smoking lapse behavior
Brief summary
The purpose of this study is to examine how medications thought to attenuate the effects of alcohol (naltrexone) and smoking cessation medications (varenicline) affect the ability to resist smoking and also subsequent ad-lib smoking, following a low-dose alcohol priming drink, in non-treatment seeking alcohol-drinking daily smokers.
Interventions
DRUGnaltrexone
25 mg/day, with 1-week lead-in medication period. The starting dose is 0 mg/day for days 1-3, followed by 12.5mg/day for day 4, followed by 25mg/day for days 5-7, plus during the laboratory session (day 8).
DRUGvarenicline
2mg/day, with 1-week lead-in medication period. The starting dose is 0.5mg/day for days 1-2, followed by 0.5mg twice daily for days 3-5, followed by 1.0 mg twice daily for days 6-7, plus during the laboratory session (day 8).
DRUGplacebo
placebo
Sponsors
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Yale University
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
21 Years to 55 Years
Healthy volunteers
No
Inclusion criteria
* ages 21-55 * ability to read and write in English * alcohol-drinking smokers
Exclusion criteria
* any significant current medical conditions that would contraindicate smoking * current DSM-IV abuse or dependence of other substances, other than nicotine dependence or alcohol abuse. * positive test result at intake appointments on urine drug screens conducted for opiates, cocaine, or benzodiazepines * women who are pregnant or nursing * suicidal, homicidal or evidence of current severe mental illness * participants prescribed any psychotropic drug in the 30 days prior to study enrollment * blood donation within the past 6 weeks * individuals seeking treatment for smoking cessation or drinking or have attempted to quit smoking or drinking within the past 3 months * specific exclusion for administration of naltrexone not specified above including chronic pain conditions necessitating opioid treatment, and evidence of significant hepatocellular injury as evidenced by SGOT or SGPT \> 3x normal or elevated bilirubin * known allergy to varenicline or taking H2blockers (e.g., Cimetidine) * participation within the past 8 weeks in other studies that involve additive blood sampling and/or interventional measures that would be considered excessive in combination with the current protocol
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Latency to Initiate Ad-lib Smoking Session | day 8 | Time to smoking during the smoking delay task. Smoking delay task occurred on day 8 of the study. Range of time delay is 0 minutes to 50 minutes. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Cigarettes Smoked During the Ad-lib Period | day 8 | Number of cigarettes smoked during the ad libitum phase of the smoking delay task. Task occurred on day 8 of the study. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Naltrexone + Varenicline naltrexone (25mg) + varenicline (2mg)
naltrexone: 25 mg/day, with 1-week lead-in medication period. The starting dose is 0 mg/day for days 1-3, followed by 12.5mg/day for day 4, followed by 25mg/day for days 5-7, plus during the laboratory session (day 8).
varenicline: 2mg/day, with 1-week lead-in medication period. The starting dose is 0.5mg/day for days 1-2, followed by 0.5mg twice daily for days 3-5, followed by 1.0 mg twice daily for days 6-7, plus during the laboratory session (day 8). | 11 |
| Varenicline varenicline 2mg
varenicline: 2mg/day, with 1-week lead-in medication period. The starting dose is 0.5mg/day for days 1-2, followed by 0.5mg twice daily for days 3-5, followed by 1.0 mg twice daily for days 6-7, plus during the laboratory session (day 8). | 9 |
| Placebo placebo control
placebo: placebo | 10 |
| Total | 30 |
Baseline characteristics
| Characteristic | Naltrexone + Varenicline | Varenicline | Placebo | Total |
|---|---|---|---|---|
| Age, Continuous | 29.91 years STANDARD_DEVIATION 8.99 | 37.67 years STANDARD_DEVIATION 10.85 | 33.20 years STANDARD_DEVIATION 9.73 | 33.33 years STANDARD_DEVIATION 10.71 |
| Sex: Female, Male Female | 2 Participants | 2 Participants | 2 Participants | 6 Participants |
| Sex: Female, Male Male | 9 Participants | 7 Participants | 8 Participants | 24 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 11 | 0 / 9 | 0 / 10 |
| other Total, other adverse events | 3 / 11 | 5 / 9 | 4 / 10 |
| serious Total, serious adverse events | 0 / 11 | 0 / 9 | 0 / 10 |
Outcome results
Primary
Latency to Initiate Ad-lib Smoking Session
Time to smoking during the smoking delay task. Smoking delay task occurred on day 8 of the study. Range of time delay is 0 minutes to 50 minutes.
Time frame: day 8
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Naltrexone + Varenicline | Latency to Initiate Ad-lib Smoking Session | 28.134 minutes | Standard Error 5.328 |
| Varenicline | Latency to Initiate Ad-lib Smoking Session | 45.861 minutes | Standard Error 6.238 |
| Placebo | Latency to Initiate Ad-lib Smoking Session | 21.737 minutes | Standard Error 6.043 |
Secondary
Number of Cigarettes Smoked During the Ad-lib Period
Number of cigarettes smoked during the ad libitum phase of the smoking delay task. Task occurred on day 8 of the study.
Time frame: day 8
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Naltrexone + Varenicline | Number of Cigarettes Smoked During the Ad-lib Period | 1.283 cigarettes | Standard Error 0.283 |
| Varenicline | Number of Cigarettes Smoked During the Ad-lib Period | 0.959 cigarettes | Standard Error 0.331 |
| Placebo | Number of Cigarettes Smoked During the Ad-lib Period | 2.23 cigarettes | Standard Error 0.331 |