<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/NCT01721473</url>
  </required_header>
  <id_info>
    <org_study_id>NURA-02-11S</org_study_id>
    <nct_id>NCT01721473</nct_id>
  </id_info>
  <brief_title>Brain Nicotine Receptor Density in Veteran Smokers</brief_title>
  <acronym>BNRDVS</acronym>
  <official_title>Nicotinic Acetylcholine Receptor Density and Veteran Cigarette Smokers</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>VA Office of Research and Development</agency>
      <agency_class>U.S. Fed</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>VA Office of Research and Development</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Cigarette smoking is more prevalent among Veterans (27%) than the general U.S. population&#xD;
      (21%). Smoking is common among people who use marijuana or caffeine heavily, and the use of&#xD;
      menthol cigarettes is becoming increasingly common, affecting approximately 9% of the Veteran&#xD;
      population. Recent research by the group and others indicates that heavy marijuana or&#xD;
      caffeine use, or the use of predominantly menthol cigarettes, can alter brain nicotinic&#xD;
      acetylcholine receptor (nAChR) densities. For the proposed study, brain imaging with PET&#xD;
      scanning will be used to determine nicotine receptor densities in Veteran cigarette smokers&#xD;
      with and without heavy marijuana or caffeine use, and in menthol and non-menthol Veteran&#xD;
      smokers. Results of the proposed research may have implications for improving treatments for&#xD;
      Veterans who smoke cigarettes and who have specific drug use co-morbidities or who use&#xD;
      menthol cigarettes.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Despite improvements in tobacco control, the prevalence of Tobacco Dependence (TD) remains&#xD;
      high at 27% among Veterans and 21% among the general U.S. population (~46 million U.S.&#xD;
      adults). Both co-morbid substance use and menthol cigarette preference are important issues&#xD;
      contributing to greater severity of TD. Among smokers, a lifetime history of substance&#xD;
      use/dependence is common and approximately 33% of all smokers use primarily menthol&#xD;
      cigarettes, meaning that roughly 9% of Veterans smoke menthol. In addition to menthol&#xD;
      cigarette usage being prevalent among Veterans, this problem is likely to worsen over time,&#xD;
      because recent military deployments increase the chances of smoking initiation and marketing&#xD;
      of menthol cigarettes is aimed at roughly the age group that comprises the active military.&#xD;
&#xD;
      For substance use/dependence, marijuana (MJ) users are five times more likely than non-MJ&#xD;
      users to smoke tobacco cigarettes, and regular caffeine users are twice as likely as&#xD;
      non-caffeine users to smoke cigarettes. Cigarette smoking contributes greatly to morbidity&#xD;
      and mortality among patients with drug (and alcohol) dependencies, making it vital to&#xD;
      understand better the complex relationship between drug/alcohol dependence and brain nicotine&#xD;
      receptor densities in cigarette smokers.&#xD;
&#xD;
      Based on prior literature and pilot data collected during the previous Merit Review period,&#xD;
      the primary hypotheses for the proposed research are that: 1) Participants who are heavy MJ&#xD;
      users will have higher 4 2* nAChR densities in the thalami (and other brain regions) than&#xD;
      participants who are not heavy MJ users, 2) Participants who are daily heavy caffeine users&#xD;
      will have lower 4 2* nAChR densities in the thalami (and other regions) than participants who&#xD;
      are not heavy daily caffeine users, 3) Densities of 4 2* nAChRs in the thalami (and other&#xD;
      brain regions of interest) will be higher in menthol than non-menthol cigarette smokers, and&#xD;
      4) lesser severity of 4 2* nAChR up-regulation at baseline (along with clinical factors such&#xD;
      as lesser severity of nicotine dependence) will be associated with better treatment outcomes&#xD;
      in a standard smoking cessation program, including an improved likelihood of quitting and/or&#xD;
      decreasing smoking.&#xD;
&#xD;
      To test these hypotheses, cigarette smokers will be recruited through flyers posted at the VA&#xD;
      Greater Los Angeles Healthcare System in areas where smokers are likely to be present.&#xD;
      Participants will undergo the following sequence of procedures: (1) telephone/in-person&#xD;
      screening, (2) a bolus-plus-continuous-infusion 2-FA positron emission tomography (PET)&#xD;
      scanning session, (3) a structural magnetic resonance imaging scan within one week of the&#xD;
      initial PET session, and (4) referral to a standard 12-week smoking cessation program. Rating&#xD;
      scales for the determination of smoking-related symptoms will be collected before and during&#xD;
      the PET scanning procedure. Smoking status and measures of nicotine exposure and metabolism&#xD;
      will be collected during the study using participant reports, exhaled carbon monoxide (CO)&#xD;
      levels, urine cotinine levels, and plasma nicotine, cotinine, and 3'-hydroxycotinine levels.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 1, 2012</start_date>
  <completion_date type="Actual">June 30, 2016</completion_date>
  <primary_completion_date type="Actual">June 30, 2016</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>PET Scan, Rating Scales</measure>
    <time_frame>Primary outcome measures will be determined over approximately 3 weeks</time_frame>
    <description>Vt/fp values (indicating relative densities of alpha4beta2 nicotinic acetylcholine receptors in different brain regions) in various brain regions - can also be referred to as mL/cm3.</description>
  </primary_outcome>
  <number_of_groups>6</number_of_groups>
  <enrollment type="Actual">184</enrollment>
  <condition>Positron Emission Tomography</condition>
  <arm_group>
    <arm_group_label>cigarette smokers with heavy marijuana use</arm_group_label>
    <description>With heavy marijuana use</description>
  </arm_group>
  <arm_group>
    <arm_group_label>cigarette smokers with heavy caffeine use</arm_group_label>
    <description>with heavy caffeine use</description>
  </arm_group>
  <arm_group>
    <arm_group_label>cigarette smokers w/o heavy caffeine and marijuana use</arm_group_label>
    <description>cigarette smokers without the heavy use of marijuana or caffeine</description>
  </arm_group>
  <arm_group>
    <arm_group_label>non-smokers</arm_group_label>
    <description>not a regular cigarette user</description>
  </arm_group>
  <arm_group>
    <arm_group_label>cigarette smokers with non-menthol cigarette preference</arm_group_label>
    <description>non-menthol cigarette preference</description>
  </arm_group>
  <arm_group>
    <arm_group_label>cigarette smokers with menthol cigarette preference</arm_group_label>
    <description>menthol cigarette preference</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>positron emission tomography scan</intervention_name>
    <description>2-FA positron emission tomography scan</description>
    <arm_group_label>cigarette smokers w/o heavy caffeine and marijuana use</arm_group_label>
    <arm_group_label>cigarette smokers with heavy caffeine use</arm_group_label>
    <arm_group_label>cigarette smokers with heavy marijuana use</arm_group_label>
    <arm_group_label>cigarette smokers with menthol cigarette preference</arm_group_label>
    <arm_group_label>cigarette smokers with non-menthol cigarette preference</arm_group_label>
    <arm_group_label>non-smokers</arm_group_label>
  </intervention>
  <biospec_retention>None Retained</biospec_retention>
  <biospec_descr>
    <textblock>
      None retained.&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Veterans who are cigarette smokers (10 to 40 cigarettes per day) who either use significant&#xD;
        amounts of caffeine or marijuana (or who have little or no such use).&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Must be a Veteran cigarette smoker, living within commuting distance of the VA San&#xD;
             Diego Healthcare System&#xD;
&#xD;
          -  Healthy adult Veterans (18 to 65 years old) who are tobacco dependent cigarette&#xD;
             smokers (10 to 40 cigarettes per day) meeting criteria for Nicotine Dependence as&#xD;
             defined by DSM-IV criteria109 and who want to quit smoking.&#xD;
&#xD;
          -  Heavy marijuana or caffeine use (defined as using the equivalent of &gt; 2 marijuana&#xD;
             cigarettes per week or the use of at least 3 coffee cup equivalents per day) for at&#xD;
             least the past 6 months or no heavy drug/alcohol use.&#xD;
&#xD;
          -  Ability to read, write, and give voluntary informed consent.&#xD;
&#xD;
          -  An exhaled CO &gt; 8 ppm during the study screening visit to verify smoking status.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Any Axis I diagnosis (including mood, anxiety, and psychotic disorders) other than&#xD;
             Nicotine, Marijuana, or Caffeine Dependence within the past 1 year.&#xD;
&#xD;
          -  A current diagnosis (within the past month) of other substance abuse/dependence&#xD;
             diagnoses (such as cocaine, amphetamine, or opiates). (Length of abstinence will be&#xD;
             verified through participant interview and a chart review at the initial study visit,&#xD;
             which typically includes information about substance abuse treatment history and&#xD;
             objective verification with breathalyzer and/or urine toxicology screens). Occasional&#xD;
             drug/alcohol use not meeting criteria for abuse/dependence will not be exclusionary.&#xD;
&#xD;
          -  Any current medication or any history of a medical condition that might affect the&#xD;
             central nervous system at the time of scanning (e.g., current treatment with a&#xD;
             psychotropic medication, or history of severe head trauma with loss of consciousness,&#xD;
             epilepsy, or other neurological diseases).&#xD;
&#xD;
          -  The combination of both heavy marijuana and caffeine use.&#xD;
&#xD;
          -  Unstable cardiovascular disease, severe liver disease, or renal insufficiency, which&#xD;
             might make tolerating study procedures difficult. Routine history and physical&#xD;
             examination will be performed at the initial screening visit to insure that&#xD;
             participants meet study criteria (Section D4).&#xD;
&#xD;
          -  Pregnancy (urine pregnancy tests will be obtained on all women of childbearing&#xD;
             potential) due to the theoretical risk of radiation exposure to the fetus.&#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>Arthur L Brody, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>VA San Diego Healthcare System, San Diego, CA</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>VA San Diego Healthcare System, San Diego, CA</name>
      <address>
        <city>San Diego</city>
        <state>California</state>
        <zip>92161</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>VA Greater Los Angeles Healthcare System, West Los Angeles, CA</name>
      <address>
        <city>West Los Angeles</city>
        <state>California</state>
        <zip>90073</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Potenza MN, Brody AL. Commentary on Boileau et al. (2013): Distinguishing D2/D3 dopaminergic contributions to addictions. Addiction. 2013 May;108(5):964-5. doi: 10.1111/add.12119. No abstract available.</citation>
    <PMID>23587083</PMID>
  </reference>
  <reference>
    <citation>Jasinska AJ, Zorick T, Brody AL, Stein EA. Dual role of nicotine in addiction and cognition: a review of neuroimaging studies in humans. Neuropharmacology. 2014 Sep;84:111-22. doi: 10.1016/j.neuropharm.2013.02.015. Epub 2013 Mar 6.</citation>
    <PMID>23474015</PMID>
  </reference>
  <reference>
    <citation>Brody AL, Mukhin AG, Stephanie Shulenberger, Mamoun MS, Kozman M, Phuong J, Neary M, Luu T, Mandelkern MA. Treatment for tobacco dependence: effect on brain nicotinic acetylcholine receptor density. Neuropsychopharmacology. 2013 Jul;38(8):1548-56. doi: 10.1038/npp.2013.53. Epub 2013 Feb 21.</citation>
    <PMID>23429692</PMID>
  </reference>
  <reference>
    <citation>Jarcho JM, Feier NA, Bert A, Labus JA, Lee M, Stains J, Ebrat B, Groman SM, Tillisch K, Brody AL, London ED, Mandelkern MA, Mayer EA. Diminished neurokinin-1 receptor availability in patients with two forms of chronic visceral pain. Pain. 2013 Jul;154(7):987-96. doi: 10.1016/j.pain.2013.02.026. Epub 2013 Mar 5.</citation>
    <PMID>23582152</PMID>
  </reference>
  <reference>
    <citation>Storage S, Mandelkern MA, Phuong J, Kozman M, Neary MK, Brody AL. A positive relationship between harm avoidance and brain nicotinic acetylcholine receptor availability. Psychiatry Res. 2013 Dec 30;214(3):415-21. doi: 10.1016/j.pscychresns.2013.07.010. Epub 2013 Oct 19.</citation>
    <PMID>24148908</PMID>
  </reference>
  <reference>
    <citation>Xu J, Fregni F, Brody AL, Rahman AS. Transcranial direct current stimulation reduces negative affect but not cigarette craving in overnight abstinent smokers. Front Psychiatry. 2013 Sep 20;4:112. doi: 10.3389/fpsyt.2013.00112. eCollection 2013.</citation>
    <PMID>24065930</PMID>
  </reference>
  <reference>
    <citation>Le Foll B, Guranda M, Wilson AA, Houle S, Rusjan PM, Wing VC, Zawertailo L, Busto U, Selby P, Brody AL, George TP, Boileau I. Elevation of dopamine induced by cigarette smoking: novel insights from a [11C]-+-PHNO PET study in humans. Neuropsychopharmacology. 2014 Jan;39(2):415-24. doi: 10.1038/npp.2013.209. Epub 2013 Aug 19.</citation>
    <PMID>23954846</PMID>
  </reference>
  <reference>
    <citation>Zanchi D, Brody AL, Montandon ML, Kopel R, Emmert K, Preti MG, Van De Ville D, Haller S. Cigarette smoking leads to persistent and dose-dependent alterations of brain activity and connectivity in anterior insula and anterior cingulate. Addict Biol. 2015 Nov;20(6):1033-41. doi: 10.1111/adb.12292. Epub 2015 Aug 25.</citation>
    <PMID>26303184</PMID>
  </reference>
  <reference>
    <citation>Brody AL, Zorick T, Hubert R, Hellemann GS, Balali S, Kawasaki SS, Garcia LY, Enoki R, Abraham P, Young P, McCreary C. Combination Extended Smoking Cessation Treatment Plus Home Visits for Smokers With Schizophrenia: A Randomized Controlled Trial. Nicotine Tob Res. 2017 Jan;19(1):68-76. doi: 10.1093/ntr/ntw190. Epub 2016 Aug 3.</citation>
    <PMID>27613888</PMID>
  </reference>
  <reference>
    <citation>Xie J, Douglas PK, Wu YN, Brody AL, Anderson AE. Decoding the encoding of functional brain networks: An fMRI classification comparison of non-negative matrix factorization (NMF), independent component analysis (ICA), and sparse coding algorithms. J Neurosci Methods. 2017 Apr 15;282:81-94. doi: 10.1016/j.jneumeth.2017.03.008. Epub 2017 Mar 18.</citation>
    <PMID>28322859</PMID>
  </reference>
  <results_reference>
    <citation>Brody AL, Mukhin AG, La Charite J, Ta K, Farahi J, Sugar CA, Mamoun MS, Vellios E, Archie M, Kozman M, Phuong J, Arlorio F, Mandelkern MA. Up-regulation of nicotinic acetylcholine receptors in menthol cigarette smokers. Int J Neuropsychopharmacol. 2013 Jun;16(5):957-66. doi: 10.1017/S1461145712001022. Epub 2012 Nov 21.</citation>
    <PMID>23171716</PMID>
  </results_reference>
  <results_reference>
    <citation>Brody AL, Mukhin AG, Mamoun MS, Luu T, Neary M, Liang L, Shieh J, Sugar CA, Rose JE, Mandelkern MA. Brain nicotinic acetylcholine receptor availability and response to smoking cessation treatment: a randomized trial. JAMA Psychiatry. 2014 Jul 1;71(7):797-805. doi: 10.1001/jamapsychiatry.2014.138.</citation>
    <PMID>24850280</PMID>
  </results_reference>
  <results_reference>
    <citation>Zorick T, Mandelkern MA, Brody AL. A naturalistic study of the association between antidepressant treatment and outcome of smoking cessation treatment. J Clin Psychiatry. 2014 Dec;75(12):e1433-8. doi: 10.4088/JCP.14m09012.</citation>
    <PMID>25551240</PMID>
  </results_reference>
  <results_reference>
    <citation>Brody AL, McClernon FJ. Prediction of smoking cessation with treatment: the emerging contribution of brain imaging research. Neuropsychopharmacology. 2015 May;40(6):1309-10. doi: 10.1038/npp.2015.31. No abstract available.</citation>
    <PMID>25868069</PMID>
  </results_reference>
  <results_reference>
    <citation>Dubroff JG, Doot RK, Falcone M, Schnoll RA, Ray R, Tyndale RF, Brody AL, Hou C, Schmitz A, Lerman C. Decreased Nicotinic Receptor Availability in Smokers with Slow Rates of Nicotine Metabolism. J Nucl Med. 2015 Nov;56(11):1724-9. doi: 10.2967/jnumed.115.155002. Epub 2015 Aug 13.</citation>
    <PMID>26272810</PMID>
  </results_reference>
  <results_reference>
    <citation>Brody AL, Hubert R, Mamoun MS, Enoki R, Garcia LY, Abraham P, Young P, Mandelkern MA. Nicotinic acetylcholine receptor availability in cigarette smokers: effect of heavy caffeine or marijuana use. Psychopharmacology (Berl). 2016 Sep;233(17):3249-57. doi: 10.1007/s00213-016-4367-x. Epub 2016 Jul 1.</citation>
    <PMID>27370018</PMID>
  </results_reference>
  <results_reference>
    <citation>Brody AL, Hubert R, Enoki R, Garcia LY, Mamoun MS, Okita K, London ED, Nurmi EL, Seaman LC, Mandelkern MA. Effect of Cigarette Smoking on a Marker for Neuroinflammation: A [11C]DAA1106 Positron Emission Tomography Study. Neuropsychopharmacology. 2017 Jul;42(8):1630-1639. doi: 10.1038/npp.2017.48. Epub 2017 Mar 6. Erratum In: Neuropsychopharmacology. 2018 Mar;43(4):925.</citation>
    <PMID>28262740</PMID>
  </results_reference>
  <verification_date>October 2019</verification_date>
  <study_first_submitted>October 29, 2012</study_first_submitted>
  <study_first_submitted_qc>November 1, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 4, 2012</study_first_posted>
  <results_first_submitted>July 15, 2019</results_first_submitted>
  <results_first_submitted_qc>October 4, 2019</results_first_submitted_qc>
  <results_first_posted type="Actual">October 7, 2019</results_first_posted>
  <last_update_submitted>October 4, 2019</last_update_submitted>
  <last_update_submitted_qc>October 4, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">October 7, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Tobacco</keyword>
  <keyword>Positron Emission Tomography</keyword>
  <keyword>Marijuana</keyword>
  <keyword>Caffeine</keyword>
  <keyword>Menthol</keyword>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Non-smokers</title>
          <description>People who did not smoke or use heavy caffeine or marijuana</description>
        </group>
        <group group_id="P2">
          <title>Menthol Smokers</title>
          <description>People who smoke menthol cigarettes.</description>
        </group>
        <group group_id="P3">
          <title>Non-menthol Smokers</title>
          <description>People who smoke non-menthol cigarettes</description>
        </group>
        <group group_id="P4">
          <title>Smokers Without Comorbidities</title>
          <description>People who smoke without heavy caffeine or marijuana use.</description>
        </group>
        <group group_id="P5">
          <title>Smokers With Caffeine</title>
          <description>People who smoke and have heavy caffeine use.</description>
        </group>
        <group group_id="P6">
          <title>Smokers With Marijuana</title>
          <description>People who smoke and heavily use marijuana.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="47"/>
                <participants group_id="P2" count="22"/>
                <participants group_id="P3" count="41"/>
                <participants group_id="P4" count="34"/>
                <participants group_id="P5" count="22"/>
                <participants group_id="P6" count="18"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="47"/>
                <participants group_id="P2" count="22"/>
                <participants group_id="P3" count="41"/>
                <participants group_id="P4" count="34"/>
                <participants group_id="P5" count="22"/>
                <participants group_id="P6" count="18"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Non-smokers</title>
          <description>People who did not smoke.</description>
        </group>
        <group group_id="B2">
          <title>Smokers Methol</title>
          <description>People who smoke menthol cigarettes.</description>
        </group>
        <group group_id="B3">
          <title>Smokers Non Menthol</title>
          <description>People who smoke non menthol cigarettes.</description>
        </group>
        <group group_id="B4">
          <title>Smokers Without Comorbidities</title>
          <description>People who smoke but do not have heavy caffeine or marijuana use.</description>
        </group>
        <group group_id="B5">
          <title>Smokers With Caffeine</title>
          <description>People who smoke and have heavy caffeine use.</description>
        </group>
        <group group_id="B6">
          <title>Smokers With Marijuana</title>
          <description>People who smoke who have heavy marijuana use</description>
        </group>
        <group group_id="B7">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="47"/>
            <count group_id="B2" value="22"/>
            <count group_id="B3" value="41"/>
            <count group_id="B4" value="34"/>
            <count group_id="B5" value="22"/>
            <count group_id="B6" value="18"/>
            <count group_id="B7" value="184"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="40.5" spread="13.4"/>
                    <measurement group_id="B2" value="43.1" spread="12.9"/>
                    <measurement group_id="B3" value="36.4" spread="14.2"/>
                    <measurement group_id="B4" value="39.1" spread="13.1"/>
                    <measurement group_id="B5" value="46.0" spread="12.9"/>
                    <measurement group_id="B6" value="42.3" spread="12.6"/>
                    <measurement group_id="B7" value="44" spread="13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="14"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="0"/>
                    <measurement group_id="B7" value="21"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="47"/>
                    <measurement group_id="B2" value="15"/>
                    <measurement group_id="B3" value="27"/>
                    <measurement group_id="B4" value="34"/>
                    <measurement group_id="B5" value="22"/>
                    <measurement group_id="B6" value="18"/>
                    <measurement group_id="B7" value="163"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>PET Scan, Rating Scales</title>
        <description>Vt/fp values (indicating relative densities of alpha4beta2 nicotinic acetylcholine receptors in different brain regions) in various brain regions - can also be referred to as mL/cm3.</description>
        <time_frame>Primary outcome measures will be determined over approximately 3 weeks</time_frame>
        <population>Non-smokers and smokers (with the set of different conditions: menthol, non-menthol, w/ caffeine, w/ marijuana, w/o caffeine+marijuana) who underwent PET scanning to measure the total volume of distribution Vt in the prefrontal cortex.</population>
        <group_list>
          <group group_id="O1">
            <title>Smoker vs. Non Smoker</title>
            <description>menthol smoker vs. non-menthol smoker vs. non smoker (w/o caffeine and marijuana) vs. smoker (w/o caffeine and marijuana) vs. smoker w/ caffeine use vs. smoker w/ marijuana use</description>
          </group>
        </group_list>
        <measure>
          <title>PET Scan, Rating Scales</title>
          <description>Vt/fp values (indicating relative densities of alpha4beta2 nicotinic acetylcholine receptors in different brain regions) in various brain regions - can also be referred to as mL/cm3.</description>
          <population>Non-smokers and smokers (with the set of different conditions: menthol, non-menthol, w/ caffeine, w/ marijuana, w/o caffeine+marijuana) who underwent PET scanning to measure the total volume of distribution Vt in the prefrontal cortex.</population>
          <units>Vt/fp or mL/cm3</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="184"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Non-smokers</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="47"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.1" spread="1.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Smokers menthol</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="22"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8.6" spread="1.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Smokers non-menthol</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="41"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.9" spread="1.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Smokers w/o caff+marij</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="34"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8.0" spread="1.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Smokers w/ caff</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="22"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11.9" spread="5.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Smokers w/ marij</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="18"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10.8" spread="2.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>3 weeks</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Non-smokers</title>
          <description>Participants who did not smoke.</description>
        </group>
        <group group_id="E2">
          <title>Smokers Methol</title>
          <description>Participants who smoked menthol cigarettes.</description>
        </group>
        <group group_id="E3">
          <title>Smokers Non Menthol</title>
          <description>Participants who smoked non menthol cigarettes</description>
        </group>
        <group group_id="E4">
          <title>Smokers Without Comorbidities</title>
          <description>Participants who smoked without heavy use of caffeine or marijuana.</description>
        </group>
        <group group_id="E5">
          <title>Smokers With Caffeine</title>
          <description>Participants who smoked with heavy caffeine use.</description>
        </group>
        <group group_id="E6">
          <title>Smokers With Marijuana</title>
          <description>Participants who smoked with heavy marijuana use.</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="47"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="41"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="47"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="41"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="47"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="41"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Arthur Brody</name_or_title>
      <organization>VA San Diego Healthcare System</organization>
      <phone>8585528585</phone>
      <email>arthur.brody@va.gov</email>
    </point_of_contact>
  </clinical_results>
</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/NCT01721473
org study id: NURA-02-11S
nct id: NCT01721473
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
is us export: No
Cigarette smoking is more prevalent among Veterans (27%) than the general U.S. population
      (21%). Smoking is common among people who use marijuana or caffeine heavily, and the use of
      menthol cigarettes is becoming increasingly common, affecting approximately 9% of the Veteran
      population. Recent research by the group and others indicates that heavy marijuana or
      caffeine use, or the use of predominantly menthol cigarettes, can alter brain nicotinic
      acetylcholine receptor (nAChR) densities. For the proposed study, brain imaging with PET
      scanning will be used to determine nicotine receptor densities in Veteran cigarette smokers
      with and without heavy marijuana or caffeine use, and in menthol and non-menthol Veteran
      smokers. Results of the proposed research may have implications for improving treatments for
      Veterans who smoke cigarettes and who have specific drug use co-morbidities or who use
      menthol cigarettes.
Despite improvements in tobacco control, the prevalence of Tobacco Dependence (TD) remains
      high at 27% among Veterans and 21% among the general U.S. population (~46 million U.S.
      adults). Both co-morbid substance use and menthol cigarette preference are important issues
      contributing to greater severity of TD. Among smokers, a lifetime history of substance
      use/dependence is common and approximately 33% of all smokers use primarily menthol
      cigarettes, meaning that roughly 9% of Veterans smoke menthol. In addition to menthol
      cigarette usage being prevalent among Veterans, this problem is likely to worsen over time,
      because recent military deployments increase the chances of smoking initiation and marketing
      of menthol cigarettes is aimed at roughly the age group that comprises the active military.

      For substance use/dependence, marijuana (MJ) users are five times more likely than non-MJ
      users to smoke tobacco cigarettes, and regular caffeine users are twice as likely as
      non-caffeine users to smoke cigarettes. Cigarette smoking contributes greatly to morbidity
      and mortality among patients with drug (and alcohol) dependencies, making it vital to
      understand better the complex relationship between drug/alcohol dependence and brain nicotine
      receptor densities in cigarette smokers.

      Based on prior literature and pilot data collected during the previous Merit Review period,
      the primary hypotheses for the proposed research are that: 1) Participants who are heavy MJ
      users will have higher 4 2* nAChR densities in the thalami (and other brain regions) than
      participants who are not heavy MJ users, 2) Participants who are daily heavy caffeine users
      will have lower 4 2* nAChR densities in the thalami (and other regions) than participants who
      are not heavy daily caffeine users, 3) Densities of 4 2* nAChRs in the thalami (and other
      brain regions of interest) will be higher in menthol than non-menthol cigarette smokers, and
      4) lesser severity of 4 2* nAChR up-regulation at baseline (along with clinical factors such
      as lesser severity of nicotine dependence) will be associated with better treatment outcomes
      in a standard smoking cessation program, including an improved likelihood of quitting and/or
      decreasing smoking.

      To test these hypotheses, cigarette smokers will be recruited through flyers posted at the VA
      Greater Los Angeles Healthcare System in areas where smokers are likely to be present.
      Participants will undergo the following sequence of procedures: (1) telephone/in-person
      screening, (2) a bolus-plus-continuous-infusion 2-FA positron emission tomography (PET)
      scanning session, (3) a structural magnetic resonance imaging scan within one week of the
      initial PET session, and (4) referral to a standard 12-week smoking cessation program. Rating
      scales for the determination of smoking-related symptoms will be collected before and during
      the PET scanning procedure. Smoking status and measures of nicotine exposure and metabolism
      will be collected during the study using participant reports, exhaled carbon monoxide (CO)
      levels, urine cotinine levels, and plasma nicotine, cotinine, and 3'-hydroxycotinine levels.
observational model: Cohort
time perspective: Prospective
measure: PET Scan, Rating Scales
time frame: Primary outcome measures will be determined over approximately 3 weeks
description: Vt/fp values (indicating relative densities of alpha4beta2 nicotinic acetylcholine receptors in different brain regions) in various brain regions - can also be referred to as mL/cm3.
arm group label: cigarette smokers with heavy marijuana use
description: With heavy marijuana use
arm group label: cigarette smokers with heavy caffeine use
description: with heavy caffeine use
arm group label: cigarette smokers w/o heavy caffeine and marijuana use
description: cigarette smokers without the heavy use of marijuana or caffeine
arm group label: non-smokers
description: not a regular cigarette user
arm group label: cigarette smokers with non-menthol cigarette preference
description: non-menthol cigarette preference
arm group label: cigarette smokers with menthol cigarette preference
description: menthol cigarette preference
intervention type: Other
intervention name: positron emission tomography scan
description: 2-FA positron emission tomography scan
arm group label: cigarette smokers w/o heavy caffeine and marijuana use
arm group label: cigarette smokers with heavy caffeine use
arm group label: cigarette smokers with heavy marijuana use
arm group label: cigarette smokers with menthol cigarette preference
arm group label: cigarette smokers with non-menthol cigarette preference
arm group label: non-smokers
None retained.
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Arthur L Brody, MD
role: Principal Investigator
affiliation: VA San Diego Healthcare System, San Diego, CA
facility: 
facility: 
country: United States
citation: Potenza MN, Brody AL. Commentary on Boileau et al. (2013): Distinguishing D2/D3 dopaminergic contributions to addictions. Addiction. 2013 May;108(5):964-5. doi: 10.1111/add.12119. No abstract available.
PMID: 23587083
citation: Jasinska AJ, Zorick T, Brody AL, Stein EA. Dual role of nicotine in addiction and cognition: a review of neuroimaging studies in humans. Neuropharmacology. 2014 Sep;84:111-22. doi: 10.1016/j.neuropharm.2013.02.015. Epub 2013 Mar 6.
PMID: 23474015
citation: Brody AL, Mukhin AG, Stephanie Shulenberger, Mamoun MS, Kozman M, Phuong J, Neary M, Luu T, Mandelkern MA. Treatment for tobacco dependence: effect on brain nicotinic acetylcholine receptor density. Neuropsychopharmacology. 2013 Jul;38(8):1548-56. doi: 10.1038/npp.2013.53. Epub 2013 Feb 21.
PMID: 23429692
citation: Jarcho JM, Feier NA, Bert A, Labus JA, Lee M, Stains J, Ebrat B, Groman SM, Tillisch K, Brody AL, London ED, Mandelkern MA, Mayer EA. Diminished neurokinin-1 receptor availability in patients with two forms of chronic visceral pain. Pain. 2013 Jul;154(7):987-96. doi: 10.1016/j.pain.2013.02.026. Epub 2013 Mar 5.
PMID: 23582152
citation: Storage S, Mandelkern MA, Phuong J, Kozman M, Neary MK, Brody AL. A positive relationship between harm avoidance and brain nicotinic acetylcholine receptor availability. Psychiatry Res. 2013 Dec 30;214(3):415-21. doi: 10.1016/j.pscychresns.2013.07.010. Epub 2013 Oct 19.
PMID: 24148908
citation: Xu J, Fregni F, Brody AL, Rahman AS. Transcranial direct current stimulation reduces negative affect but not cigarette craving in overnight abstinent smokers. Front Psychiatry. 2013 Sep 20;4:112. doi: 10.3389/fpsyt.2013.00112. eCollection 2013.
PMID: 24065930
citation: Le Foll B, Guranda M, Wilson AA, Houle S, Rusjan PM, Wing VC, Zawertailo L, Busto U, Selby P, Brody AL, George TP, Boileau I. Elevation of dopamine induced by cigarette smoking: novel insights from a [11C]-+-PHNO PET study in humans. Neuropsychopharmacology. 2014 Jan;39(2):415-24. doi: 10.1038/npp.2013.209. Epub 2013 Aug 19.
PMID: 23954846
citation: Zanchi D, Brody AL, Montandon ML, Kopel R, Emmert K, Preti MG, Van De Ville D, Haller S. Cigarette smoking leads to persistent and dose-dependent alterations of brain activity and connectivity in anterior insula and anterior cingulate. Addict Biol. 2015 Nov;20(6):1033-41. doi: 10.1111/adb.12292. Epub 2015 Aug 25.
PMID: 26303184
citation: Brody AL, Zorick T, Hubert R, Hellemann GS, Balali S, Kawasaki SS, Garcia LY, Enoki R, Abraham P, Young P, McCreary C. Combination Extended Smoking Cessation Treatment Plus Home Visits for Smokers With Schizophrenia: A Randomized Controlled Trial. Nicotine Tob Res. 2017 Jan;19(1):68-76. doi: 10.1093/ntr/ntw190. Epub 2016 Aug 3.
PMID: 27613888
citation: Xie J, Douglas PK, Wu YN, Brody AL, Anderson AE. Decoding the encoding of functional brain networks: An fMRI classification comparison of non-negative matrix factorization (NMF), independent component analysis (ICA), and sparse coding algorithms. J Neurosci Methods. 2017 Apr 15;282:81-94. doi: 10.1016/j.jneumeth.2017.03.008. Epub 2017 Mar 18.
PMID: 28322859
citation: Brody AL, Mukhin AG, La Charite J, Ta K, Farahi J, Sugar CA, Mamoun MS, Vellios E, Archie M, Kozman M, Phuong J, Arlorio F, Mandelkern MA. Up-regulation of nicotinic acetylcholine receptors in menthol cigarette smokers. Int J Neuropsychopharmacol. 2013 Jun;16(5):957-66. doi: 10.1017/S1461145712001022. Epub 2012 Nov 21.
PMID: 23171716
citation: Brody AL, Mukhin AG, Mamoun MS, Luu T, Neary M, Liang L, Shieh J, Sugar CA, Rose JE, Mandelkern MA. Brain nicotinic acetylcholine receptor availability and response to smoking cessation treatment: a randomized trial. JAMA Psychiatry. 2014 Jul 1;71(7):797-805. doi: 10.1001/jamapsychiatry.2014.138.
PMID: 24850280
citation: Zorick T, Mandelkern MA, Brody AL. A naturalistic study of the association between antidepressant treatment and outcome of smoking cessation treatment. J Clin Psychiatry. 2014 Dec;75(12):e1433-8. doi: 10.4088/JCP.14m09012.
PMID: 25551240
citation: Brody AL, McClernon FJ. Prediction of smoking cessation with treatment: the emerging contribution of brain imaging research. Neuropsychopharmacology. 2015 May;40(6):1309-10. doi: 10.1038/npp.2015.31. No abstract available.
PMID: 25868069
citation: Dubroff JG, Doot RK, Falcone M, Schnoll RA, Ray R, Tyndale RF, Brody AL, Hou C, Schmitz A, Lerman C. Decreased Nicotinic Receptor Availability in Smokers with Slow Rates of Nicotine Metabolism. J Nucl Med. 2015 Nov;56(11):1724-9. doi: 10.2967/jnumed.115.155002. Epub 2015 Aug 13.
PMID: 26272810
citation: Brody AL, Hubert R, Mamoun MS, Enoki R, Garcia LY, Abraham P, Young P, Mandelkern MA. Nicotinic acetylcholine receptor availability in cigarette smokers: effect of heavy caffeine or marijuana use. Psychopharmacology (Berl). 2016 Sep;233(17):3249-57. doi: 10.1007/s00213-016-4367-x. Epub 2016 Jul 1.
PMID: 27370018
citation: Brody AL, Hubert R, Enoki R, Garcia LY, Mamoun MS, Okita K, London ED, Nurmi EL, Seaman LC, Mandelkern MA. Effect of Cigarette Smoking on a Marker for Neuroinflammation: A [11C]DAA1106 Positron Emission Tomography Study. Neuropsychopharmacology. 2017 Jul;42(8):1630-1639. doi: 10.1038/npp.2017.48. Epub 2017 Mar 6. Erratum In: Neuropsychopharmacology. 2018 Mar;43(4):925.
PMID: 28262740
responsible party type: Sponsor
sharing ipd: No
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 