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Stress Neuroadaptation in Tobacco Dependence

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ClinicalTrials.gov Identifier: NCT03262233
Recruitment Status : Completed
First Posted : August 25, 2017
Results First Posted : April 23, 2019
Last Update Posted : April 23, 2019
Sponsor:
Information provided by (Responsible Party):
University of Wisconsin, Madison

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.

Condition or disease Intervention/treatment Phase
Nicotine Dependence Combination Product: nicotine Other: placebo Phase 4

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.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 226 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Participant)
Primary Purpose: Health Services Research
Official Title: Clinical Relevance of Stress Neuroadaptation in Tobacco Dependence
Actual Study Start Date : April 1, 2015
Actual Primary Completion Date : February 20, 2018
Actual Study Completion Date : February 20, 2018

Arm Intervention/treatment
Experimental: Active Deprived

21 mg nicotine patches and 2 mg nicotine lozenges

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

Combination Product: nicotine
Experimental: Active Non-deprived

21 mg nicotine patches and 2 mg nicotine lozenges

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

Combination Product: nicotine
Active Comparator: Placebo Deprived

Placebo patches and placebo lozenges

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

Other: placebo
Active Comparator: Placebo Non-deprived

Placebo patches and placebo lozenges

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

Other: placebo



Primary Outcome Measures :
  1. Overall Stressor Reactivity [ 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) ]
    The average of unpredictable startle potentiation and predictable startle potentiation during the first administration of the NPU stressor task.

  2. Relative Unpredictable Stressor Reactivity [ Time Frame: 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

  3. Change in Overall Stressor Reactivity [ 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) ]
    A difference score of overall stressor reactivity during the second administration of the NPU stressor task relative to the first NPU stressor task

  4. Change in Relative Unpredictable Stressor Reactivity [ 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) ]
    A difference score of relative unpredictable stressor reactivity during the second administration of the NPU stressor task relative to the first NPU stressor task



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03262233


Locations
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United States, Wisconsin
University of Wisconsin
Madison, Wisconsin, United States, 53706
Sponsors and Collaborators
University of Wisconsin, Madison
  Study Documents (Full-Text)

Documents provided by University of Wisconsin, Madison:

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Responsible Party: University of Wisconsin, Madison
ClinicalTrials.gov Identifier: NCT03262233     History of Changes
Other Study ID Numbers: 2017-0433
First Posted: August 25, 2017    Key Record Dates
Results First Posted: April 23, 2019
Last Update Posted: April 23, 2019
Last Verified: April 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: IPD will be shared on the data repository at Open Science Foundation
Supporting Materials: Study Protocol
Analytic Code
Time Frame: Data will be available on submission of first manuscript based on study
Access Criteria: Data are completely open
URL: https://osf.io/dz9yu/

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
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Tobacco Use Disorder
Substance-Related Disorders
Chemically-Induced Disorders
Mental Disorders
Nicotine
Ganglionic Stimulants
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Nicotinic Agonists
Cholinergic Agonists
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action