Tobacco Dependence
Conditions
Keywords
Smoking, Nicotine
Brief summary
The overall aim of this project is to evaluate the effect of progressive nicotine reduction in cigarettes on smoking behavior, toxin exposure and psychiatric symptoms in smokers with comorbid mood and/or anxiety disorders. Smokers with mood and/or anxiety disorder will smoke research cigarettes that will contain either a) nicotine content similar to their preferred usual brand of cigarettes, or b) nicotine content per cigarette that is progressively reduced from approximately 11.6 mg to 0.2 mg per cigarette over 18 weeks. It is our hypothesis that nicotine intake will decline as a function of cigarette nicotine content in the Reduced Nicotine Content group without significant increases in tobacco smoke exposure, severity of nicotine withdrawal symptoms, mood and anxiety symptomatology or protocol non-adherence over time in the Reduced Nicotine Content group as compared with the control group.
Detailed description
The overall aim of this project is to evaluate the effect of progressive nicotine reduction in cigarettes on smoking behavior, toxicant exposure and psychiatric symptoms in smokers with comorbid mood and/or anxiety disorders. To do so, we will randomly assign 200 adult smokers with a unipolar mood and/or anxiety disorder within the past year to smoke research cigarettes that will contain either a) Usual Nicotine Content (UNC): nicotine content similar to their preferred usual brand of cigarettes, or b) Reduced Nicotine Content (RNC): nicotine content per cigarette is progressively reduced from approximately 11.6 mg to 0.2 mg per cigarette over 18 weeks. All subjects will participate in baseline periods prior to double-blind randomization to assess normal smoking behavior and then to establish ability to tolerate research cigarettes prior to randomization. A total of 280 participants will be enrolled in the study at two sites with the aim of randomizing 200 who complete the baseline phase. 100 participants will be enrolled in the randomized phase at Penn State Hershey and 100 at the Massachusetts General Hospital site. Participants will be started on the study protocol during Baseline I and Baseline II but will be removed from the study if they are not able to comply with the protocol. We expect that approximately 40 participants at each site drop out from the study prior to randomization (due to inability to comply with study protocol). It is our hypothesis that nicotine intake, as measured by plasma cotinine concentration, will decline as a function of cigarette nicotine content in the RNC group. Further, it is our hypothesis that by gradually reducing the nicotine content of the cigarettes in a step-wise fashion, there will not be significant increases in biomarkers of tobacco smoke exposure, severity of nicotine withdrawal symptoms, mood and anxiety symptomatology or protocol non-adherence over time in the experimental group (RNC) as compared with the UNC control group.
Interventions
Research cigarettes will have gradually reduced nicotine content
DRUGUsual Nicotine Content Cigarettes
Usual Nicotine Content Cigarettes
Sponsors
National Institute on Drug Abuse (NIDA)
Milton S. Hershey Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
HEALTH_SERVICES_RESEARCH
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Smoke \>4 cigarettes/day for at least a year * No quit attempt in prior month * Not planning to quit smoking within next 6 months * Plan to live in local area for next 8 months * Meet diagnostic criteria for a current or lifetime Anxiety Disorder or Mood Disorder as determined by the Mini-international Neuropsychiatric Interview * Read and write in English * Women not pregnant or nursing and taking steps to avoid pregnancy * Able to understand and consent to study procedures
Exclusion criteria
* Unstable or significant medical condition such as Chronic Obstructive Pulmonary Disease or kidney failure * Use of non-cigarette nicotine delivery product in the past week or smoking cessation medicine in prior month * Currently reducing or planning to reduce cigarette consumption in next month * Uncontrolled serious psychotic illness or substance abuse or inpatient treatment for these in the past 6 months * Current suicide risk on clinical assessment * Aged \<18 or \>65 * History of difficulty providing blood samples (fainting, poor venous access) * Unwilling to remain on one flavor of cigarette (regular or menthol) for the duration of the trial
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Plasma Cotinine Concentration | Measured at the end of the last 3 weeks of randomization trial phase | Plasma cotinine is a measure of daily nicotine exposure. Samples were measured in ng/mL. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Quick Inventory of Depressive Symptomatology | Measured at the end of the last 3 weeks of randomization trial phase | A 16-item scale on depression symptoms. The scale range is 0-27 where 0 = Least Severe and 27 = Most Severe. |
| Perceived Stress Scale | Measured at the end of the last 3 weeks of randomization trial phase | 10-item questionnaire measuring the degree to which life situations are appraised stressful. Scale range is 0-40. Higher scores indicate more stress. |
| Minnesota Nicotine Withdrawal Scale | Measured at the end of the last 3 weeks of randomization trial phase | This 8-item scale measures nicotine withdrawal symptoms and the scale range is from 0-32. Higher scores indicate higher severity. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Intention to Quit Smoking | At end of 18-week randomized trial phase | Smokers assigned to the reduced nicotine content cigarette group may have lower perceived dependence and be more likely to report intention to quit smoking |
| Abstinence From Smoking | Follow-up appointment 30 weeks after randomization (12 weeks after last visit of randomized trial phase). | Smokers assigned to reduced nicotine content cigarettes will be more likely to successfully abstain from smoking at the end of the trial, based on all randomized participants, defined as no cigarette use in past 7 days, verified by exhaled carbon monoxide \<10ppm. |
Countries
United States
Participant flow
Pre-assignment details
27 participants attended Visit 1 and consented but did not meet final eligibility criteria. The remaining participants (n=218) began a baseline phase during which 30 participants were lost to follow up or withdrawn from the study before being randomized to the study intervention. 188 participants were randomized into an intervention.
Participants by arm
| Arm | Count |
|---|---|
| Reduced Nicotine Content Cigarettes The experimental group will smoke cigarettes with gradually Reduced Nicotine Content (11.6, 7.4, 3.3, 1.4, 0.7 and 0.2 mg per cigarette) cigarettes, with each nicotine level smoked for 3 weeks, except the lowest level which continues for 6 weeks
Reduced Nicotine Content Cigarettes: Research cigarettes will have gradually reduced nicotine content | 94 |
| Usual Nicotine Content Cigarettes Research cigarettes with a nicotine content similar to participant's usual brand of cigarettes (around 11.6mg)
Usual Nicotine Content Cigarettes: Usual Nicotine Content Cigarettes | 94 |
| Total | 188 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 3 | 5 |
| Overall Study | Lost to Follow-up | 14 | 9 |
| Overall Study | Protocol Violation | 3 | 4 |
| Overall Study | Withdrawal by Subject | 5 | 2 |
Baseline characteristics
| Characteristic | Usual Nicotine Content Cigarettes | Total | Reduced Nicotine Content Cigarettes |
|---|---|---|---|
| Age, Continuous | 43.1 years STANDARD_DEVIATION 13.3 | 43.2 years STANDARD_DEVIATION 12.5 | 43.3 years STANDARD_DEVIATION 11.7 |
| Cigarettes per day | 21.6 cigarettes STANDARD_DEVIATION 10.6 | 20.9 cigarettes STANDARD_DEVIATION 10.7 | 20.2 cigarettes STANDARD_DEVIATION 10.7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 8 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 93 Participants | 180 Participants | 87 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Exhaled Carbon Monoxide | 29.1 parts per million STANDARD_DEVIATION 15.1 | 29.3 parts per million STANDARD_DEVIATION 16.4 | 29.4 parts per million STANDARD_DEVIATION 17.7 |
| Kessler-6 Scale | 6.5 units on a scale STANDARD_DEVIATION 5.1 | 6.1 units on a scale STANDARD_DEVIATION 5.3 | 5.6 units on a scale STANDARD_DEVIATION 5.4 |
| Menthol smoker | 36 Participants | 74 Participants | 38 Participants |
| Minnesota Nicotine Withdrawal Scale | 10.5 units on a scale STANDARD_DEVIATION 6.3 | 10.2 units on a scale STANDARD_DEVIATION 6.8 | 9.9 units on a scale STANDARD_DEVIATION 7.3 |
| Overall Anxiety Severity and Impairment Scale | 5.7 units on a scale STANDARD_DEVIATION 4.3 | 5.3 units on a scale STANDARD_DEVIATION 4.2 | 4.9 units on a scale STANDARD_DEVIATION 4.1 |
| Perceived Stress Scale | 17.1 units on a scale STANDARD_DEVIATION 8.2 | 16.5 units on a scale STANDARD_DEVIATION 7.9 | 16.0 units on a scale STANDARD_DEVIATION 7.5 |
| Plasma Cotinine | 255.9 ng/mL STANDARD_DEVIATION 145.5 | 250.9 ng/mL STANDARD_DEVIATION 141.2 | 245.7 ng/mL STANDARD_DEVIATION 137.2 |
| Quick Inventory of Depressive Symptomatology | 6.3 units on a scale STANDARD_DEVIATION 4.3 | 5.9 units on a scale STANDARD_DEVIATION 4.5 | 5.5 units on a scale STANDARD_DEVIATION 4.8 |
| Race/Ethnicity, Customized African American/black | 11 Participants | 26 Participants | 15 Participants |
| Race/Ethnicity, Customized American Indian/Alaskan native | 1 Participants | 3 Participants | 2 Participants |
| Race/Ethnicity, Customized Asian | 1 Participants | 2 Participants | 1 Participants |
| Race/Ethnicity, Customized Caucasian/white | 76 Participants | 146 Participants | 70 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Pacific Island | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Other | 5 Participants | 11 Participants | 6 Participants |
| Region of Enrollment United States | 94 participants | 188 participants | 94 participants |
| Sex: Female, Male Female | 54 Participants | 114 Participants | 60 Participants |
| Sex: Female, Male Male | 40 Participants | 74 Participants | 34 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 94 | 0 / 94 |
| other Total, other adverse events | 70 / 94 | 72 / 94 |
| serious Total, serious adverse events | 7 / 94 | 10 / 94 |
Outcome results
Primary
Plasma Cotinine Concentration
Plasma cotinine is a measure of daily nicotine exposure. Samples were measured in ng/mL.
Time frame: Measured at the end of the last 3 weeks of randomization trial phase
Population: Randomized trial phase completers with non-missing values for the outcome at both time points being used in the regression (complete case analysis).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Reduced Nicotine Content Cigarettes | Plasma Cotinine Concentration | 82.8 ng/mL | Standard Deviation 154.3 |
| Usual Nicotine Content Cigarettes | Plasma Cotinine Concentration | 259.0 ng/mL | Standard Deviation 151.3 |
p-value: <0.000195% CI: [-218.3, -133.1]Regression, Linear
Secondary
Minnesota Nicotine Withdrawal Scale
This 8-item scale measures nicotine withdrawal symptoms and the scale range is from 0-32. Higher scores indicate higher severity.
Time frame: Measured at the end of the last 3 weeks of randomization trial phase
Population: Randomized trial phase completers with non-missing values for the outcome at both time points being used in the regression (complete case analysis).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Reduced Nicotine Content Cigarettes | Minnesota Nicotine Withdrawal Scale | 8.1 score on a scale | Standard Deviation 6.8 |
| Usual Nicotine Content Cigarettes | Minnesota Nicotine Withdrawal Scale | 9.0 score on a scale | Standard Deviation 5.9 |
p-value: 0.6595% CI: [-1.68, 1.05]Regression, Linear
Secondary
Perceived Stress Scale
10-item questionnaire measuring the degree to which life situations are appraised stressful. Scale range is 0-40. Higher scores indicate more stress.
Time frame: Measured at the end of the last 3 weeks of randomization trial phase
Population: Randomized trial phase completers with non-missing values for the outcome at both time points being used in the regression (complete case analysis).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Reduced Nicotine Content Cigarettes | Perceived Stress Scale | 15.0 score on a scale | Standard Deviation 7.6 |
| Usual Nicotine Content Cigarettes | Perceived Stress Scale | 15.1 score on a scale | Standard Deviation 7.8 |
p-value: 0.6795% CI: [-1.4, 2.16]Regression, Linear
Secondary
Quick Inventory of Depressive Symptomatology
A 16-item scale on depression symptoms. The scale range is 0-27 where 0 = Least Severe and 27 = Most Severe.
Time frame: Measured at the end of the last 3 weeks of randomization trial phase
Population: Randomized trial phase completers with non-missing values for the outcome at both time points being used in the regression (complete case analysis).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Reduced Nicotine Content Cigarettes | Quick Inventory of Depressive Symptomatology | 5.5 score on a scale | Standard Deviation 4.3 |
| Usual Nicotine Content Cigarettes | Quick Inventory of Depressive Symptomatology | 5.3 score on a scale | Standard Deviation 3.9 |
p-value: 0.1695% CI: [-0.28, 1.65]Regression, Linear
Other Pre-specified
Abstinence From Smoking
Smokers assigned to reduced nicotine content cigarettes will be more likely to successfully abstain from smoking at the end of the trial, based on all randomized participants, defined as no cigarette use in past 7 days, verified by exhaled carbon monoxide \<10ppm.
Time frame: Follow-up appointment 30 weeks after randomization (12 weeks after last visit of randomized trial phase).
Population: All randomized participants
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Reduced Nicotine Content Cigarettes | Abstinence From Smoking | 17 Participants |
| Usual Nicotine Content Cigarettes | Abstinence From Smoking | 4 Participants |
Other Pre-specified
Intention to Quit Smoking
Smokers assigned to the reduced nicotine content cigarette group may have lower perceived dependence and be more likely to report intention to quit smoking
Time frame: At end of 18-week randomized trial phase
Population: Participants who attended the visit at the end of the 18-week randomized trial phase
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Reduced Nicotine Content Cigarettes | Intention to Quit Smoking | 33 Participants |
| Usual Nicotine Content Cigarettes | Intention to Quit Smoking | 25 Participants |