Nicotine Dependence
Conditions
Brief summary
The objective of the current study is to evaluate the validity of the No Shock, Predictable Shock, Unpredictable Shock (NPU) stressor task for use as a surrogate endpoint to predict short-term clinical outcomes among smokers during a smoking cessation attempt.
Detailed description
Smokers recruited for this study are randomly assigned at a screening session to complete the NPU stressor task pre-quit or post-quit (i.e., nicotine deprived or non-deprived). Participants are also randomized to receive either placebo or active combination nicotine replacement therapy (NRT; patches and lozenges) for a two week smoking cessation period. The NPU stressor task measures stressor reactivity to predictable and unpredictable stressors (i.e., electric shock). Startle potentiation during predictable and unpredictable stressors (relative to no-shock) provides the primary measures of stressor reactivity in this task. Predictable and unpredictable startle potentiation are used to calculate overall stressor reactivity and selective unpredictable stressor reactivity. Further detail on these reactivity measures is provided in the Independent Variables section. Detail on the quantification of startle potentiation is provided at the end of this registration. Smokers provide three weeks (1 week pre-quit, 2 weeks post-quit) of brief 4x daily, real-time web-survey reports of recent cigarette use, NRT use, and other measures not relevant to this study's purpose on the participants' smartphones. At two weeks post-quit, smokers are scheduled for a laboratory visit where participants provide an additional report via staff interview of any smoking during the two-week smoking cessation period. The stressor reactivity measures from the NPU task will be tested as predictors of clinical outcome (i.e., continuous abstinence during the two-week cessation period) to evaluate the validity of each as surrogate endpoints for use in research on stress mechanisms in smoking relapse. Deprivation status at the time of the NPU stressor task will be examined as a moderator of the effect of stressor reactivity to determine if the surrogate endpoints predict clinical outcome generally or only as deprivation increases.
Interventions
COMBINATION_PRODUCTnicotine
OTHERplacebo
Sponsors
University of Wisconsin, Madison
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
HEALTH_SERVICES_RESEARCH
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
* cigarette use over 10 cigarettes/day for over two years; * smoking within the first 30 minutes of waking up * expired air carbon monoxide (CO) level \>6 ppm * self-reported motivation to quit smoking * and an agreement to respond to ecological momentary assessment prompts (via SMS) throughout the day for three weeks.
Exclusion criteria
* Health screening are performed by questionnaire and reviewed by study staff (RA or Research Specialist) to ensure that smokers can safely use the nicotine patch and lozenge. Specifically, smokers will be excluded for FDA contraindications for nicotine replacement therapy (i.e., no uncontrolled hypertension, recent myocardial infarction, diabetes, heart disease, asthma, stomach ulcers). * All women of child-bearing potential will be required to agree to use an approved method of birth control to prevent pregnancy during the course of the study. * All participants will report no medical or psychiatric condition that would contraindicate exposure to electric shock. * Participants with uncorrected auditory or visual problems will be excluded. Additional Data Exclusions 1. As part of the NPU stressor task, smokers are asked to indicate if the participant can be shocked in the next 5 seconds at various points during the task. Responses to these questions are used to verify that the participant understands the cue-shock contingencies. Smokers who answer \< 10 out of 14 questions correctly the NPU stressor task during the experimental session will be excluded from all analyses and replaced. 2. Smokers with 20% of cue trials identified as artifact in the NPU task will be excluded from all analyses and replaced. 3. The analysis will NOT exclude smokers who are startle non-responders given that the use of these surrogate endpoints in practice would likely need to include these individuals to avoid unnecessary data loss. 4. Smokers who do not report a complete abstinence between quit date/time and final laboratory visit (which occurs 12-36 hours later) will be considered to not have quit and will be excluded from all analyses and replaced. 5. Smokers for whom the investigators cannot definitively quantify an outcome with respect to continuous abstinence will be excluded from all analyses and replaced. Any report of smoking during the two-week cessation period (reported either during the 4x daily web surveys or the laboratory visit at 2 weeks) is sufficient to code the smoker to have lapsed (i.e., not continuously abstinent), even if the participants do not complete the full two weeks of web surveys and/or the 2-week laboratory visit. However, the status of smokers who report no smoking during the cessation attempt but have both a high level of missing data from the web surveys (\> 25% of reports) and no two-week laboratory visit report will be deemed uncertain. These smokers will be excluded and replaced. 6. The investigators will conduct case analyses to identify participants who are model outliers with Bonferroni-corrected studentized residuals p \< 0.05. These model outliers will be excluded but NOT replaced (because the participants are not identified until after data collection has been completed).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Stressor Reactivity | up to 24 hours after start of cessation attempt (deprived groups); during normal smoking prior to quit attempt, ie. Baseline (non-deprived groups) | The average of unpredictable startle potentiation and predictable startle potentiation during the first administration of the NPU stressor task. |
| Relative Unpredictable Stressor Reactivity | up to 24 hours post cessation attempt (deprived groups); during normal smoking prior to quit attempt, ie. Baseline (non-deprived groups) | Unpredictable startle potentiation minus predictable startle potentiation during the first administration of the NPU stressor task |
| Change in Overall Stressor Reactivity | baseline and up to 14 days post cessation attempt (non-deprived groups); baseline and up to 24 hours post quit attempt (deprived groups) | A difference score of overall stressor reactivity during the second administration of the NPU stressor task relative to the first NPU stressor task |
| Change in Relative Unpredictable Stressor Reactivity | baseline and up to 14 days post cessation attempt (non-deprived groups); baseline and up to 24 hours post quit attempt (deprived groups) | A difference score of relative unpredictable stressor reactivity during the second administration of the NPU stressor task relative to the first NPU stressor task |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Active Deprived 21 mg nicotine patches and 2 mg nicotine lozenges
\+ First NPU task takes place 24 hours after start of quit attempt | 35 |
| Active Non-Deprived 21 mg nicotine patches and 2 mg nicotine lozenges
\+ First NPU task takes place during normal smoking prior to quit attempt | 32 |
| Placebo Deprived Placebo patches and placebo lozenges
\+ First NPU task takes place 24 hours after start of quit attempt | 34 |
| Placebo Non-Deprived Placebo patches and placebo lozenges
\+ First NPU task takes place during normal smoking prior to quit attempt | 32 |
| Total | 133 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | data collection artifact | 0 | 1 | 0 | 0 |
| Overall Study | Declined due to shock | 1 | 2 | 2 | 3 |
| Overall Study | Protocol Violation | 5 | 10 | 2 | 13 |
| Overall Study | Withdrawal by Subject | 12 | 8 | 21 | 13 |
Baseline characteristics
| Characteristic | Active Deprived | Total | Placebo Non-Deprived | Placebo Deprived | Active Non-Deprived |
|---|---|---|---|---|---|
| Age, Continuous | 38.1 years STANDARD_DEVIATION 10.7 | 40 years STANDARD_DEVIATION 11.65 | 42 years STANDARD_DEVIATION 11.3 | 40.6 years STANDARD_DEVIATION 12.3 | 39.7 years STANDARD_DEVIATION 12.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 2 Participants | 0 Participants | 1 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 34 Participants | 131 Participants | 32 Participants | 33 Participants | 32 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 3 Participants | 1 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 01 Participants |
| Race (NIH/OMB) Black or African American | 9 Participants | 36 Participants | 9 Participants | 11 Participants | 7 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 4 Participants | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 26 Participants | 89 Participants | 21 Participants | 21 Participants | 21 Participants |
| Region of Enrollment United States | 35 participants | 133 participants | 32 participants | 34 participants | 32 participants |
| Sex: Female, Male Female | 14 Participants | 50 Participants | 11 Participants | 12 Participants | 13 Participants |
| Sex: Female, Male Male | 21 Participants | 83 Participants | 21 Participants | 22 Participants | 19 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 35 | 0 / 32 | 0 / 34 | 0 / 32 |
| other Total, other adverse events | 0 / 35 | 0 / 32 | 0 / 34 | 0 / 32 |
| serious Total, serious adverse events | 0 / 35 | 0 / 32 | 0 / 34 | 0 / 32 |
Outcome results
Primary
Change in Overall Stressor Reactivity
A difference score of overall stressor reactivity during the second administration of the NPU stressor task relative to the first NPU stressor task
Time frame: baseline and up to 14 days post cessation attempt (non-deprived groups); baseline and up to 24 hours post quit attempt (deprived groups)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active Deprived | Change in Overall Stressor Reactivity | -2.94 change in microvolts | Standard Deviation 16.3 |
| Active Non-deprived | Change in Overall Stressor Reactivity | 0.929 change in microvolts | Standard Deviation 13 |
| Placebo Deprived | Change in Overall Stressor Reactivity | -10.3 change in microvolts | Standard Deviation 24 |
| Placebo Non-deprived | Change in Overall Stressor Reactivity | 4.78 change in microvolts | Standard Deviation 13.6 |
Primary
Change in Relative Unpredictable Stressor Reactivity
A difference score of relative unpredictable stressor reactivity during the second administration of the NPU stressor task relative to the first NPU stressor task
Time frame: baseline and up to 14 days post cessation attempt (non-deprived groups); baseline and up to 24 hours post quit attempt (deprived groups)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active Deprived | Change in Relative Unpredictable Stressor Reactivity | 1.95 change in microvolts | Standard Deviation 15.5 |
| Active Non-deprived | Change in Relative Unpredictable Stressor Reactivity | 3.99 change in microvolts | Standard Deviation 14.8 |
| Placebo Deprived | Change in Relative Unpredictable Stressor Reactivity | 0.889 change in microvolts | Standard Deviation 16 |
| Placebo Non-deprived | Change in Relative Unpredictable Stressor Reactivity | -1.35 change in microvolts | Standard Deviation 11.3 |
Primary
Overall Stressor Reactivity
The average of unpredictable startle potentiation and predictable startle potentiation during the first administration of the NPU stressor task.
Time frame: up to 24 hours after start of cessation attempt (deprived groups); during normal smoking prior to quit attempt, ie. Baseline (non-deprived groups)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active Deprived | Overall Stressor Reactivity | 25.1 microvolts | Standard Deviation 23 |
| Active Non-deprived | Overall Stressor Reactivity | 22.5 microvolts | Standard Deviation 24.4 |
| Placebo Deprived | Overall Stressor Reactivity | 32.3 microvolts | Standard Deviation 29.6 |
| Placebo Non-deprived | Overall Stressor Reactivity | 16.9 microvolts | Standard Deviation 17.7 |
Primary
Relative Unpredictable Stressor Reactivity
Unpredictable startle potentiation minus predictable startle potentiation during the first administration of the NPU stressor task
Time frame: up to 24 hours post cessation attempt (deprived groups); during normal smoking prior to quit attempt, ie. Baseline (non-deprived groups)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active Deprived | Relative Unpredictable Stressor Reactivity | -6.77 microvolts | Standard Deviation 14 |
| Active Non-deprived | Relative Unpredictable Stressor Reactivity | -7.91 microvolts | Standard Deviation 14.4 |
| Placebo Deprived | Relative Unpredictable Stressor Reactivity | -6.06 microvolts | Standard Deviation 12.3 |
| Placebo Non-deprived | Relative Unpredictable Stressor Reactivity | -4.99 microvolts | Standard Deviation 14 |