SmokingPhase 1NNNNCT01056926
Neurobiology of Nicotine and Non-nicotine Components of Tobacco Addiction
A Phase 1 study testing Quit smoking and Nicotine patch in people with Smoking, run by Duke University at 1 site in United States.
Trial summary
In the present study the investigators will measure the effects of nicotine and non-nicotine factors on brain function during cognitive processes that are differentially sensitive to these factors. Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Smoking
- What is being tested?
- Quit smoking and Nicotine patch
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 147 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2009to Nov 2011
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- generally healthy,
- between the ages of 18 and 55,
- smoking of at least 10 cigarettes/day of a brand delivering > 0.5 mg nicotine according to the standard Federal Trade Commission (FTC) method,
- an afternoon expired carbon monoxide concentration of at least 10 ppm (to confirm inhalation),
- no interest in quitting smoking as measured by self-report, and
- right-handed as measured by a three-item scale used in our laboratory.
Who cannot join
- inability to attend all required experimental sessions,
- significant health problems (e.g., chronic hypertension, emphysema, seizure disorder, history of significant heart problems),
- use of psychoactive medications,
- use of smokeless tobacco,
- current alcohol or drug abuse,
- use of illegal drugs as measured by urine drug screen,
Show all 9Show fewer
- current use of nicotine replacement therapy or other smoking cessation treatment,
- presence of conditions that would make MRI unsafe (e.g., pacemaker),
- presence of conditions contraindicated for nicotine replacement therapy (e.g., skin allergies or disorders).
Trial locations and contacts
1 site in 1 country.
United States1 site
Duke University Medical Center
Durham, North Carolina, 27705
About this study
In the present study the investigators will measure the effects of nicotine and non-nicotine factors on brain function during cognitive processes that are differentially sensitive to these factors. One process-continuous working memory (CWM)-is implemented via a network of frontal and parietal brain regions and is highly dopamine dependent. Smoking cessation results in significant deficits in CWM which can persist for weeks and are reversed by resumption of nicotine administration in the form of smoking or nicotine replacement. Additionally, CWM deficits are observed during smoking of denic cigarettes. Brain function during CWM is modulated by smoking abstinence and subsequent nicotine administration and activity in the dlPFC is implicated in these effects. Collectively, these data suggest that CWM is highly sensitive to the nicotine, but not non-nicotine components of smoking. Brain function during CWM is altered by smoking abstinence and nicotine, but the effect of smoking, in the absence of nicotine, has not been evaluated.
Another process-cue-reactivity (CR)-results from the repeated pairing of otherwise neutral stimuli with nicotine administration. Acute smoking cessation has not been shown to have strong effects on CR in the form of cue-provoked craving, nor has nicotine replacement been shown to have robust effects on CR. Likewise, the direct effects of smoking abstinence on brain CR have been small; though craving has been shown to modulate relations between abstinence and CR. Moreover, recent data from our lab suggest larger 'doses' of abstinence (~ 24 hrs) may amplify brain responses to cues. The effect of smoking in the absence of nicotine, on CR has not, to our knowledge, been evaluated. Collectively, these data suggest that CR in the form of cue-induced craving is not highly sensitive to the effects of short-term smoking abstinence or nicotine. Brain CR is modulated by abstinence-induced craving and longer-term abstinence, but it is unclear whether abstinence from nicotine or non-nicotine components is responsible for these effects.
In the present study, we propose to evaluate the effects of non-nicotine and nicotine factors on CWM and CR using functional magnetic resonance imaging. This method allows for the non-invasive assessment of brain function. We will also examine the role of genes in moderating and mediating the effects of nicotine and non-nicotine factors on cognitive function
Read the detailed description
Overview. In a fully factorial design, thirty-six (n=36) adult smokers will undergo fMRI scanning at least 24 hours after each of the following conditions: 1) Nicotine Patch + Denic Smoking, 2) Placebo Patch + Denic Smoking, 3) Nicotine Patch + No Smoking, and 4) Placebo Patch+ No Smoking. During scanning, participants will complete a laboratory based measure of continuous working memory (n-back)-a measure of continuous working memory-and the cue-reactivity task (CR)-a measure of responses to smoking cues. Broadly, we hypothesize 1) abstinence from nicotine, regardless of smoking, will disrupt CWM performance and brain function, 2) abstinence from nicotine and denics will potentiate brain CR but differentially contribute to this effect and 3) that individual differences in smoking behavior and motivation will predict the effects of nicotine and non-nicotine factors on brain function.
- Conditions
- Smoking
- Being tested
- Quit smoking, Nicotine patch, Placebo Patch
- Keywords
- smoking, nicotine, Effects of nicotine and non-nicotine factors on continuous working memory., Effects of nicotine and non-nicotine factors on cue reactivity., Use of nicotine patches, placebo patches, and denicotinized cigarettes., memory
- Medical subject headings
- Smoking
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Quit smokingBehavioural
Subjects will quit smoking for 2 fMRIs, each abstinence lasting 2 days
Nicotine patchDrug
Subjects will wear a 21mg patch for 2 fMRIs, each condition lasting 2 days. They will take the patch off at night.
Placebo PatchDrug
Subjects will wear a placebo patch for 2 fMRIs, each condition lasting 2 days. They will take the patch off at night.
| Study group | Role | What they receive |
|---|---|---|
| Nicotine Patch + Denic Smoking | Experimental | Subjects will wear a nicotine patch and smoke denic cigarettes for 24 hours prior to scan Receives: Drug: Nicotine patch |
| Placebo Patch + Denic Smoking | Experimental | Subjects will wear a placebo patch and smoke denic cigarettes 24 hours prior to scan Receives: Drug: Placebo Patch |
| Nicotine Patch + No Smoking | Experimental | Subjects will wear a nicotine patch and not smoke for 24 hours prior to scan Receives: Behavioral: Quit smoking; Drug: Nicotine patch |
| Placebo Patch + No Smoking | Experimental | Subjects will wear a placebo patch and not smoke for 24 hours prior to scan Receives: Behavioral: Quit smoking; Drug: Placebo Patch |
What is being measured
The primary outcome is the main question the study is designed to answer.
Measure cue reactivity while subjects undergo a functional magnetic resonance imaging (fMRI).
Measured: 1.25 hours
Secondary outcomes (1)
Measure continuous working memory while subjects are scanned in a functional magnetic resonance imaging (fMRI).
Measured: 1.25 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jan 2010 (estimated)
- Study startMar 2009
- Primary completionNov 2011
- Study completionNov 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for SmokingStudies of the same condition, open and under way.
- More trials run by Duke UniversityThe 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 1
- Primary purpose
- Health services research
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 147 participants (actual)
Sponsor and investigators
- Lead sponsor
- Duke University
- Sponsor type
- University, hospital or other
- Collaborators
- National Institutes of Health (NIH)
- Responsible party
- Sponsor
- Investigators
- Joseph McClernon, Ph.D, Principal investigator, Duke University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01056926
- Sponsor's protocol ID
- Pro00004092
- Acronym
- NNN
- Status last verified
- Jul 2013
- First submitted
- 14 Jan 2010
- Last updated
- 31 Jan 2017
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 31 Jan 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Neurobiology of Nicotine and Non-nicotine Components of Tobacco Addiction
- ClinicalTrials.gov ID
- NCT01056926
- Acronym / sponsor ID
- NNN / Pro00004092
- Conditions
- Smoking
- Keywords
- smoking, nicotine, Effects of nicotine and non-nicotine factors on continuous working memory., Effects of nicotine and non-nicotine factors on cue reactivity., Use of nicotine patches, placebo patches, and denicotinized cigarettes., memory
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 147 participants (actual)
- Lead sponsor
- Duke UniversityUniversity, hospital or other
- Collaborators
- National Institutes of Health (NIH)
- Study start
- Mar 2009
- Primary completion
- Nov 2011 (actual)
- Study completion
- Nov 2011 (actual)
- First posted
- 26 Jan 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
In the present study the investigators will measure the effects of nicotine and non-nicotine factors on brain function during cognitive processes that are differentially sensitive to these factors. One process-continuous working memory (CWM)-is implemented via a network of frontal and parietal brain regions and is highly dopamine dependent. Smoking cessation results in significant deficits in CWM which can persist for weeks and are reversed by resumption of nicotine administration in the form of smoking or nicotine replacement. Additionally, CWM deficits are observed during smoking of denic cigarettes. Brain function during CWM is modulated by smoking abstinence and subsequent nicotine administration and activity in the dlPFC is implicated in these effects. Collectively, these data suggest that CWM is highly sensitive to the nicotine, but not non-nicotine components of smoking. Brain function during CWM is altered by smoking abstinence and nicotine, but the effect of smoking, in the absence of nicotine, has not been evaluated.
Another process-cue-reactivity (CR)-results from the repeated pairing of otherwise neutral stimuli with nicotine administration. Acute smoking cessation has not been shown to have strong effects on CR in the form of cue-provoked craving, nor has nicotine replacement been shown to have robust effects on CR. Likewise, the direct effects of smoking abstinence on brain CR have been small; though craving has been shown to modulate relations between abstinence and CR. Moreover, recent data from our lab suggest larger 'doses' of abstinence (~ 24 hrs) may amplify brain responses to cues. The effect of smoking in the absence of nicotine, on CR has not, to our knowledge, been evaluated. Collectively, these data suggest that CR in the form of cue-induced craving is not highly sensitive to the effects of short-term smoking abstinence or nicotine. Brain CR is modulated by abstinence-induced craving and longer-term abstinence, but it is unclear whether abstinence from nicotine or non-nicotine components is responsible for these effects.
In the present study, we propose to evaluate the effects of non-nicotine and nicotine factors on CWM and CR using functional magnetic resonance imaging. This method allows for the non-invasive assessment of brain function. We will also examine the role of genes in moderating and mediating the effects of nicotine and non-nicotine factors on cognitive function
Detailed description
Overview. In a fully factorial design, thirty-six (n=36) adult smokers will undergo fMRI scanning at least 24 hours after each of the following conditions: 1) Nicotine Patch + Denic Smoking, 2) Placebo Patch + Denic Smoking, 3) Nicotine Patch + No Smoking, and 4) Placebo Patch+ No Smoking. During scanning, participants will complete a laboratory based measure of continuous working memory (n-back)-a measure of continuous working memory-and the cue-reactivity task (CR)-a measure of responses to smoking cues. Broadly, we hypothesize 1) abstinence from nicotine, regardless of smoking, will disrupt CWM performance and brain function, 2) abstinence from nicotine and denics will potentiate brain CR but differentially contribute to this effect and 3) that individual differences in smoking behavior and motivation will predict the effects of nicotine and non-nicotine factors on brain function.
Study design
- Primary purpose
- Health services research
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Double blind (participant, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Nicotine Patch + Denic Smoking | Experimental | Drug: Nicotine patchSubjects will wear a nicotine patch and smoke denic cigarettes for 24 hours prior to scan |
| Placebo Patch + Denic Smoking | Experimental | Drug: Placebo PatchSubjects will wear a placebo patch and smoke denic cigarettes 24 hours prior to scan |
| Nicotine Patch + No Smoking | Experimental | Behavioral: Quit smoking, Drug: Nicotine patchSubjects will wear a nicotine patch and not smoke for 24 hours prior to scan |
| Placebo Patch + No Smoking | Experimental | Behavioral: Quit smoking, Drug: Placebo PatchSubjects will wear a placebo patch and not smoke for 24 hours prior to scan |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- generally healthy,
- between the ages of 18 and 55,
- smoking of at least 10 cigarettes/day of a brand delivering > 0.5 mg nicotine according to the standard Federal Trade Commission (FTC) method,
- an afternoon expired carbon monoxide concentration of at least 10 ppm (to confirm inhalation),
- no interest in quitting smoking as measured by self-report, and
Key exclusion criteria (9 listed)
- inability to attend all required experimental sessions,
- significant health problems (e.g., chronic hypertension, emphysema, seizure disorder, history of significant heart problems),
- use of psychoactive medications,
- use of smokeless tobacco,
- current alcohol or drug abuse,
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 |
|---|---|---|
| Quit smokingSubjects will quit smoking for 2 fMRIs, each abstinence lasting 2 days | Behavioural | Nicotine Patch + No Smoking, Placebo Patch + No Smoking |
| Nicotine patchSubjects will wear a 21mg patch for 2 fMRIs, each condition lasting 2 days. They will take the patch off at night. | Drug | Nicotine Patch + Denic Smoking, Nicotine Patch + No Smoking |
| Placebo PatchSubjects will wear a placebo patch for 2 fMRIs, each condition lasting 2 days. They will take the patch off at night. | Drug | Placebo Patch + Denic Smoking, Placebo Patch + No Smoking |
Primary outcome
Measure cue reactivity while subjects undergo a functional magnetic resonance imaging (fMRI).
Time frame: 1.25 hours
1 secondary outcome
Measure continuous working memory while subjects are scanned in a functional magnetic resonance imaging (fMRI).
Time frame: 1.25 hours
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Jan 2017.
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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.
Joseph McClernon, Ph.D principal investigator
Duke University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Quit smoking and Nicotine patch in people with Smoking, run by Duke University 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 6 inclusion and 9 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 31 Jan 2017. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Measure cue reactivity while subjects undergo a functional magnetic resonance imaging (fMRI). (time frame: 1.25 hours). 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 31 Jan 2017.