Nicotine DependencePhase 4NCT03262233
Stress Neuroadaptation in Tobacco Dependence
A Phase 4 study testing nicotine in people with Nicotine Dependence, run by University of Wisconsin, Madison at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Nicotine Dependence
- What is being tested?
- nicotine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 226 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Apr 2015to 20 Feb 2018
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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.
Who cannot join
- 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
- 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.
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- 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).
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Clinical Relevance of Stress Neuroadaptation in Tobacco Dependence
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.
Read the 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
- Being tested
- nicotine, placebo
- Medical subject headings
- Tobacco Use Disorder
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
nicotineCombination product
placeboOther
| Study group | Role | What they receive |
|---|---|---|
| Active Deprived | Experimental | 21 mg nicotine patches and 2 mg nicotine lozenges
+ First NPU task takes place 24 hours after start of quit attempt Receives: 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 Receives: Combination Product: nicotine |
| Placebo Deprived | Active comparator | Placebo patches and placebo lozenges
+ First NPU task takes place 24 hours after start of quit attempt Receives: Other: placebo |
| Placebo Non-deprived | Active comparator | Placebo patches and placebo lozenges
+ First NPU task takes place during normal smoking prior to quit attempt Receives: Other: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Stressor Reactivity
The average of unpredictable startle potentiation and predictable startle potentiation during the first administration of the NPU stressor task.
Measured: 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
Measured: 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
Measured: 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
Measured: baseline and up to 14 days post cessation attempt (non-deprived groups); baseline and up to 24 hours post quit attempt (deprived groups)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Aug 2017
- Study start1 Apr 2015
- Primary completion20 Feb 2018
- Study completion20 Feb 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Nicotine DependenceStudies of the same condition, open and under way.
- More trials run by University of Wisconsin, MadisonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Health services research
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 226 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Wisconsin, Madison
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03262233
- Sponsor's protocol ID
- 2017-0433
- Status last verified
- Apr 2019
- First submitted
- 23 Aug 2017
- Last updated
- 23 Apr 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: IPD will be shared on the data repository at Open Science Foundation
Study at a glance
From the registry record, last updated by the sponsor on 23 Apr 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clinical Relevance of Stress Neuroadaptation in Tobacco Dependence
- ClinicalTrials.gov ID
- NCT03262233
- Acronym / sponsor ID
- 2017-0433
- Conditions
- Nicotine Dependence
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 226 participants (actual)
- Lead sponsor
- University of Wisconsin, MadisonUniversity, hospital or other
- Study start
- 1 Apr 2015 (actual)
- Primary completion
- 20 Feb 2018 (actual)
- Study completion
- 20 Feb 2018 (actual)
- First posted
- 25 Aug 2017 (actual)
- Results
- Posted 23 Apr 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Health services research
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Active Deprived | Experimental | Combination Product: nicotine21 mg nicotine patches and 2 mg nicotine lozenges + First NPU task takes place 24 hours after start of quit attempt |
| Active Non-deprived | Experimental | Combination Product: nicotine21 mg nicotine patches and 2 mg nicotine lozenges + First NPU task takes place during normal smoking prior to quit attempt |
| Placebo Deprived | Active comparator | Other: placeboPlacebo patches and placebo lozenges + First NPU task takes place 24 hours after start of quit attempt |
| Placebo Non-deprived | Active comparator | Other: placeboPlacebo patches and placebo lozenges + First NPU task takes place during normal smoking prior to quit attempt |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (11 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| nicotine | Combination product | Active Deprived, Active Non-deprived |
| placebo | Other | Placebo Deprived, Placebo Non-deprived |
Primary outcome
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.
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
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
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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Apr 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes. IPD will be shared on the data repository at Open Science Foundation
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing nicotine in people with Nicotine Dependence, run by University of Wisconsin, Madison at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 23 Apr 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 23 Apr 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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 study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Apr 2019.