xml: <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/NCT05962229</url>
    </required_header>
    <id_info>
      <org_study_id>22-36348</org_study_id>
      <secondary_id>1R01DA057282-01</secondary_id>
      <nct_id>NCT05962229</nct_id>
    </id_info>
    <brief_title>Comparative Pharmacokinetics and Pharmacodynamics of Synthetic Nicotine</brief_title>
    <official_title>Comparative Pharmacokinetics and Pharmacodynamics of Synthetic Nicotine</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>University of California, San Francisco</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>National Institute on Drug Abuse (NIDA)</agency>
        <agency_class>NIH</agency_class>
      </collaborator>
    </sponsors>
    <source>University of California, San Francisco</source>
    <oversight_info>
      <has_dmc>Yes</has_dmc>
      <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        In a crossover study, experienced electronic cigarette users will vape 3 different forms of&#xD;
        nicotine: natural (derived from tobacco), synthetic, or a 50:50 mixture of both natural and&#xD;
        synthetic. The investigators will compare nicotine metabolism, cardiovascular effects,&#xD;
        patterns of self-administration, and participants' feelings of craving/withdrawal and&#xD;
        enjoyment.&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">September 2023</start_date>
    <completion_date type="Anticipated">September 2025</completion_date>
    <primary_completion_date type="Anticipated">September 2025</primary_completion_date>
    <phase>Phase 1</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>Randomized</allocation>
      <intervention_model>Crossover Assignment</intervention_model>
      <intervention_model_description>Within-subject, single-blinded crossover study. Participants will be randomized to the order of the 3 conditions using a Latin Square design.</intervention_model_description>
      <primary_purpose>Basic Science</primary_purpose>
      <masking>Single (Participant)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Mean Nicotine Exposure Over Time</measure>
      <time_frame>Up to 7 hours</time_frame>
      <description>Plasma nicotine area under the concentrated time curve (AUC) (ng/ml*h)</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Mean Amount of Nicotine Consumed Over Time</measure>
      <time_frame>120 minutes</time_frame>
      <description>Nicotine self-administration determined by device weight change before and after use multiplied by the nicotine concentration in the e-liquid</description>
    </secondary_outcome>
    <number_of_arms>3</number_of_arms>
    <enrollment type="Anticipated">18</enrollment>
    <condition>Nicotine Dependence</condition>
    <condition>Nicotine Vaping</condition>
    <arm_group>
      <arm_group_label>S-nicotine (tobacco) as the starting condition</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Participants will spend 8 hours in the hospital research ward where they will vape e-liquid containing 100% (S)-nicotine.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>R-nicotine (synthetic) as the starting condition</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Participants will spend 8 hours in the hospital research ward where they will vape e-liquid containing 100% (R)-nicotine.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Racemic (50:50 S- and R- nicotine) as the starting condition</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Participants will spend 8 hours in the hospital research ward where they will vape e-liquid containing 50% (S)-nicotine and 50% (R)-nicotine.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>(S)-Nicotine</intervention_name>
      <description>Participants will spend 8 hours in the hospital research ward and will vape e-liquid containing 100% (S)-nicotine. They will vape following a standardized session, followed by a 4 hour abstinence period. Participants will then vape as they wish (ad libitum) for 90 minutes.</description>
      <arm_group_label>R-nicotine (synthetic) as the starting condition</arm_group_label>
      <arm_group_label>Racemic (50:50 S- and R- nicotine) as the starting condition</arm_group_label>
      <arm_group_label>S-nicotine (tobacco) as the starting condition</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>(R)- nicotine</intervention_name>
      <description>Participants will spend 8 hours in the hospital research ward and will vape e-liquid containing 100% (R)-nicotine. They will vape following a standardized session, followed by a 4 hour abstinence period. Participants will then vape as they wish (ad libitum) for 90 minutes.</description>
      <arm_group_label>R-nicotine (synthetic) as the starting condition</arm_group_label>
      <arm_group_label>Racemic (50:50 S- and R- nicotine) as the starting condition</arm_group_label>
      <arm_group_label>S-nicotine (tobacco) as the starting condition</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Racemic nicotine</intervention_name>
      <description>Participants will spend 8 hours in the hospital research ward and will vape e-liquid containing 50% (R)-nicotine and 50% (S)-nicotine. They will vape following a standardized session, followed by a 4 hour abstinence period. Participants will then vape as they wish (ad libitum) for 90 minutes.</description>
      <arm_group_label>R-nicotine (synthetic) as the starting condition</arm_group_label>
      <arm_group_label>Racemic (50:50 S- and R- nicotine) as the starting condition</arm_group_label>
      <arm_group_label>S-nicotine (tobacco) as the starting condition</arm_group_label>
      <other_name>50:50 mixture of (S)- and (R)-nicotine</other_name>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Healthy on the basis of medical history and limited physical examination.&#xD;
  &#xD;
            -  Current regular user of E-Cigarettes (≥ 15 days in the past 30 days)&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  • Medications&#xD;
  &#xD;
                 -  Use of medications that are inducers of nicotine metabolizing enzyme CYP2A6&#xD;
                    (Example: rifampicin, carbamazepine, phenobarbital, and other anticonvulsant&#xD;
                    drugs).&#xD;
  &#xD;
                 -  Use of sympatholytic medications for cardiovascular conditions including&#xD;
                    hypertension (Example: beta and alpha-blockers).&#xD;
  &#xD;
                 -  Concurrent use of nicotine-containing medications (Example: nicotine patch,&#xD;
                    lozenge, gum).&#xD;
  &#xD;
                 -  Any stimulant medications (example: Adderall) generally given for ADHD treatment.&#xD;
  &#xD;
                    • Pregnancy&#xD;
  &#xD;
                 -  Pregnancy (self-reported and urine pregnancy test)&#xD;
  &#xD;
                 -  Breastfeeding (determined by self-report)&#xD;
  &#xD;
                 -  Women of childbearing potential must be using an acceptable method of&#xD;
                    contraception&#xD;
  &#xD;
                      -  Inability to read and write in English&#xD;
  &#xD;
                      -  A known propylene glycol/vegetable glycerin allergy&#xD;
  &#xD;
                      -  Uncomfortable with getting blood drawn&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>21 Years</minimum_age>
      <maximum_age>65 Years</maximum_age>
      <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Neal Benowitz, MD</last_name>
      <role>Principal Investigator</role>
      <affiliation>University of California, San Francisco</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Lisa Lawrence</last_name>
      <phone>628-206-4204</phone>
      <email>lisa.lawrence@ucsf.edu</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Armando Barraza</last_name>
      <phone>510-560-4842</phone>
      <email>armando.barraza@ucsf.edu</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>Zuckerberg San Francisco General Hospital (ZSFG)</name>
        <address>
          <city>San Francisco</city>
          <state>California</state>
          <zip>94110</zip>
          <country>United States</country>
        </address>
      </facility>
      <contact>
        <last_name>Lisa Lawrence</last_name>
        <phone>628-206-4204</phone>
        <email>lisa.lawrence@ucsf.edu</email>
      </contact>
      <contact_backup>
        <last_name>Armando Barraza</last_name>
        <phone>510-560-4842</phone>
        <email>armando.barraza@ucsf.edu</email>
      </contact_backup>
      <investigator>
        <last_name>Neal Benowitz, MD</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location_countries>
      <country>United States</country>
    </location_countries>
    <verification_date>July 2023</verification_date>
    <study_first_submitted>July 17, 2023</study_first_submitted>
    <study_first_submitted_qc>July 17, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">July 27, 2023</study_first_posted>
    <last_update_submitted>July 17, 2023</last_update_submitted>
    <last_update_submitted_qc>July 17, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">July 27, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>Nicotine Pharmacokinetics</keyword>
    <keyword>Nicotine Pharmacodynamics</keyword>
    <keyword>Vaping</keyword>
    <keyword>E-cigarettes</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Tobacco Use Disorder</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Nicotine</mesh_term>
    </intervention_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT05962229
  org study id: 22-36348
  secondary id: 1R01DA057282-01
  nct id: NCT05962229
  lead sponsor: 
  collaborator: 
  has dmc: Yes
  is fda regulated drug: Yes
  is fda regulated device: No
  In a crossover study, experienced electronic cigarette users will vape 3 different forms of
        nicotine: natural (derived from tobacco), synthetic, or a 50:50 mixture of both natural and
        synthetic. The investigators will compare nicotine metabolism, cardiovascular effects,
        patterns of self-administration, and participants' feelings of craving/withdrawal and
        enjoyment.
  allocation: Randomized
  intervention model: Crossover Assignment
  intervention model description: Within-subject, single-blinded crossover study. Participants will be randomized to the order of the 3 conditions using a Latin Square design.
  primary purpose: Basic Science
  masking: Single (Participant)
  measure: Mean Nicotine Exposure Over Time
  time frame: Up to 7 hours
  description: Plasma nicotine area under the concentrated time curve (AUC) (ng/ml*h)
  measure: Mean Amount of Nicotine Consumed Over Time
  time frame: 120 minutes
  description: Nicotine self-administration determined by device weight change before and after use multiplied by the nicotine concentration in the e-liquid
  arm group label: S-nicotine (tobacco) as the starting condition
  arm group type: Experimental
  description: Participants will spend 8 hours in the hospital research ward where they will vape e-liquid containing 100% (S)-nicotine.
  arm group label: R-nicotine (synthetic) as the starting condition
  arm group type: Experimental
  description: Participants will spend 8 hours in the hospital research ward where they will vape e-liquid containing 100% (R)-nicotine.
  arm group label: Racemic (50:50 S- and R- nicotine) as the starting condition
  arm group type: Experimental
  description: Participants will spend 8 hours in the hospital research ward where they will vape e-liquid containing 50% (S)-nicotine and 50% (R)-nicotine.
  intervention type: Drug
  intervention name: (S)-Nicotine
  description: Participants will spend 8 hours in the hospital research ward and will vape e-liquid containing 100% (S)-nicotine. They will vape following a standardized session, followed by a 4 hour abstinence period. Participants will then vape as they wish (ad libitum) for 90 minutes.
  arm group label: R-nicotine (synthetic) as the starting condition
  arm group label: Racemic (50:50 S- and R- nicotine) as the starting condition
  arm group label: S-nicotine (tobacco) as the starting condition
  intervention type: Drug
  intervention name: (R)- nicotine
  description: Participants will spend 8 hours in the hospital research ward and will vape e-liquid containing 100% (R)-nicotine. They will vape following a standardized session, followed by a 4 hour abstinence period. Participants will then vape as they wish (ad libitum) for 90 minutes.
  arm group label: R-nicotine (synthetic) as the starting condition
  arm group label: Racemic (50:50 S- and R- nicotine) as the starting condition
  arm group label: S-nicotine (tobacco) as the starting condition
  intervention type: Drug
  intervention name: Racemic nicotine
  description: Participants will spend 8 hours in the hospital research ward and will vape e-liquid containing 50% (R)-nicotine and 50% (S)-nicotine. They will vape following a standardized session, followed by a 4 hour abstinence period. Participants will then vape as they wish (ad libitum) for 90 minutes.
  arm group label: R-nicotine (synthetic) as the starting condition
  arm group label: Racemic (50:50 S- and R- nicotine) as the starting condition
  arm group label: S-nicotine (tobacco) as the starting condition
  other name: 50:50 mixture of (S)- and (R)-nicotine
  criteria: 
  gender: All
  minimum age: 21 Years
  maximum age: 65 Years
  healthy volunteers: Accepts Healthy Volunteers
  last name: Neal Benowitz, MD
  role: Principal Investigator
  affiliation: University of California, San Francisco
  last name: Lisa Lawrence
  phone: 628-206-4204
  email: lisa.lawrence@ucsf.edu
  last name: Armando Barraza
  phone: 510-560-4842
  email: armando.barraza@ucsf.edu
  facility: 
  contact: 
  contact backup: 
  investigator: 
  country: United States
  responsible party type: Sponsor
  mesh term: Tobacco Use Disorder
  mesh term: Nicotine
  sharing ipd: No