Nicotine Dependence
Conditions
Brief summary
To examine the acute reinforcing effects of menthol, a fruit flavor (green apple) or a fruit flavor plus menthol, alone or in combination with nicotine in smokers. Flavors will be administered by inhalation via electronic cigarettes (e-cigarettes) and nicotine will be administered intravenously. The reinforcing drug effects will be measured with the drug effects questionnaire (DEQ).
Detailed description
This is a proposed double-blind, crossover study that enrolls young adult smokers who prefer menthol cigarettes. The study will consist of an adaptation session and three test sessions. In the adaptation session, participants will practice using the e-cigarette by sampling the flavors to be used in the test sessions. The test sessions will be performed following overnight abstinence from tobacco. Across the three test sessions, participants will be assigned to a random sequence of the three different e-cigarette conditions: menthol, green apple or menthol plus green apple, a different flavor condition for each test session. In each test session, just after the assigned flavor is delivered via the e-cigarette, participants will receive a random order of one intravenous delivery of saline, and two intravenous deliveries of nicotine (3.6 mcg/kg and 7 mcg/kg or 0.25 mg/70 kg and 0.5 mg/70kg), one hour apart. The test sessions will be performed at least 24 hours apart to minimize carryover nicotine effects. The main outcome measure will be subjective drug effects as measured with the Drug Effects Questionnaire (DEQ). Other outcomes include cardiovascular measures, cognitive performance, and self-report measures of nicotine withdrawal and craving. Cardiovascular measures include heart rate, systolic and diastolic blood pressure. Cognitive performance will be assessed with the Stroop test, mathematical processing test (MPT), and continuous performance test (CPT). Nicotine withdrawal measures will be measured with the Minnesota Nicotine Withdrawal Symptom Checklist (M-NWSC) and the Brief Questionnaire on Smoking Urges (BQSU).
Interventions
DRUGIV nicotine
Subjects in each arm will receive three infusions in a random order one hour apart. The infusions will be saline, 0.25mg/70kg and 0.5mg/70kg
DRUGMenthol flavor
American e-liquids' menthol flavor used in e-cigarettes will be used as the placebo comparator
DRUGgreen apple
green apple will be added to the menthol flavor
DRUGgreen apple and menthol
menthol and green apple will be the active intervention
Sponsors
National Institute on Drug Abuse (NIDA)
Yale University
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
HEALTH_SERVICES_RESEARCH
Masking
DOUBLE (Subject, Investigator)
Masking description
The participant and medical professional will be blinded to the condition per day.
Intervention model description
Mixed-effects models will be used to test the study hypotheses. These models allow for different numbers of observations per subject, use all available data on each subject, and are unaffected by randomly missing data.
Eligibility
Sex/Gender
ALL
Age
18 Years to 30 Years
Healthy volunteers
No
Inclusion criteria
Female and male mentholated cigarette smokers, aged 18 to 30 years; history of smoking for the past 12 months, at least one cigarette per day; smoking status is verified with urinary cotinine levels above 10 ng/ml; not seeking treatment for nicotine dependence at the time of study entry in good health as verified by medical history, screening examination, and screening laboratory tests; for women, not pregnant as determined by pregnancy screening, nor breast feeding, and using acceptable birth control methods.
Exclusion criteria
History of major medical illnesses that the physician investigator deems as contraindicated for the patient to be in the study; regular use of psychotropic medication (antidepressants, antipsychotics, or anxiolytics); psychiatric diagnosis and / or treatment for Axis I disorders including major depression, bipolar affective disorder, schizophrenia or panic disorder in the past month; abuse of alcohol or any other recreational or prescription drugs in the past 30 days; any allergy to propylene glycol or menthol; and 6) aversion to green apple flavor.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Reinforcing Drug Effects Will be Measured With the Drug Effects Questionnaire (DEQ). | up to 3 hours per test session. | The (DEQ) Drug Effects Questionnaire has eleven questions with a minimum score of 0 to a maximum score of 100. Peak values from each time points were calculated for the change in the intensity of positive subjective effects as measured with these peak values for like and want more were averaged to obtain a summary score to represent the feel good drug effects composite factor. Higher scores for each DEQ represent greater endorsement of that subjective effect (e.g., on the like drug scale a response of 90 represents greater liking than a response of 50). |
Countries
United States
Participant flow
Recruitment details
A total of 26 subjects were eligible for participation with 24 randomized after completion of the adaptation session. Reasons for exclusion after adaptation session included poor venous access (n=1) and a positive drug screen (n=1).
Pre-assignment details
A total of 26 subjects were eligible for participation with 24 randomized after completion of the adaptation session.
Participants by arm
| Arm | Count |
|---|---|
| Overall Study The baseline characteristics has been provided for the entire study. Test sessions were randomized by arm, each test session was a different arm. | 24 |
| Total | 24 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Physician Decision | 1 |
| Overall Study | Protocol Violation | 1 |
Baseline characteristics
| Characteristic | Overall Study |
|---|---|
| Age, Continuous | 26.2 years STANDARD_DEVIATION 2.4 |
| Average cigarette consumption per day | 8.3 cigarette STANDARD_DEVIATION 4.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 18 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Fagerstrom Test of Nicotine Dependence | 3.2 units on a scale STANDARD_DEVIATION 2.1 |
| Positive THC at screen | 15 participants |
| Race/Ethnicity, Customized African American | 15 Participants |
| Race/Ethnicity, Customized Caucasian | 7 Participants |
| Race/Ethnicity, Customized Hispanic ethnicity | 6 Participants |
| Race/Ethnicity, Customized Other | 4 Participants |
| serum cotinine level | 194.4 ng/ml STANDARD_DEVIATION 123.8 |
| Sex: Female, Male Female | 9 Participants |
| Sex: Female, Male Male | 15 Participants |
| Years of smoking | 13.2 years STANDARD_DEVIATION 2.4 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 22 | 0 / 20 | 0 / 20 |
| other Total, other adverse events | 0 / 22 | 0 / 18 | 0 / 20 |
| serious Total, serious adverse events | 0 / 22 | 0 / 20 | 0 / 20 |
Outcome results
Primary
The Reinforcing Drug Effects Will be Measured With the Drug Effects Questionnaire (DEQ).
The (DEQ) Drug Effects Questionnaire has eleven questions with a minimum score of 0 to a maximum score of 100. Peak values from each time points were calculated for the change in the intensity of positive subjective effects as measured with these peak values for like and want more were averaged to obtain a summary score to represent the feel good drug effects composite factor. Higher scores for each DEQ represent greater endorsement of that subjective effect (e.g., on the like drug scale a response of 90 represents greater liking than a response of 50).
Time frame: up to 3 hours per test session.
Population: Data was analyzed as Intention to Treat
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Menthol E-liquid | The Reinforcing Drug Effects Will be Measured With the Drug Effects Questionnaire (DEQ). | Higher Nicotine : Max_Cool | 43.18 units on a scale | Standard Deviation 26.49 |
| Menthol E-liquid | The Reinforcing Drug Effects Will be Measured With the Drug Effects Questionnaire (DEQ). | Saline: Max_Like | 33.00 units on a scale | Standard Deviation 30.67 |
| Menthol E-liquid | The Reinforcing Drug Effects Will be Measured With the Drug Effects Questionnaire (DEQ). | Lower Nicotine: Max_Craving | 48.00 units on a scale | Standard Deviation 35.69 |
| Menthol E-liquid | The Reinforcing Drug Effects Will be Measured With the Drug Effects Questionnaire (DEQ). | Lower Nicotine: Max_Cool | 33.27 units on a scale | Standard Deviation 26.16 |
| Menthol E-liquid | The Reinforcing Drug Effects Will be Measured With the Drug Effects Questionnaire (DEQ). | Higher Nicotine : Max_Dislike | 24.36 units on a scale | Standard Deviation 29.86 |
| Menthol E-liquid | The Reinforcing Drug Effects Will be Measured With the Drug Effects Questionnaire (DEQ). | Saline: Max_Cool | 31.45 units on a scale | Standard Deviation 21.97 |
| Menthol E-liquid | The Reinforcing Drug Effects Will be Measured With the Drug Effects Questionnaire (DEQ). | Higher Nicotine : Max_Craving | 41.27 units on a scale | Standard Deviation 35.29 |
| Menthol E-liquid | The Reinforcing Drug Effects Will be Measured With the Drug Effects Questionnaire (DEQ). | Saline: Max_Craving | 46.09 units on a scale | Standard Deviation 39.44 |
| Menthol E-liquid | The Reinforcing Drug Effects Will be Measured With the Drug Effects Questionnaire (DEQ). | Lower Nicotine: Max_Like | 46.09 units on a scale | Standard Deviation 31.02 |
| Menthol E-liquid | The Reinforcing Drug Effects Will be Measured With the Drug Effects Questionnaire (DEQ). | Higher Nicotine : Max_Like | 56.00 units on a scale | Standard Deviation 28.14 |
| Menthol E-liquid | The Reinforcing Drug Effects Will be Measured With the Drug Effects Questionnaire (DEQ). | Saline: Max_Dislike | 8.72 units on a scale | Standard Deviation 12.64 |
| Menthol E-liquid | The Reinforcing Drug Effects Will be Measured With the Drug Effects Questionnaire (DEQ). | Lower Nicotine: Max_Dislike | 13.63 units on a scale | Standard Deviation 17.48 |
| Green Apple E-liquid | The Reinforcing Drug Effects Will be Measured With the Drug Effects Questionnaire (DEQ). | Saline: Max_Cool | 15.50 units on a scale | Standard Deviation 20.56 |
| Green Apple E-liquid | The Reinforcing Drug Effects Will be Measured With the Drug Effects Questionnaire (DEQ). | Higher Nicotine : Max_Craving | 46.00 units on a scale | Standard Deviation 36.57 |
| Green Apple E-liquid | The Reinforcing Drug Effects Will be Measured With the Drug Effects Questionnaire (DEQ). | Lower Nicotine: Max_Cool | 17.47 units on a scale | Standard Deviation 22.45 |
| Green Apple E-liquid | The Reinforcing Drug Effects Will be Measured With the Drug Effects Questionnaire (DEQ). | Lower Nicotine: Max_Like | 50.11 units on a scale | Standard Deviation 30.44 |
| Green Apple E-liquid | The Reinforcing Drug Effects Will be Measured With the Drug Effects Questionnaire (DEQ). | Lower Nicotine: Max_Dislike | 13.36 units on a scale | Standard Deviation 21.65 |
| Green Apple E-liquid | The Reinforcing Drug Effects Will be Measured With the Drug Effects Questionnaire (DEQ). | Lower Nicotine: Max_Craving | 53.16 units on a scale | Standard Deviation 37.34 |
| Green Apple E-liquid | The Reinforcing Drug Effects Will be Measured With the Drug Effects Questionnaire (DEQ). | Saline: Max_Like | 35.80 units on a scale | Standard Deviation 31.65 |
| Green Apple E-liquid | The Reinforcing Drug Effects Will be Measured With the Drug Effects Questionnaire (DEQ). | Saline: Max_Dislike | 15.50 units on a scale | Standard Deviation 23.75 |
| Green Apple E-liquid | The Reinforcing Drug Effects Will be Measured With the Drug Effects Questionnaire (DEQ). | Saline: Max_Craving | 57.70 units on a scale | Standard Deviation 36.6 |
| Green Apple E-liquid | The Reinforcing Drug Effects Will be Measured With the Drug Effects Questionnaire (DEQ). | Higher Nicotine : Max_Dislike | 25.88 units on a scale | Standard Deviation 31.41 |
| Green Apple E-liquid | The Reinforcing Drug Effects Will be Measured With the Drug Effects Questionnaire (DEQ). | Higher Nicotine : Max_Cool | 26.22 units on a scale | Standard Deviation 25.83 |
| Green Apple E-liquid | The Reinforcing Drug Effects Will be Measured With the Drug Effects Questionnaire (DEQ). | Higher Nicotine : Max_Like | 53.44 units on a scale | Standard Deviation 28.03 |
| Green Apple and Menthol E-liquid | The Reinforcing Drug Effects Will be Measured With the Drug Effects Questionnaire (DEQ). | Higher Nicotine : Max_Like | 50.80 units on a scale | Standard Deviation 34.69 |
| Green Apple and Menthol E-liquid | The Reinforcing Drug Effects Will be Measured With the Drug Effects Questionnaire (DEQ). | Saline: Max_Dislike | 14.40 units on a scale | Standard Deviation 23.79 |
| Green Apple and Menthol E-liquid | The Reinforcing Drug Effects Will be Measured With the Drug Effects Questionnaire (DEQ). | Lower Nicotine: Max_Cool | 25.90 units on a scale | Standard Deviation 26.66 |
| Green Apple and Menthol E-liquid | The Reinforcing Drug Effects Will be Measured With the Drug Effects Questionnaire (DEQ). | Higher Nicotine : Max_Cool | 25.20 units on a scale | Standard Deviation 21.38 |
| Green Apple and Menthol E-liquid | The Reinforcing Drug Effects Will be Measured With the Drug Effects Questionnaire (DEQ). | Saline: Max_Craving | 55.80 units on a scale | Standard Deviation 38.24 |
| Green Apple and Menthol E-liquid | The Reinforcing Drug Effects Will be Measured With the Drug Effects Questionnaire (DEQ). | Higher Nicotine : Max_Dislike | 20.80 units on a scale | Standard Deviation 27.59 |
| Green Apple and Menthol E-liquid | The Reinforcing Drug Effects Will be Measured With the Drug Effects Questionnaire (DEQ). | Lower Nicotine: Max_Craving | 49.00 units on a scale | Standard Deviation 37.95 |
| Green Apple and Menthol E-liquid | The Reinforcing Drug Effects Will be Measured With the Drug Effects Questionnaire (DEQ). | Saline: Max_Cool | 24.60 units on a scale | Standard Deviation 22.96 |
| Green Apple and Menthol E-liquid | The Reinforcing Drug Effects Will be Measured With the Drug Effects Questionnaire (DEQ). | Lower Nicotine: Max_Dislike | 14.50 units on a scale | Standard Deviation 23.45 |
| Green Apple and Menthol E-liquid | The Reinforcing Drug Effects Will be Measured With the Drug Effects Questionnaire (DEQ). | Higher Nicotine : Max_Craving | 49.90 units on a scale | Standard Deviation 36.9 |
| Green Apple and Menthol E-liquid | The Reinforcing Drug Effects Will be Measured With the Drug Effects Questionnaire (DEQ). | Saline: Max_Like | 32.90 units on a scale | Standard Deviation 27.04 |
| Green Apple and Menthol E-liquid | The Reinforcing Drug Effects Will be Measured With the Drug Effects Questionnaire (DEQ). | Lower Nicotine: Max_Like | 42.90 units on a scale | Standard Deviation 32.4 |