Nicotine AddictionNCT01704573
Nicotinic Receptor Levels After Stopping Smoking
An observational study of Nicotine Addiction, run by University of Pennsylvania at 1 site in United States.
Trial summary
This positron emission tomography (PET) study examines the effects of 24 hours abstinence from smoking on return to availability of neuronal nicotinic receptors in slow and fast metabolizers of nicotine. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Nicotine Addiction
- What is being tested?
- 2-[18F]-fluro-3-[2(S)-2-azethidinylmethoxy]-pyridine
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2010to Dec 2012
- Phase
- Observational
- 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 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: 20 adult, non-treatment seeking smokers, reporting consumption of greater than/equal to 10 cigarettes per day for at least 6 months will be the target population for the study. Participants will first be screened over the phone and then complete an in-person medical screen to ensure final eligibility. Enrolled participants will complete 2 PET scans and an MRI scan. 6 smokers who have completed the study and have agreed to be re-contacted for future studies will be invited to participate in an additional procedure. Participants will be screened over the phone and complete an in-person medical screen to ensure final eligibility. Enrolled participants will complete 1 PET scan.
Who may be able to join
- Ages 18 to 65 years old.
- Smoke 10 cigarettes per day for the previous 6 months.
- Weigh less than 300lbs (due to limitations of the PET and MRI scanners).
Who cannot join
- Smoking behavior:
- Current enrollment or plans to enroll in a smoking cessation program, or use other smoking cessation medications in the next 2 months.
- Provide a CO reading of less than 10 ppm at medical screening.
- Alcohol/Drugs:
- History of substance abuse and/or currently receiving treatment for substance abuse (e.g., alcohol, opioids, cocaine, marijuana, or stimulants).
- Positive drug screen at any of the sessions (see page 8 for list of drugs and/or contra-indicated medications).
Show all 28Show fewer
- Current alcohol consumption that exceeds 25 standard drinks/week.
- Providing a breath alcohol concentration (BrAC) reading of greater than or equal to 0.01 at any session.
- Medical:
- Women who are pregnant, planning a pregnancy, or lactating; all female subjects shall undergo a serum pregnancy test at the medical screening session and urine pregnancy tests at the two PET scans and MRI scan.
- Women of child-bearing age must agree in writing to use an approved method of contraception or agree to abstain from sexual intercourse
- History or current diagnosis of the following psychiatric diagnoses identified by the MINI (Mini International Neuropsychiatric Interview) such as psychosis, bipolar disorder, schizophrenia, major current depression, or any Axis 1 disorder
- Self-report of serious or unstable disease within the past 6 months (e.g., cancer [except melanoma], HIV/AIDS, stroke, angina, coronary disease, heart attack).
- History of epilepsy or a seizure disorder.
- Any medical or neurological condition that might interfere with the distribution of the radiotracer as determined by the study M.D.
- Medication:
- Current use or recent discontinuation (within last 14-days) of the following medications:
- Any form of smoking cessation medication (Zyban, Wellbutrin, Wellbutrin SR, Chantix, NRT);
- Recent (within last 14 days) or planned use of psychotropic medications (anti-psychotics, anti-depressants, anti-anxiety, anti-panic medications, mood stabilizers, opioids, and stimulants).
- Participants shall be instructed to refrain from using any study prohibited drugs (note - participants are allowed to take prescription medicines not in the exclusion list) throughout their participation in the study.
- Imaging-Related Exclusion Criteria:
- Self-reported history of head trauma or brain (or CNS) tumor.
- Self-reported history of claustrophobia (contraindicated for PET and MRI).
- Having a cochlear implant or wearing bilateral hearing aids.
- Self-reported use of pacemakers, certain metallic implants, or presence of metal in the eye as contraindicated for MRI.
- History of gunshot wound.
- Circumstances or conditions that may interfere with magnetic resonance imaging (MRI)
- Inability to complete the baseline study procedures within four hours and/or correctly, as determined by the PI.
Trial locations and contacts
1 site in 1 country.
United States1 site
Center for Interdisciplinary Research on Nicotine Addiction, University of Pennsylvania
Philadelphia, Pennsylvania, 19104
About this study
Official title: Nicotinic Receptor Availability in Slow and Fast Nicotine Metabolizers
This positron emission tomography (PET) study examines the effects of 24 hours abstinence from smoking on return to availability of neuronal nicotinic receptors in slow and fast metabolizers of nicotine.
Read the detailed description
The nicotine metabolite ratio (NMR), a stable marker of nicotine clearance rate, is a robust predictor of smoking relapse. Individuals who are fast nicotine metabolizers have higher rates of relapse, compared to slow metabolizers, on nicotine replacement or placebo treatment. Nicotine exerts its reinforcing properties, in part, by binding to α4β2* nicotinic acetylcholine receptors (nAChRs) in the brain. The α4β2* nAChRs are abundant and have high affinity for nicotine relative to other nAChR subtypes. The goal of this project is to identify abstinence-induced changes in neuronal nicotinic receptor availability that may underlie risk for smoking relapse.
The investigators propose to utilize positron emission tomography (PET) imaging to examine the association of variation in nicotine metabolism with return to availability of α4β2* nAChRs during early abstinence. The investigators will measure α4β2* receptor availability using the PET radio-ligand 2-[18F]FA, administered with bolus injection, on two separate occasions: during smoking as usual and after 24 hours of abstinence. The proposed study will help us understand the neurochemical mechanisms that underlie the higher risk of relapse among faster nicotine metabolizers, thereby pointing to potential targets for tailored therapy for these smokers at increased risk.
In addition, the investigators will invite six subjects who have completed the two PET scans described above to complete a third PET scan. During this third PET scan, the investigators plan to measure α4β2* receptor availability using the PET radio-ligand 2-[18F]FA, administered as bolus plus constant infusion after 24 hours of abstinence. The purpose will be to compare α4β2* nAChR binding potential data from the bolus 2-[18F]FA infusion protocol used in the main study to the bolus plus constant infusion protocol used in this third PET scan.
The protocol of this third PET scan will help the investigators demonstrate the feasibility at the University of Pennsylvania of administering the radiotracer as a bolus plus constant infusion, and the feasibility of scanning for two hours (versus one hour in the current protocol) paradigm. This data is important pilot data for future NIH grant submissions using this radiotracer.
- Conditions
- Nicotine Addiction
- Being tested
- 2-[18F]-fluro-3-[2(S)-2-azethidinylmethoxy]-pyridine
- Keywords
- PET Scan
- 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.
2-[18F]-fluro-3-[2(S)-2-azethidinylmethoxy]-pyridineDrug
Also called 2-[18F]FA, 2-FA
The study will be performed using an Investigational New Drug (IND) Application for the 2-[18F]FA radioligand. The 2-[18F]FA radiotracer allows us to measure nicotine receptors. The PET imaging technique used at these sessions allows us to measure the amount of light that 2-[18F]FA gives off in different regions of the brain, we can estimate how many nicotine receptors are in that region.
2-[18F]FA (radiotracer) is investigational, which means it is not approved by the United States Food and Drug Administration (FDA) for the way that it is being used in this research study. For this reason, we have received approval for all procedures in the current study including the use of 2-[18F]FA from the FDA.
| Study group | Role | What they receive |
|---|---|---|
| NMR by abstinence status | This study uses a mixed design with one between-subject factor (NMR: continuous variable) and one within-subject factor (session: 24 hours abstinent vs. smoking as usual) to examine NMR by abstinence status interactions on α4β2* nAChR availability using 2-[18F]-fluro-3-[2(S)-2-azethidinylmethoxy]-pyridine (2-[18F]FA) PET imaging.
Subjects will participate in two one-hour PET sessions: a) after smoking as usual (smoking exposure standardized) and b) the other following 24 hours of smoking abstinence.
All participants who complete both PET scans will also complete an anatomical MRI scan. Receives: Drug: 2-[18F]-fluro-3-[2(S)-2-azethidinylmethoxy]-pyridine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in α4β2* nAChR binding potential
This study uses a mixed design. A within-subject positron emission tomography (PET) study comparing α4β2* nAChR availability, using 2-[18F]FA PET imaging, at two timepoints (1) during smoking as usual; and (2) after 24 hours of overnight abstinence. The order of the PET scans will be counterbalanced across subjects to prevent order effects that could bias the study results. Nicotine metabolite ratio (NMR) serves as the between-subject factor.
The minimum amount of time between scans will be separated by one week. The maximum amount of time allowable between scans will be 4 weeks.
Measured: Week 1 and up to Week 5
Secondary outcomes (2)
Cigarette craving
The 10-item brief QSU (QSU-B) questionnaire will be used to assess smoking urges at medical screening and at each PET scanning session. The QSU contains 2 subscales (anticipation of reward, relief from negative affect).
During each PET scanning session, the measure will be administered both before and after the PET scan.
Measured: Week 0, Week 1, and up to Week 5
Behavioral Performance on cognitive tasks
Explore potential correlations between α4β2* nAChR availability (smoking versus abstinence) with cognitive performance using 3 computer tasks: an N-back task assessing working memory, a continuous performance task assessing sustained attention, and a task assessing attentional bias to smoking cues.
Measured: Week 1 and up to Week 5
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Oct 2012 (estimated)
- Study startOct 2010
- Primary completionMar 2012
- Study completionDec 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Nicotine AddictionStudies of the same condition, open and under way.
- More trials run by University of PennsylvaniaThe 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Pennsylvania
- Sponsor type
- University, hospital or other
- Collaborators
- Pfizer, National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Caryn Lerman, PhD, Principal investigator, University of Pennsylvania
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01704573
- Sponsor's protocol ID
- 812051
- Other IDs
- P50CA143187
- Status last verified
- Jun 2017
- First submitted
- 2 Oct 2012
- Last updated
- 16 Jun 2017
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Jun 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Nicotinic Receptor Availability in Slow and Fast Nicotine Metabolizers
- ClinicalTrials.gov ID
- NCT01704573
- Acronym / sponsor ID
- 812051
- Conditions
- Nicotine Addiction
- Keywords
- PET Scan
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- University of PennsylvaniaUniversity, hospital or other
- Collaborators
- Pfizer, National Cancer Institute (NCI)
- Study start
- Oct 2010
- Primary completion
- Mar 2012 (actual)
- Study completion
- Dec 2012 (actual)
- First posted
- 11 Oct 2012 (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.
This positron emission tomography (PET) study examines the effects of 24 hours abstinence from smoking on return to availability of neuronal nicotinic receptors in slow and fast metabolizers of nicotine.
Detailed description
The nicotine metabolite ratio (NMR), a stable marker of nicotine clearance rate, is a robust predictor of smoking relapse. Individuals who are fast nicotine metabolizers have higher rates of relapse, compared to slow metabolizers, on nicotine replacement or placebo treatment. Nicotine exerts its reinforcing properties, in part, by binding to α4β2* nicotinic acetylcholine receptors (nAChRs) in the brain. The α4β2* nAChRs are abundant and have high affinity for nicotine relative to other nAChR subtypes. The goal of this project is to identify abstinence-induced changes in neuronal nicotinic receptor availability that may underlie risk for smoking relapse.
The investigators propose to utilize positron emission tomography (PET) imaging to examine the association of variation in nicotine metabolism with return to availability of α4β2* nAChRs during early abstinence. The investigators will measure α4β2* receptor availability using the PET radio-ligand 2-[18F]FA, administered with bolus injection, on two separate occasions: during smoking as usual and after 24 hours of abstinence. The proposed study will help us understand the neurochemical mechanisms that underlie the higher risk of relapse among faster nicotine metabolizers, thereby pointing to potential targets for tailored therapy for these smokers at increased risk.
In addition, the investigators will invite six subjects who have completed the two PET scans described above to complete a third PET scan. During this third PET scan, the investigators plan to measure α4β2* receptor availability using the PET radio-ligand 2-[18F]FA, administered as bolus plus constant infusion after 24 hours of abstinence. The purpose will be to compare α4β2* nAChR binding potential data from the bolus 2-[18F]FA infusion protocol used in the main study to the bolus plus constant infusion protocol used in this third PET scan.
The protocol of this third PET scan will help the investigators demonstrate the feasibility at the University of Pennsylvania of administering the radiotracer as a bolus plus constant infusion, and the feasibility of scanning for two hours (versus one hour in the current protocol) paradigm. This data is important pilot data for future NIH grant submissions using this radiotracer.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| NMR by abstinence status | – | Drug: 2-[18F]-fluro-3-[2(S)-2-azethidinylmethoxy]-pyridineThis study uses a mixed design with one between-subject factor (NMR: continuous variable) and one within-subject factor (session: 24 hours abstinent vs. smoking as usual) to examine NMR by abstinence status interactions on α4β2* nAChR availability using 2-[18F]-fluro-3-[2(S)-2-azethidinylmethoxy]-pyridine (2-[18F]FA) PET imaging. Subjects will participate in two one-hour PET sessions: a) after smoking as usual (smoking exposure standardized) and b) the other following 24 hours of smoking abstinence. All participants who complete both PET scans will also complete an anatomical MRI scan. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- 20 adult, non-treatment seeking smokers, reporting consumption of greater than/equal to 10 cigarettes per day for at least 6 months will be the target population for the study. Participants will first be screened over the phone and then complete an in-person medical screen to ensure final eligibility. Enrolled participants will complete 2 PET scans and an MRI scan. 6 smokers who have completed the study and have agreed to be re-contacted for future studies will be invited to participate in an additional procedure. Participants will be screened over the phone and complete an in-person medical screen to ensure final eligibility. Enrolled participants will complete 1 PET scan.
Key inclusion criteria (3 listed)
- Ages 18 to 65 years old.
- Smoke 10 cigarettes per day for the previous 6 months.
- Weigh less than 300lbs (due to limitations of the PET and MRI scanners).
Key exclusion criteria (28 listed)
- Smoking behavior:
- Alcohol/Drugs:
- Medical:
- Medication:
- Imaging-Related Exclusion Criteria:
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 |
|---|---|---|
| 2-[18F]-fluro-3-[2(S)-2-azethidinylmethoxy]-pyridineAlso: 2-[18F]FA, 2-FAThe study will be performed using an Investigational New Drug (IND) Application for the 2-[18F]FA radioligand. The 2-[18F]FA radiotracer allows us to measure nicotine receptors. The PET imaging technique used at these sessions allows us to measure the amount of light that 2-[18F]FA gives off in different regions of the brain, we can estimate how many nicotine receptors are in that region. 2-[18F]FA (radiotracer) is investigational, which means it is not approved by the United States Food and Drug Administration (FDA) for the way that it is being used in this research study. For this reason, we have received approval for all procedures in the current study including the use of 2-[18F]FA from the FDA. | Drug | NMR by abstinence status |
Primary outcome
Change in α4β2* nAChR binding potential
Time frame: Week 1 and up to Week 5
This study uses a mixed design. A within-subject positron emission tomography (PET) study comparing α4β2* nAChR availability, using 2-[18F]FA PET imaging, at two timepoints (1) during smoking as usual; and (2) after 24 hours of overnight abstinence. The order of the PET scans will be counterbalanced across subjects to prevent order effects that could bias the study results. Nicotine metabolite ratio (NMR) serves as the between-subject factor. The minimum amount of time between scans will be separated by one week. The maximum amount of time allowable between scans will be 4 weeks.
2 secondary outcomes
Cigarette craving
Time frame: Week 0, Week 1, and up to Week 5
Behavioral Performance on cognitive tasks
Time frame: Week 1 and up to Week 5
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 16 Jun 2017.
- CIRNA websiteLink provided by the sponsor.
- Individual participant dataSharing planned: No
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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.
Caryn Lerman, PhD principal investigator
University of Pennsylvania
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Nicotine Addiction, run by University of Pennsylvania 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 3 inclusion and 28 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 16 Jun 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.
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?
Change in α4β2* nAChR binding potential (time frame: Week 1 and up to Week 5). 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 16 Jun 2017.