Nicotine Dependence
Conditions
Brief summary
To examine if switching from menthol to non-menthol cigarettes will change the dose-effect curves for positive subjective effects and alleviation of smoking urges as a function of nicotine delivery rate in smokers.
Detailed description
A placebo-controlled study that will recruit male and female menthol nicotine dependent smokers. Following screening and evaluation as described above, eligible participants will be enrolled in the study which will last about 4 weeks. Eligible, participants will be randomized to menthol or non-menthol smoking condition for 2 weeks (Phase 1) and then will be switched to the alternative condition for another 2 weeks (Phase 2). The smoking condition will be open label. Participants will be provided with free cigarettes in Phases 1 and 2. For the menthol condition, participants will be provided their usual brand of menthol cigarettes and for the non-menthol condition, they will be provided a matched-brand non-menthol cigarette (e.g., Newport Non-Menthol Gold 100s for those who smoke Newport Menthol Gold 100s). In week 2 of each Phase, participants will have a test session. Each session will include 3 infusions in the same order: nicotine (1 mg per 70 kg body weight) delivered over 5 minutes, saline and nicotine (1 mg/ 70 kg) delivered over 2.5 minutes. Once the participants complete the test session, participants will be crossed-over to the alternative treatment. The period between the 2 Phases will not be longer than one week.
Interventions
DRUGNicotine
session will include 3 infusions in the same order: nicotine (1 mg per 70 kg body weight) delivered over 5 minutes, saline and nicotine (1 mg/ 70 kg) delivered over 2.5 minutes.
Sponsors
National Institute on Drug Abuse (NIDA)
Yale University
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
HEALTH_SERVICES_RESEARCH
Masking
SINGLE (Subject)
Masking description
The cigarette condition is unblinded but the nicotine infusion is blinded to participant
Intervention model description
subjects will be unblinded to smoking menthol or non menthol for two weeks before each test session. Each session will include 3 infusions in the same order: nicotine (1 mg per 70 kg body weight) delivered over 5 minutes, saline and nicotine (1 mg/ 70 kg) delivered over 2.5 minutes. Once the participants complete the test session, participants will be crossed-over to the alternative treatment.
Eligibility
Sex/Gender
ALL
Age
21 Years to 35 Years
Healthy volunteers
No
Inclusion criteria
* 1\) Female and male smokers, aged 21 to 35 years, who have been smoking tobacco cigarettes for at least a year; * 2\) smoke ≥ 5 and less than 20 cigarettes per day; * 3\) urine cotinine levels \> 100 ng/mL consistent with nicotine intake of an active smoker * 4\) not seeking treatment at the time of the study for nicotine dependence; * 5\) in good health as verified by medical history, screening examination, and screening laboratory tests; * 6\) for women, not pregnant as determined by pregnancy screening, nor breast feeding, and using acceptable birth control methods.
Exclusion criteria
* 1\) history of major medical or psychiatric disorders that the physician investigator deems as contraindicated for the subject to be in the study; * 2\) regular use of psychotropic medication (antidepressants, antipsychotics, or anxiolytics); * 3\) current alcohol or substance dependence for any other recreational or prescription drugs other than nicotine; * 4\) use of e-cigarettes more than 10 days in the past 30 days; * 5\) urine drug screening indicating recent illicit drugs use (with the exception of marijuana).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Drug Effect Questionnaire - Stimulatory Effects | Following 2 weeks of smoking, the procedure took over 3 hours, with measured effects at 2.5 minutes, 5 minutes and 10 minutes | Drug Effects Questionnaire was used to assess participants. The DEQ is consist of 10 items measured on a 1 to 100 visual analog scale, ranging from not at all to extremely.. These ratings were then averaged to create three domain scores reflecting 1) stimulatory effects (average of feel stimulated, feel drug effects and feel high), 2) pleasurable effects (average of like, feel good and want more), and 3) aversive effects (average of feel anxious, feel down and feel bad). Head rush was also assessed. Scores on the subscales range from 0 - 100 where 0 is the measure of least impactful 'effect'. |
| Drug Effect Questionnaire - Pleasure Effect | Following 2 weeks of smoking, the procedure took over 3 hours, with measured effects at 2.5 minutes, 5 minutes and 10 minutes | Drug Effects Questionnaire was used to assess participants. The DEQ is consist of 10 items measured on a 1 to 100 visual analog scale, ranging from not at all to extremely.. These ratings were then averaged to create three domain scores reflecting: 1) stimulatory effects (average of feel stimulated, feel drug effects and feel high), 2) pleasurable effects (average of like, feel good and want more), and 3) aversive effects (average of feel anxious, feel down and feel bad). Head rush was also assessed. Scores on the subscales range from 0 - 100 where 0 is the measure of least impactful 'effect'. |
| Drug Effect Questionnaire - Aversive Effect | Following 2 weeks of smoking, the procedure took over 3 hours, with measured effects at 2.5 minutes, 5 minutes and 10 minutes | Drug Effects Questionnaire was used to assess participants. The DEQ is consist of 10 items measured on a 1 to 100 visual analog scale, ranging from not at all to extremely.. These ratings were then averaged to create three domain scores reflecting: 1) stimulatory effects (average of feel stimulated, feel drug effects and feel high), 2) pleasurable effects (average of like, feel good and want more), and 3) aversive effects (average of feel anxious, feel down and feel bad). Head rush was also assessed. Scores on the subscales range from 0 - 100 where 0 is the measure of least impactful 'effect'. |
| Drug Effect Questionnaire - Head Rush | Following 2 weeks of smoking, the procedure took over 3 hours, with measured effects at 2.5 minutes, 5 minutes and 10 minutes | Drug Effects Questionnaire was used to assess participants. The DEQ is consist of 10 items measured on a 1 to 100 visual analog scale, ranging from not at all to extremely.. These ratings were then averaged to create three domain scores reflecting: 1) stimulatory effects (average of feel stimulated, feel drug effects and feel high), 2) pleasurable effects (average of like, feel good and want more), and 3) aversive effects (average of feel anxious, feel down and feel bad). Head rush was also assessed. Scores on all subscales, including Head Rush scale, range from 0 - 100 where lower scores indicate less head rush. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| SAFTEE | up to one year | The SAFTEE is a technique for the systematic assessment of side effects in clinical trials developed by National Institute of Mental Health. It is a questionnaire that rates the current severity of a wide range of somatic, behavioral and affective symptoms in general and specific inquiry formats. It is designed to report adverse health events, regardless of whether or not they are suspected to be drug related, in order to reduce the under-reporting of unanticipated events compared with known or expected events. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Study Participants All participants in the study prior to randomization to crossover order. Eligible participants were individuals who reported smoking at least 5 cigarettes a day for the past year and had urine cotinine levels exceeding 100 ng/mL, an indicator of daily smoking. Participants were not interested in quitting smoking and were free of major medical and psychiatric disorders, including substance use disorders (except tobacco use), as confirmed by medical and psychiatric assessment. | 16 |
| Total | 16 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 3 | 1 |
Baseline characteristics
| Characteristic | Study Participants |
|---|---|
| Age, Continuous | 32.4 years STANDARD_DEVIATION 4.5 |
| Average number of cigarettes consumed daily | 10.5 cigarettes per day STANDARD_DEVIATION 4.7 |
| Fagerstrom Test for Nicotine Dependence (FTND) | 4.2 units on a scale STANDARD_DEVIATION 2.4 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 12 Participants |
| Race (NIH/OMB) More than one race | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 3 Participants |
| Region of Enrollment United States | 16 participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 16 | 0 / 13 |
| other Total, other adverse events | 0 / 16 | 0 / 13 |
| serious Total, serious adverse events | 0 / 16 | 0 / 13 |
Outcome results
Primary
Drug Effect Questionnaire - Aversive Effect
Drug Effects Questionnaire was used to assess participants. The DEQ is consist of 10 items measured on a 1 to 100 visual analog scale, ranging from not at all to extremely.. These ratings were then averaged to create three domain scores reflecting: 1) stimulatory effects (average of feel stimulated, feel drug effects and feel high), 2) pleasurable effects (average of like, feel good and want more), and 3) aversive effects (average of feel anxious, feel down and feel bad). Head rush was also assessed. Scores on the subscales range from 0 - 100 where 0 is the measure of least impactful 'effect'.
Time frame: Following 2 weeks of smoking, the procedure took over 3 hours, with measured effects at 2.5 minutes, 5 minutes and 10 minutes
Population: Participants assessed an any or both points in the crossover design.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Menthol | Drug Effect Questionnaire - Aversive Effect | 2.5 minutes | 11.33 units on a scale | Standard Deviation 11.78 |
| Menthol | Drug Effect Questionnaire - Aversive Effect | 5 minutes | 8.73 units on a scale | Standard Deviation 11.12 |
| Menthol | Drug Effect Questionnaire - Aversive Effect | 10 minutes | 6.33 units on a scale | Standard Deviation 8.5 |
| Non-Menthol | Drug Effect Questionnaire - Aversive Effect | 2.5 minutes | 14.76 units on a scale | Standard Deviation 15.56 |
| Non-Menthol | Drug Effect Questionnaire - Aversive Effect | 5 minutes | 11.23 units on a scale | Standard Deviation 13.78 |
| Non-Menthol | Drug Effect Questionnaire - Aversive Effect | 10 minutes | 6.92 units on a scale | Standard Deviation 8.79 |
Comparison: The fixed effects in the mixed models were infusion rate (2.5 minutes, 5 minutes and 10 minutes (placebo)), cigarette condition (menthol vs. non-menthol), and their interaction. We also controlled for order effects of cigarette condition by including session in the models Subject was a clustering factor and different variance-covariance structures were considered within each condition and subject. The best-fitting structure was selected based on Schwartz's Bayesian Criterion.p-value: 0.37Mixed Models Analysis
Primary
Drug Effect Questionnaire - Head Rush
Drug Effects Questionnaire was used to assess participants. The DEQ is consist of 10 items measured on a 1 to 100 visual analog scale, ranging from not at all to extremely.. These ratings were then averaged to create three domain scores reflecting: 1) stimulatory effects (average of feel stimulated, feel drug effects and feel high), 2) pleasurable effects (average of like, feel good and want more), and 3) aversive effects (average of feel anxious, feel down and feel bad). Head rush was also assessed. Scores on all subscales, including Head Rush scale, range from 0 - 100 where lower scores indicate less head rush.
Time frame: Following 2 weeks of smoking, the procedure took over 3 hours, with measured effects at 2.5 minutes, 5 minutes and 10 minutes
Population: Participants assessed an any or both points in the crossover design.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Menthol | Drug Effect Questionnaire - Head Rush | 2.5 minutes | 31.73 units on a scale | Standard Deviation 32.55 |
| Menthol | Drug Effect Questionnaire - Head Rush | 5 minutes | 19.20 units on a scale | Standard Deviation 25.48 |
| Menthol | Drug Effect Questionnaire - Head Rush | 10 minutes | 8.93 units on a scale | Standard Deviation 13.93 |
| Non-Menthol | Drug Effect Questionnaire - Head Rush | 2.5 minutes | 14.76 units on a scale | Standard Deviation 15.56 |
| Non-Menthol | Drug Effect Questionnaire - Head Rush | 5 minutes | 11.23 units on a scale | Standard Deviation 13.78 |
| Non-Menthol | Drug Effect Questionnaire - Head Rush | 10 minutes | 6.92 units on a scale | Standard Deviation 8.79 |
Comparison: The fixed effects in the mixed models were infusion rate (2.5 minutes, 5 minutes and 10 minutes (placebo)), cigarette condition (menthol vs. non-menthol), and their interaction. We also controlled for order effects of cigarette condition by including session in the models Subject was a clustering factor and different variance-covariance structures were considered within each condition and subject. The best-fitting structure was selected based on Schwartz's Bayesian Criterion.p-value: 0.2Mixed Models Analysis
Primary
Drug Effect Questionnaire - Pleasure Effect
Drug Effects Questionnaire was used to assess participants. The DEQ is consist of 10 items measured on a 1 to 100 visual analog scale, ranging from not at all to extremely.. These ratings were then averaged to create three domain scores reflecting: 1) stimulatory effects (average of feel stimulated, feel drug effects and feel high), 2) pleasurable effects (average of like, feel good and want more), and 3) aversive effects (average of feel anxious, feel down and feel bad). Head rush was also assessed. Scores on the subscales range from 0 - 100 where 0 is the measure of least impactful 'effect'.
Time frame: Following 2 weeks of smoking, the procedure took over 3 hours, with measured effects at 2.5 minutes, 5 minutes and 10 minutes
Population: Participants assessed an any or both points in the crossover design.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Menthol | Drug Effect Questionnaire - Pleasure Effect | 2.5 minutes | 37.51 units on a scale | Standard Deviation 28.35 |
| Menthol | Drug Effect Questionnaire - Pleasure Effect | 5 minutes | 36.49 units on a scale | Standard Deviation 31.55 |
| Menthol | Drug Effect Questionnaire - Pleasure Effect | 10 minutes | 23.42 units on a scale | Standard Deviation 20.8 |
| Non-Menthol | Drug Effect Questionnaire - Pleasure Effect | 2.5 minutes | 27.25 units on a scale | Standard Deviation 17.62 |
| Non-Menthol | Drug Effect Questionnaire - Pleasure Effect | 5 minutes | 29.28 units on a scale | Standard Deviation 25.42 |
| Non-Menthol | Drug Effect Questionnaire - Pleasure Effect | 10 minutes | 24.71 units on a scale | Standard Deviation 18.37 |
Comparison: The fixed effects in the mixed models were infusion rate (2.5 minutes, 5 minutes and 10 minutes (placebo)), cigarette condition (menthol vs. non-menthol), and their interaction. We also controlled for order effects of cigarette condition by including session in the models Subject was a clustering factor and different variance-covariance structures were considered within each condition and subject. The best-fitting structure was selected based on Schwartz's Bayesian Criterion.p-value: 0.68Mixed Models Analysis
Primary
Drug Effect Questionnaire - Stimulatory Effects
Drug Effects Questionnaire was used to assess participants. The DEQ is consist of 10 items measured on a 1 to 100 visual analog scale, ranging from not at all to extremely.. These ratings were then averaged to create three domain scores reflecting 1) stimulatory effects (average of feel stimulated, feel drug effects and feel high), 2) pleasurable effects (average of like, feel good and want more), and 3) aversive effects (average of feel anxious, feel down and feel bad). Head rush was also assessed. Scores on the subscales range from 0 - 100 where 0 is the measure of least impactful 'effect'.
Time frame: Following 2 weeks of smoking, the procedure took over 3 hours, with measured effects at 2.5 minutes, 5 minutes and 10 minutes
Population: Participants assessed an any or both points in the crossover design.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Menthol | Drug Effect Questionnaire - Stimulatory Effects | 2.5 Minutes | 39.37 units on a scale | Standard Deviation 24.41 |
| Menthol | Drug Effect Questionnaire - Stimulatory Effects | 5 minutes | 32.35 units on a scale | Standard Deviation 27.93 |
| Menthol | Drug Effect Questionnaire - Stimulatory Effects | 10 minutes | 13.19 units on a scale | Standard Deviation 16.15 |
| Non-Menthol | Drug Effect Questionnaire - Stimulatory Effects | 2.5 Minutes | 33.48 units on a scale | Standard Deviation 19.73 |
| Non-Menthol | Drug Effect Questionnaire - Stimulatory Effects | 5 minutes | 33.23 units on a scale | Standard Deviation 28.79 |
| Non-Menthol | Drug Effect Questionnaire - Stimulatory Effects | 10 minutes | 19.43 units on a scale | Standard Deviation 21.41 |
Comparison: The fixed effects in the mixed models were infusion rate (2.5 minutes, 5 minutes and 10 minutes (placebo)), cigarette condition (menthol vs. non-menthol), and their interaction. We also controlled for order effects of cigarette condition by including session in the models Subject was a clustering factor and different variance-covariance structures were considered within each condition and subject. The best-fitting structure was selected based on Schwartz's Bayesian Criterion.p-value: 0.93Mixed Models Analysis
Secondary
SAFTEE
The SAFTEE is a technique for the systematic assessment of side effects in clinical trials developed by National Institute of Mental Health. It is a questionnaire that rates the current severity of a wide range of somatic, behavioral and affective symptoms in general and specific inquiry formats. It is designed to report adverse health events, regardless of whether or not they are suspected to be drug related, in order to reduce the under-reporting of unanticipated events compared with known or expected events.
Time frame: up to one year
Population: these data were not collected