<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/NCT04488744</url>
  </required_header>
  <id_info>
    <org_study_id>MS059</org_study_id>
    <nct_id>NCT04488744</nct_id>
  </id_info>
  <brief_title>Smoking by IV Pulsed Nicotine</brief_title>
  <official_title>Modeling Tobacco Smoking by IV Pulsed Nicotine in Smokers</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Yale University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Yale University</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>
      To establish a dose-effect curve for nicotine's abuse potential as a function of nicotine&#xD;
      dose and delivery rate. Pulsed IV nicotine administration will be used as it closely matches&#xD;
      nicotine delivery by inhaled tobacco use.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Both sub-studies will enroll male and female tobacco cigarette smokers. This study will&#xD;
      examine the feasibility of the proposed study parameters in a total of 10 completers. In a&#xD;
      crossover design, participants will be tested under 5 conditions: 0.2 mg nicotine delivered&#xD;
      over 2.5 minutes (5 pulsed-nicotine deliveries), 0.2mg nicotine delivered over 10 min (20&#xD;
      pulsed-nicotine deliveries), 1.0 mg nicotine delivered over 2.5 minutes (5 pulsed-nicotine&#xD;
      deliveries) and 1.0 mg nicotine delivered over 10 min (20 pulsed-nicotine deliveries). The&#xD;
      main outcome measures will be self-report drug effects and urges to smoke cigarettes.&#xD;
&#xD;
      The investigators hypothesize that the abuse potential and alleviation of smoking urges are&#xD;
      produced by nicotine as a function of nicotine dose and delivery rate.&#xD;
&#xD;
      This study is complete with 13 enrolled and 10 completers&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 15, 2019</start_date>
  <completion_date type="Actual">May 31, 2021</completion_date>
  <primary_completion_date type="Actual">April 28, 2021</primary_completion_date>
  <phase>Early Phase 1</phase>
  <study_type>Interventional</study_type>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <intervention_model_description>placebo-controlled, mixed-design with nicotine dose as a between-subject and nicotine delivery rate as a within-subject factor.</intervention_model_description>
    <primary_purpose>Health Services Research</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
    <masking_description>Participant will not know nicotine dose or rate of infusion.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Heart rate will be used to see the dose effect</measure>
    <time_frame>During nicotine infusion max of ten minutes</time_frame>
    <description>the dose-effect curves of nicotine dose and delivery rate in heart rate</description>
  </primary_outcome>
  <number_of_arms>5</number_of_arms>
  <enrollment type="Actual">13</enrollment>
  <condition>Smoking Cessation</condition>
  <arm_group>
    <arm_group_label>nicotine infusion 0.2mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>nicotine infusion&#xD;
0.2 mg nicotine delivered over 2.5 minutes (5 pulsed-nicotine deliveries) The day order will be randomized over 5 days.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>nicotine infusion 2.0mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>0.2mg nicotine delivered over 10 min (20 pulsed-nicotine deliveries),</description>
  </arm_group>
  <arm_group>
    <arm_group_label>nicotine infusion 1.0mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>1.0 mg nicotine delivered over 2.5 minutes (5 pulsed-nicotine deliveries)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>nicotine infuison 1.0mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>1.0 mg nicotine delivered over 10 min (20 pulsed-nicotine deliveries).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Saline</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>saline delivered over 2minutes ,2.5minutes,10 minutes</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Nicotine 0.2mcg/kg/s and 1.0mcg/kg/s</intervention_name>
    <description>Nicotine infusion 0.2 mg nicotine delivered over 2.5 minutes (5 pulsed-nicotine deliveries), 0.2mg nicotine delivered over 10 min (20 pulsed-nicotine deliveries), 1.0 mg nicotine delivered over 2.5 minutes (5 pulsed-nicotine deliveries) and 1.0 mg nicotine delivered over 10 min (20 pulsed-nicotine deliveries).</description>
    <arm_group_label>Saline</arm_group_label>
    <arm_group_label>nicotine infuison 1.0mg</arm_group_label>
    <arm_group_label>nicotine infusion 0.2mg</arm_group_label>
    <arm_group_label>nicotine infusion 1.0mg</arm_group_label>
    <arm_group_label>nicotine infusion 2.0mg</arm_group_label>
    <other_name>nicotine infusion</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Female and male smokers, aged 18 to 35 years, who have been smoking tobacco cigarettes&#xD;
             for at least a year&#xD;
&#xD;
          -  smoke ≥ 5 and less than 20 cigarettes per day&#xD;
&#xD;
          -  urine cotinine levels &gt; 100 ng/mL consistent with nicotine intake of an active smoker&#xD;
&#xD;
          -  not seeking treatment at the time of the study for nicotine dependence&#xD;
&#xD;
          -  in good health as verified by medical history, screening examination, and screening&#xD;
             laboratory tests; and 6) for women, not pregnant as determined by pregnancy screening,&#xD;
             nor breast feeding, and using acceptable birth control methods.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  History of major medical or psychiatric disorders that the physician investigator&#xD;
             deems as contraindicated for the subject to be in the study&#xD;
&#xD;
          -  regular use of psychotropic medication (antidepressants, antipsychotics, or&#xD;
             anxiolytics)&#xD;
&#xD;
          -  current alcohol or substance dependence for any other recreational or prescription&#xD;
             drugs other than nicotine&#xD;
&#xD;
          -  use of e-cigarettes more than 10 days in the past 30 days&#xD;
&#xD;
          -  urine drug screening indicating recent illicit drugs use (with the exception of&#xD;
             marijuana)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>35 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Mehmet Sofuoglu, M.D.,Ph.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Yale University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Veterans Affairs Hospital</name>
      <address>
        <city>West Haven</city>
        <state>Connecticut</state>
        <zip>06516</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>July 2021</verification_date>
  <study_first_submitted>July 23, 2020</study_first_submitted>
  <study_first_submitted_qc>July 23, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 28, 2020</study_first_posted>
  <last_update_submitted>July 13, 2021</last_update_submitted>
  <last_update_submitted_qc>July 13, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">July 20, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Yale University</investigator_affiliation>
    <investigator_full_name>Mehmet Sofuoglu</investigator_full_name>
    <investigator_title>Professor of Psychiatry</investigator_title>
  </responsible_party>
  <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>


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/NCT04488744
org study id: MS059
nct id: NCT04488744
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
To establish a dose-effect curve for nicotine's abuse potential as a function of nicotine
      dose and delivery rate. Pulsed IV nicotine administration will be used as it closely matches
      nicotine delivery by inhaled tobacco use.
Both sub-studies will enroll male and female tobacco cigarette smokers. This study will
      examine the feasibility of the proposed study parameters in a total of 10 completers. In a
      crossover design, participants will be tested under 5 conditions: 0.2 mg nicotine delivered
      over 2.5 minutes (5 pulsed-nicotine deliveries), 0.2mg nicotine delivered over 10 min (20
      pulsed-nicotine deliveries), 1.0 mg nicotine delivered over 2.5 minutes (5 pulsed-nicotine
      deliveries) and 1.0 mg nicotine delivered over 10 min (20 pulsed-nicotine deliveries). The
      main outcome measures will be self-report drug effects and urges to smoke cigarettes.

      The investigators hypothesize that the abuse potential and alleviation of smoking urges are
      produced by nicotine as a function of nicotine dose and delivery rate.

      This study is complete with 13 enrolled and 10 completers
allocation: Randomized
intervention model: Crossover Assignment
intervention model description: placebo-controlled, mixed-design with nicotine dose as a between-subject and nicotine delivery rate as a within-subject factor.
primary purpose: Health Services Research
masking: Double (Participant, Investigator)
masking description: Participant will not know nicotine dose or rate of infusion.
measure: Heart rate will be used to see the dose effect
time frame: During nicotine infusion max of ten minutes
description: the dose-effect curves of nicotine dose and delivery rate in heart rate
arm group label: nicotine infusion 0.2mg
arm group type: Experimental
description: nicotine infusion
0.2 mg nicotine delivered over 2.5 minutes (5 pulsed-nicotine deliveries) The day order will be randomized over 5 days.
arm group label: nicotine infusion 2.0mg
arm group type: Experimental
description: 0.2mg nicotine delivered over 10 min (20 pulsed-nicotine deliveries),
arm group label: nicotine infusion 1.0mg
arm group type: Experimental
description: 1.0 mg nicotine delivered over 2.5 minutes (5 pulsed-nicotine deliveries)
arm group label: nicotine infuison 1.0mg
arm group type: Experimental
description: 1.0 mg nicotine delivered over 10 min (20 pulsed-nicotine deliveries).
arm group label: Saline
arm group type: Placebo Comparator
description: saline delivered over 2minutes ,2.5minutes,10 minutes
intervention type: Drug
intervention name: Nicotine 0.2mcg/kg/s and 1.0mcg/kg/s
description: Nicotine infusion 0.2 mg nicotine delivered over 2.5 minutes (5 pulsed-nicotine deliveries), 0.2mg nicotine delivered over 10 min (20 pulsed-nicotine deliveries), 1.0 mg nicotine delivered over 2.5 minutes (5 pulsed-nicotine deliveries) and 1.0 mg nicotine delivered over 10 min (20 pulsed-nicotine deliveries).
arm group label: Saline
arm group label: nicotine infuison 1.0mg
arm group label: nicotine infusion 0.2mg
arm group label: nicotine infusion 1.0mg
arm group label: nicotine infusion 2.0mg
other name: nicotine infusion
criteria: 
gender: All
minimum age: 18 Years
maximum age: 35 Years
healthy volunteers: No
last name: Mehmet Sofuoglu, M.D.,Ph.D.
role: Principal Investigator
affiliation: Yale University
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Yale University
investigator full name: Mehmet Sofuoglu
investigator title: Professor of Psychiatry
mesh term: Nicotine
sharing ipd: No