Stress Neuroadaptation in Tobacco Dependence

NCT03262233 | Completed Phase 4 Results FDA Drug

• 1 other identifier: 2017-0433
• Study Type: interventional
• Target: 226
• Locations: 1 country
• Sites: 1

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.

Conditions

Nicotine Dependence

Outcome Measures

Primary Outcomes (4)

• Overall Stressor Reactivity

  The average of unpredictable startle potentiation and predictable startle potentiation during the first administration of the NPU stressor task.

  up to 24 hours after start of cessation attempt (deprived groups); during normal smoking prior to quit attempt, ie. Baseline (non-deprived groups)

• Relative Unpredictable Stressor Reactivity

  Unpredictable startle potentiation minus predictable startle potentiation during the first administration of the NPU stressor task

  up to 24 hours post cessation attempt (deprived groups); during normal smoking prior to quit attempt, ie. Baseline (non-deprived groups)

• 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

  baseline and up to 14 days post cessation attempt (non-deprived groups); baseline and up to 24 hours post quit attempt (deprived groups)

• 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

  baseline and up to 14 days post cessation attempt (non-deprived groups); baseline and up to 24 hours post quit attempt (deprived groups)

Study Arms (4)

Active Deprived

EXPERIMENTAL

21 mg nicotine patches and 2 mg nicotine lozenges \+ First NPU task takes place 24 hours after start of quit attempt

Combination Product: nicotine

Active Non-deprived

EXPERIMENTAL

21 mg nicotine patches and 2 mg nicotine lozenges \+ First NPU task takes place during normal smoking prior to quit attempt

Combination Product: nicotine

Placebo Deprived

ACTIVE COMPARATOR

Placebo patches and placebo lozenges \+ First NPU task takes place 24 hours after start of quit attempt

Other: placebo

Placebo Non-deprived

ACTIVE COMPARATOR

Placebo patches and placebo lozenges \+ First NPU task takes place during normal smoking prior to quit attempt

Other: placebo

Interventions

nicotine COMBINATION_PRODUCT

Active Deprived; Active Non-deprived

placebo OTHER

Placebo Deprived; Placebo Non-deprived

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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.
• Smokers with 20% of cue trials identified as artifact in the NPU task will be excluded from all analyses and replaced.
• 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.
• 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.
• 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.
• 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).

Sponsors & Collaborators

• University of Wisconsin, Madison: lead

Study Sites (1)

University of Wisconsin

Madison, Wisconsin, 53706, United States

Location

MeSH Terms

Conditions

Tobacco Use Disorder

Interventions

Nicotine

Condition Hierarchy (Ancestors)

Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Solanaceous Alkaloids; Alkaloids; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring

Results Point of Contact

• Title: John Curtin
• Organization: UW-Madison

jjcurtin@wisc.edu

608-262-0387

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: HEALTH SERVICES RESEARCH
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 23, 2017
• First Posted: August 25, 2017
• Study Start: April 1, 2015
• Primary Completion: February 20, 2018
• Study Completion: February 20, 2018
• Last Updated: April 23, 2019
• Results First Posted: April 23, 2019

Record last verified: 2019-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ANALYTIC CODE
• Time Frame: Data will be available on submission of first manuscript based on study
• Access Criteria: Data are completely open

Locations

US (1)