Nicotine Dependence
Conditions
Brief summary
A placebo-controlled study to enroll male and female tobacco smokers who will participate in five experimental sessions. subjects will be given an IV infusion of either saline or 1 mg nicotine at rapid, moderate or slow infusion rates (nicotine at 0.24,0.096, 0.048 and 0.024, mcg per kg body weight per sec).
Detailed description
A placebo-controlled study that will enroll male and female tobacco smokers' menthol to participate in five experimental sessions. During the experimental session, subjects will be given an IV infusion of either saline or 1 mg nicotine at rapid, moderate or slow infusion rates (nicotine at 0.24,0.096, 0.048 and 0.024, mcg per kg body weight per sec). The infusion conditions for each experimental session will be determined in random order. Aim 1 is to establish a dose-effect curve for positive subjective effects (drug liking and good drug effects) and alleviation of smoking urges, as a function of nicotine delivery rate in menthol and non-menthol cigarette preferring smokers Aim 2 is to establish a dose-effect curve positive subjective effects and alleviation of smoking urges as a function of nicotine delivery rate. Aim 3 is to establish a dose-effect curve for nicotine's effect to alleviate symptoms of nicotine withdrawal in abstinent smokers as a function of nicotine delivery rate. Aim 4 is to establish a dose-effect curve for nicotine's acute cardiovascular health effects. Data from this project will help to establish benchmark values for nicotine's threshold effects that will guide policies on the nicotine yield of tobacco products. Presented is the time frame at which the peak change was strongest by treatment arm. The possible peak numbers could be 1, 3, 5, 7 and 10 minutes.
Interventions
DRUGNicotine saline infusion 0.00mcg/kg/s
saline 0.00mcg/kg/s
DRUGNicotine infusion 0.24mcg/kg/s
nicotine 0.24mcg/kg/s
DRUGNicotine infusion 0.096mcg/kg/s
nicotine 0.096mcg/kg/s
DRUGNicotine infusion 0.048 mcg/kg/s
nicotine 0.048mcg/kg/s
DRUGNicotine infusion 0.024mcg/kg/s
nicotine 0.024mcg/kg/s
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
Participant will not know nicotine dose or rate of infusion.
Intervention model description
Single blind, placebo-controlled, mixed-design with nicotine delivery as a within-subjects factor.
Eligibility
Sex/Gender
ALL
Age
18 Years to 35 Years
Healthy volunteers
No
Inclusion criteria
* Female and male smokers, aged 18 to 35 years, who have been smoking tobacco cigarettes for at least a year * Smoke ≥ 5 and less than 20 cigarettes per day; * Urine cotinine levels \> 100 ng/mL consistent with nicotine intake of an active smoker (23) * Not seeking treatment at the time of the study for nicotine dependence; * 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 or psychiatric disorders that the physician investigator deems as contraindicated for the subject to be in the study * Regular use of psychotropic medication (antidepressants, antipsychotics, or anxiolytics) * Current alcohol or substance dependence for any other recreational or prescription drugs other than nicotine * Use of e-cigarettes more than 10 days in the past 30 days * Urine drug screening indicating recent illicit drugs use (with the exception of marijuana).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Peak Changes on Items of the Drug Effects Questionnaire (DEQ) - Stimulatory Effects | up to 10 minutes | The peak change in the intensity of subjective effects as measured by the DEQ: Drug stimulatory effects questionnaire; Eleven questions with a minimum score of 0 to a maximum score of 100. Presented is the DEQ score at which the peak change was strongest by treatment arm. Each session took approximately 60 minutes, however the measures were only collected up to 10 minutes post infusion. This correction to the outcome time frame was made when the results were entered. Data were collected at 1, 3, 5, 7 and 10 minute intervals. The outcome measure title DEQ Stimulatory Effects measure was also updated. |
| Peak Changes on Items of the Drug Effects Questionnaire (DEQ) - Pleasurable Effects | up to 10 minutes post infusion | The peak change in the intensity of subjective effects as measured by the DEQ: Drug pleasurable effects questionnaire; Eleven questions with a minimum score of 0 to a maximum score of 100. Presented is the DEQ score at which the peak change was strongest by treatment arm. Each session took approximately 60 minutes, however the measures were only collected up to 10 minutes post infusion. This correction to the outcome time frame was made when the results were entered. Data were collected at 1, 3, 5, 7 and 10 minute intervals. The outcome measure title DEQ Stimulatory Effects measure was also updated. |
Countries
United States
Participant flow
Pre-assignment details
24 subjects were randomized, yet two subjects didn't complete all five days. Therefore, some conditions have 23 participants, and some have 22.
Participants by arm
| Arm | Count |
|---|---|
| Overall Baseline Characteristics Baseline characteristics of all participants prior to randomization. | 24 |
| Total | 24 |
Baseline characteristics
| Characteristic | Overall Baseline Characteristics |
|---|---|
| Age, Continuous | 28.1 years STANDARD_DEVIATION 3.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 20 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race/Ethnicity, Customized Black | 14 Participants |
| Race/Ethnicity, Customized Native American | 1 Participants |
| Race/Ethnicity, Customized Other | 2 Participants |
| Race/Ethnicity, Customized White | 7 Participants |
| Sex: Female, Male Female | 11 Participants |
| Sex: Female, Male Male | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 22 | 0 / 23 | 0 / 23 | 0 / 22 | 0 / 23 |
| other Total, other adverse events | 0 / 22 | 0 / 23 | 0 / 23 | 0 / 22 | 0 / 23 |
| serious Total, serious adverse events | 0 / 22 | 0 / 23 | 0 / 23 | 0 / 22 | 0 / 23 |
Outcome results
Primary
Peak Changes on Items of the Drug Effects Questionnaire (DEQ) - Pleasurable Effects
The peak change in the intensity of subjective effects as measured by the DEQ: Drug pleasurable effects questionnaire; Eleven questions with a minimum score of 0 to a maximum score of 100. Presented is the DEQ score at which the peak change was strongest by treatment arm. Each session took approximately 60 minutes, however the measures were only collected up to 10 minutes post infusion. This correction to the outcome time frame was made when the results were entered. Data were collected at 1, 3, 5, 7 and 10 minute intervals. The outcome measure title DEQ Stimulatory Effects measure was also updated.
Time frame: up to 10 minutes post infusion
Population: Intention to treat analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Randomized Participants | Peak Changes on Items of the Drug Effects Questionnaire (DEQ) - Pleasurable Effects | nicotine saline infusion 0.00mcg/kg/s | 8.83 score on a scale | Standard Error 5.09 |
| Randomized Participants | Peak Changes on Items of the Drug Effects Questionnaire (DEQ) - Pleasurable Effects | nicotine infusion 0.24mcg/kg/s | 30.36 score on a scale | Standard Error 4.96 |
| Randomized Participants | Peak Changes on Items of the Drug Effects Questionnaire (DEQ) - Pleasurable Effects | nicotine infusion 0.096mcg/kg/s | 36.73 score on a scale | Standard Error 4.97 |
| Randomized Participants | Peak Changes on Items of the Drug Effects Questionnaire (DEQ) - Pleasurable Effects | nicotine infusion 0.048mcg/kg/s | 26 score on a scale | Standard Error 5 |
| Randomized Participants | Peak Changes on Items of the Drug Effects Questionnaire (DEQ) - Pleasurable Effects | nicotine infusion 0.024mcg/kg/s | 21.19 score on a scale | Standard Error 4.89 |
Primary
Peak Changes on Items of the Drug Effects Questionnaire (DEQ) - Stimulatory Effects
The peak change in the intensity of subjective effects as measured by the DEQ: Drug stimulatory effects questionnaire; Eleven questions with a minimum score of 0 to a maximum score of 100. Presented is the DEQ score at which the peak change was strongest by treatment arm. Each session took approximately 60 minutes, however the measures were only collected up to 10 minutes post infusion. This correction to the outcome time frame was made when the results were entered. Data were collected at 1, 3, 5, 7 and 10 minute intervals. The outcome measure title DEQ Stimulatory Effects measure was also updated.
Time frame: up to 10 minutes
Population: Intention to treat analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Randomized Participants | Peak Changes on Items of the Drug Effects Questionnaire (DEQ) - Stimulatory Effects | nicotine saline infusion 0.00mcg/kg/s | 7.03 score on a scale | Standard Error 5.34 |
| Randomized Participants | Peak Changes on Items of the Drug Effects Questionnaire (DEQ) - Stimulatory Effects | nicotine infusion 0.24mcg/kg/s | 37.48 score on a scale | Standard Error 5.14 |
| Randomized Participants | Peak Changes on Items of the Drug Effects Questionnaire (DEQ) - Stimulatory Effects | nicotine infusion 0.096mcg/kg/s | 41.91 score on a scale | Standard Error 5.15 |
| Randomized Participants | Peak Changes on Items of the Drug Effects Questionnaire (DEQ) - Stimulatory Effects | nicotine infusion 0.048mcg/kg/s | 28.22 score on a scale | Standard Error 5.22 |
| Randomized Participants | Peak Changes on Items of the Drug Effects Questionnaire (DEQ) - Stimulatory Effects | nicotine infusion 0.024mcg/kg/s | 22.12 score on a scale | Standard Error 5.05 |