Stress Neuroadaptation in Tobacco Dependence

NCT ID: NCT03262233

Last Updated: 2019-04-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 226 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-04-01
• Study Completion Date: 2018-02-20

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.

Conditions

Nicotine Dependence

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: HEALTH_SERVICES_RESEARCH
• Blinding Strategy: SINGLE

Study Groups

Active Deprived

21 mg nicotine patches and 2 mg nicotine lozenges

+ First NPU task takes place 24 hours after start of quit attempt

Group Type: EXPERIMENTAL

nicotine

Intervention Type: COMBINATION_PRODUCT

Active Non-deprived

21 mg nicotine patches and 2 mg nicotine lozenges

+ First NPU task takes place during normal smoking prior to quit attempt

Group Type: EXPERIMENTAL

nicotine

Intervention Type: COMBINATION_PRODUCT

Placebo Deprived

Placebo patches and placebo lozenges

+ First NPU task takes place 24 hours after start of quit attempt

Group Type: ACTIVE_COMPARATOR

placebo

Intervention Type: OTHER

Placebo Non-deprived

Placebo patches and placebo lozenges

+ First NPU task takes place during normal smoking prior to quit attempt

Group Type: ACTIVE_COMPARATOR

placebo

Intervention Type: OTHER

Interventions

nicotine

Intervention Type: COMBINATION_PRODUCT

placebo

Intervention Type: OTHER

Eligibility Criteria

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).

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Wisconsin, Madison

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

University of Wisconsin

Madison, Wisconsin, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

2017-0433

Identifier Type: -

Identifier Source: org_study_id