<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT01704573</url>
  </required_header>
  <id_info>
    <org_study_id>812051</org_study_id>
    <secondary_id>P50CA143187</secondary_id>
    <nct_id>NCT01704573</nct_id>
  </id_info>
  <brief_title>Nicotinic Receptor Levels After Stopping Smoking</brief_title>
  <official_title>Nicotinic Receptor Availability in Slow and Fast Nicotine Metabolizers</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Pennsylvania</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Pfizer</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Pennsylvania</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This positron emission tomography (PET) study examines the effects of 24 hours abstinence&#xD;
      from smoking on return to availability of neuronal nicotinic receptors in slow and fast&#xD;
      metabolizers of nicotine.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The nicotine metabolite ratio (NMR), a stable marker of nicotine clearance rate, is a robust&#xD;
      predictor of smoking relapse. Individuals who are fast nicotine metabolizers have higher&#xD;
      rates of relapse, compared to slow metabolizers, on nicotine replacement or placebo&#xD;
      treatment. Nicotine exerts its reinforcing properties, in part, by binding to α4β2* nicotinic&#xD;
      acetylcholine receptors (nAChRs) in the brain. The α4β2* nAChRs are abundant and have high&#xD;
      affinity for nicotine relative to other nAChR subtypes. The goal of this project is to&#xD;
      identify abstinence-induced changes in neuronal nicotinic receptor availability that may&#xD;
      underlie risk for smoking relapse.&#xD;
&#xD;
      The investigators propose to utilize positron emission tomography (PET) imaging to examine&#xD;
      the association of variation in nicotine metabolism with return to availability of α4β2*&#xD;
      nAChRs during early abstinence. The investigators will measure α4β2* receptor availability&#xD;
      using the PET radio-ligand 2-[18F]FA, administered with bolus injection, on two separate&#xD;
      occasions: during smoking as usual and after 24 hours of abstinence. The proposed study will&#xD;
      help us understand the neurochemical mechanisms that underlie the higher risk of relapse&#xD;
      among faster nicotine metabolizers, thereby pointing to potential targets for tailored&#xD;
      therapy for these smokers at increased risk.&#xD;
&#xD;
      In addition, the investigators will invite six subjects who have completed the two PET scans&#xD;
      described above to complete a third PET scan. During this third PET scan, the investigators&#xD;
      plan to measure α4β2* receptor availability using the PET radio-ligand 2-[18F]FA,&#xD;
      administered as bolus plus constant infusion after 24 hours of abstinence. The purpose will&#xD;
      be to compare α4β2* nAChR binding potential data from the bolus 2-[18F]FA infusion protocol&#xD;
      used in the main study to the bolus plus constant infusion protocol used in this third PET&#xD;
      scan.&#xD;
&#xD;
      The protocol of this third PET scan will help the investigators demonstrate the feasibility&#xD;
      at the University of Pennsylvania of administering the radiotracer as a bolus plus constant&#xD;
      infusion, and the feasibility of scanning for two hours (versus one hour in the current&#xD;
      protocol) paradigm. This data is important pilot data for future NIH grant submissions using&#xD;
      this radiotracer.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>October 2010</start_date>
  <completion_date type="Actual">December 2012</completion_date>
  <primary_completion_date type="Actual">March 2012</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Change in α4β2* nAChR binding potential</measure>
    <time_frame>Week 1 and up to Week 5</time_frame>
    <description>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.&#xD;
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.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Cigarette craving</measure>
    <time_frame>Week 0, Week 1, and up to Week 5</time_frame>
    <description>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).&#xD;
During each PET scanning session, the measure will be administered both before and after the PET scan.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Behavioral Performance on cognitive tasks</measure>
    <time_frame>Week 1 and up to Week 5</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Actual">20</enrollment>
  <condition>Nicotine Addiction</condition>
  <arm_group>
    <arm_group_label>NMR by abstinence status</arm_group_label>
    <description>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.&#xD;
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.&#xD;
All participants who complete both PET scans will also complete an anatomical MRI scan.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>2-[18F]-fluro-3-[2(S)-2-azethidinylmethoxy]-pyridine</intervention_name>
    <description>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.&#xD;
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.</description>
    <arm_group_label>NMR by abstinence status</arm_group_label>
    <other_name>2-[18F]FA, 2-FA</other_name>
  </intervention>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Two saliva samples will be collected at the medical screening session. A 6ml saliva sample&#xD;
      will be used for nicotine metabolite ratio (NMR) estimation, and a 2ml saliva sample for DNA&#xD;
      extraction (using an Oragene collection kit).&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        20 adult, non-treatment seeking smokers, reporting consumption of greater than/equal to 10&#xD;
        cigarettes per day for at least 6 months will be the target population for the study.&#xD;
        Participants will first be screened over the phone and then complete an in-person medical&#xD;
        screen to ensure final eligibility. Enrolled participants will complete 2 PET scans and an&#xD;
        MRI scan.&#xD;
&#xD;
        6 smokers who have completed the study and have agreed to be re-contacted for future&#xD;
        studies will be invited to participate in an additional procedure. Participants will be&#xD;
        screened over the phone and complete an in-person medical screen to ensure final&#xD;
        eligibility. Enrolled participants will complete 1 PET scan.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Ages 18 to 65 years old.&#xD;
&#xD;
          2. Smoke 10 cigarettes per day for the previous 6 months.&#xD;
&#xD;
          3. Weigh less than 300lbs (due to limitations of the PET and MRI scanners).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Smoking behavior:&#xD;
&#xD;
               1. Current enrollment or plans to enroll in a smoking cessation program, or use&#xD;
                  other smoking cessation medications in the next 2 months.&#xD;
&#xD;
               2. Provide a CO reading of less than 10 ppm at medical screening.&#xD;
&#xD;
          2. Alcohol/Drugs:&#xD;
&#xD;
               1. History of substance abuse and/or currently receiving treatment for substance&#xD;
                  abuse (e.g., alcohol, opioids, cocaine, marijuana, or stimulants).&#xD;
&#xD;
               2. Positive drug screen at any of the sessions (see page 8 for list of drugs and/or&#xD;
                  contra-indicated medications).&#xD;
&#xD;
               3. Current alcohol consumption that exceeds 25 standard drinks/week.&#xD;
&#xD;
               4. Providing a breath alcohol concentration (BrAC) reading of greater than or equal&#xD;
                  to 0.01 at any session.&#xD;
&#xD;
          3. Medical:&#xD;
&#xD;
               1. Women who are pregnant, planning a pregnancy, or lactating; all female subjects&#xD;
                  shall undergo a serum pregnancy test at the medical screening session and urine&#xD;
                  pregnancy tests at the two PET scans and MRI scan.&#xD;
&#xD;
               2. Women of child-bearing age must agree in writing to use an approved method of&#xD;
                  contraception or agree to abstain from sexual intercourse&#xD;
&#xD;
               3. History or current diagnosis of the following psychiatric diagnoses identified by&#xD;
                  the MINI (Mini International Neuropsychiatric Interview) such as psychosis,&#xD;
                  bipolar disorder, schizophrenia, major current depression, or any Axis 1 disorder&#xD;
&#xD;
               4. Self-report of serious or unstable disease within the past 6 months (e.g., cancer&#xD;
                  [except melanoma], HIV/AIDS, stroke, angina, coronary disease, heart attack).&#xD;
&#xD;
               5. History of epilepsy or a seizure disorder.&#xD;
&#xD;
               6. Any medical or neurological condition that might interfere with the distribution&#xD;
                  of the radiotracer as determined by the study M.D.&#xD;
&#xD;
          4. Medication:&#xD;
&#xD;
             a. Current use or recent discontinuation (within last 14-days) of the following&#xD;
             medications:&#xD;
&#xD;
               -  Any form of smoking cessation medication (Zyban, Wellbutrin, Wellbutrin SR,&#xD;
                  Chantix, NRT);&#xD;
&#xD;
               -  Recent (within last 14 days) or planned use of psychotropic medications&#xD;
                  (anti-psychotics, anti-depressants, anti-anxiety, anti-panic medications, mood&#xD;
                  stabilizers, opioids, and stimulants).&#xD;
&#xD;
               -  Participants shall be instructed to refrain from using any study prohibited drugs&#xD;
                  (note - participants are allowed to take prescription medicines not in the&#xD;
                  exclusion list) throughout their participation in the study.&#xD;
&#xD;
          5. Imaging-Related Exclusion Criteria:&#xD;
&#xD;
               1. Self-reported history of head trauma or brain (or CNS) tumor.&#xD;
&#xD;
               2. Self-reported history of claustrophobia (contraindicated for PET and MRI).&#xD;
&#xD;
               3. Having a cochlear implant or wearing bilateral hearing aids.&#xD;
&#xD;
               4. Self-reported use of pacemakers, certain metallic implants, or presence of metal&#xD;
                  in the eye as contraindicated for MRI.&#xD;
&#xD;
               5. History of gunshot wound.&#xD;
&#xD;
               6. Circumstances or conditions that may interfere with magnetic resonance imaging&#xD;
                  (MRI)&#xD;
&#xD;
               7. Inability to complete the baseline study procedures within four hours and/or&#xD;
                  correctly, as determined by the PI.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Caryn Lerman, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Pennsylvania</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Center for Interdisciplinary Research on Nicotine Addiction, University of Pennsylvania</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://www.med.upenn.edu/cirna/</url>
    <description>CIRNA website</description>
  </link>
  <verification_date>June 2017</verification_date>
  <study_first_submitted>October 2, 2012</study_first_submitted>
  <study_first_submitted_qc>October 9, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 11, 2012</study_first_posted>
  <last_update_submitted>June 14, 2017</last_update_submitted>
  <last_update_submitted_qc>June 14, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">June 16, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>PET Scan</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Tobacco Use Disorder</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT01704573
org study id: 812051
secondary id: P50CA143187
nct id: NCT01704573
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
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.
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.
observational model: Cohort
time perspective: Prospective
measure: Change in α4β2* nAChR binding potential
time frame: Week 1 and up to Week 5
description: 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.
measure: Cigarette craving
time frame: Week 0, Week 1, and up to Week 5
description: 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.
measure: Behavioral Performance on cognitive tasks
time frame: Week 1 and up to Week 5
description: 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.
arm group label: NMR by abstinence status
description: 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.
intervention type: Drug
intervention name: 2-[18F]-fluro-3-[2(S)-2-azethidinylmethoxy]-pyridine
description: 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.
arm group label: NMR by abstinence status
other name: 2-[18F]FA, 2-FA
Two saliva samples will be collected at the medical screening session. A 6ml saliva sample
      will be used for nicotine metabolite ratio (NMR) estimation, and a 2ml saliva sample for DNA
      extraction (using an Oragene collection kit).
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Caryn Lerman, PhD
role: Principal Investigator
affiliation: University of Pennsylvania
facility: 
country: United States
url: http://www.med.upenn.edu/cirna/
description: CIRNA website
responsible party type: Sponsor
mesh term: Tobacco Use Disorder
sharing ipd: No