<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/NCT03813121</url>
  </required_header>
  <id_info>
    <org_study_id>IRB000229077</org_study_id>
    <nct_id>NCT03813121</nct_id>
  </id_info>
  <brief_title>The Effects of Sedatives on Tobacco Use Disorder</brief_title>
  <acronym>SED-TUD</acronym>
  <official_title>The Effects of Sedatives on Tobacco Use Disorder</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Wake Forest University Health Sciences</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Wake Forest University Health Sciences</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This proposal will obtain preliminary data on the effect of a single sub-anesthetic dose of a&#xD;
      sedative on cigarette craving and smoking behavior as well as measuring tolerability and&#xD;
      acceptability.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 1, 2019</start_date>
  <completion_date type="Actual">August 31, 2021</completion_date>
  <primary_completion_date type="Actual">August 31, 2021</primary_completion_date>
  <phase>Phase 1/Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>Single (Participant)</masking>
    <masking_description>single-blind</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Side Effects</measure>
    <time_frame>about 1 week post infusion</time_frame>
    <description>drug side effects scale: severity scale from 1 (not at all) to 7 (extremely) for symptoms of nausea, dizziness, sleepiness, strange thoughts, hallucinations, confusion, anxiousness, and headache. The average score across all side effects is reported.</description>
  </primary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">10</enrollment>
  <condition>Tobacco Use Disorder</condition>
  <arm_group>
    <arm_group_label>midazolam intravenous infusion</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>single midazolam infusion (0.02 mg/kg over 20 minutes)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>placebo intravenous infusion</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>single placebo infusion (saline over 20 minutes)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>ketamine intravenous infusion</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>single ketamine infusion (0.5 mg/kg over 20 minutes)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>midazolam intravenous infusion</intervention_name>
    <description>Participants will receive a single drug infusion</description>
    <arm_group_label>midazolam intravenous infusion</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>placebo intravenous infusion</intervention_name>
    <description>Participants will receive a single placebo infusion</description>
    <arm_group_label>placebo intravenous infusion</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>ketamine intravenous infusion</intervention_name>
    <description>Participants will receive a single drug infusion</description>
    <arm_group_label>ketamine intravenous infusion</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  smoke at least 5 cigarettes per day&#xD;
&#xD;
          -  smoked at least 2 years&#xD;
&#xD;
          -  negative urine drug screen for psychoactive drugs and negative breath alcohol&#xD;
             concentration&#xD;
&#xD;
          -  live in Little Rock AR or surrounding area&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  unstable or stable medical condition that would interact with study medication or&#xD;
             participation&#xD;
&#xD;
          -  serious head trauma or neurological disorder&#xD;
&#xD;
          -  hypertension, abnormal ECG or metabolic blood results&#xD;
&#xD;
          -  meet criteria for psychosis, schizophrenia, major depressive disorder, or bipolar&#xD;
             disorder&#xD;
&#xD;
          -  use of psychoactive drugs or medications&#xD;
&#xD;
          -  BMI &gt; 40&#xD;
&#xD;
          -  among women, pregnancy or breastfeeding&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>55 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Merideth Addicott, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Arkansas</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Arkansas for Medical Sciences</name>
      <address>
        <city>Little Rock</city>
        <state>Arkansas</state>
        <zip>72205</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2022</verification_date>
  <study_first_submitted>January 18, 2019</study_first_submitted>
  <study_first_submitted_qc>January 22, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 23, 2019</study_first_posted>
  <results_first_submitted>April 11, 2022</results_first_submitted>
  <results_first_submitted_qc>June 1, 2022</results_first_submitted_qc>
  <results_first_posted type="Actual">June 2, 2022</results_first_posted>
  <last_update_submitted>September 28, 2022</last_update_submitted>
  <last_update_submitted_qc>September 28, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">October 6, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <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>Midazolam</mesh_term>
    <mesh_term>Ketamine</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>March 2, 2021</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/21/NCT03813121/Prot_SAP_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Informed Consent Form</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>January 15, 2021</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/21/NCT03813121/ICF_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>Participants must be screened for eligibility before being assigned to a group. Participants deemed ineligible were excluded from the study.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Placebo Intravenous Infusion</title>
          <description>single placebo infusion (saline over 20 minutes)&#xD;
placebo intravenous infusion: Participants will receive a single placebo infusion</description>
        </group>
        <group group_id="P2">
          <title>Ketamine Intravenous Infusion</title>
          <description>single ketamine infusion (0.5 mg/kg over 20 minutes)&#xD;
ketamine intravenous infusion: Participants will receive a single drug infusion</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="6"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="6"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Placebo Intravenous Infusion</title>
          <description>single placebo infusion (saline over 20 minutes)&#xD;
placebo intravenous infusion: Participants will receive a single placebo infusion</description>
        </group>
        <group group_id="B2">
          <title>Ketamine Intravenous Infusion</title>
          <description>single ketamine infusion (0.5 mg/kg over 20 minutes)&#xD;
ketamine intravenous infusion: Participants will receive a single drug infusion</description>
        </group>
        <group group_id="B3">
          <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="4"/>
            <count group_id="B2" value="6"/>
            <count group_id="B3" value="10"/>
          </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="37.5" spread="11.2"/>
                    <measurement group_id="B2" value="35.5" spread="15.4"/>
                    <measurement group_id="B3" value="36.3" spread="13.2"/>
                  </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="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="6"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Side Effects</title>
        <description>drug side effects scale: severity scale from 1 (not at all) to 7 (extremely) for symptoms of nausea, dizziness, sleepiness, strange thoughts, hallucinations, confusion, anxiousness, and headache. The average score across all side effects is reported.</description>
        <time_frame>about 1 week post infusion</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Placebo Intravenous Infusion</title>
            <description>single placebo infusion (saline over 20 minutes)&#xD;
placebo intravenous infusion: Participants will receive a single placebo infusion</description>
          </group>
          <group group_id="O2">
            <title>Ketamine Intravenous Infusion</title>
            <description>single ketamine infusion (0.5 mg/kg over 20 minutes)&#xD;
ketamine intravenous infusion: Participants will receive a single drug infusion</description>
          </group>
        </group_list>
        <measure>
          <title>Side Effects</title>
          <description>drug side effects scale: severity scale from 1 (not at all) to 7 (extremely) for symptoms of nausea, dizziness, sleepiness, strange thoughts, hallucinations, confusion, anxiousness, and headache. The average score across all side effects is reported.</description>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="4"/>
                <count group_id="O2" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.3" spread="0.2"/>
                    <measurement group_id="O2" value="1.4" spread="0.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>For 7 days post drug administration.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Placebo Intravenous Infusion</title>
          <description>single placebo infusion (saline over 20 minutes)&#xD;
placebo intravenous infusion: Participants will receive a single placebo infusion</description>
        </group>
        <group group_id="E2">
          <title>Ketamine Intravenous Infusion</title>
          <description>single ketamine infusion (0.5 mg/kg over 20 minutes)&#xD;
ketamine intravenous infusion: Participants will receive a single drug infusion</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="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Emotional distress</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>motor incoordination</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Tingling</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE 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>
    <limitations_and_caveats>The planned enrollment was 12 people. Investigator decided to complete the study early at 10 people because the principal investigator was leaving the institution and the logistics of running this remotely were too difficult. The last participant's last visit occurred, no new subjects were enrolled</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Dr. Merideth Addicott</name_or_title>
      <organization>Wake Forest University School of Medicine</organization>
      <phone>336-716-7792</phone>
      <email>maddicot@wakehealth.edu</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/NCT03813121
org study id: IRB000229077
nct id: NCT03813121
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
This proposal will obtain preliminary data on the effect of a single sub-anesthetic dose of a
      sedative on cigarette craving and smoking behavior as well as measuring tolerability and
      acceptability.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Basic Science
masking: Single (Participant)
masking description: single-blind
measure: Side Effects
time frame: about 1 week post infusion
description: drug side effects scale: severity scale from 1 (not at all) to 7 (extremely) for symptoms of nausea, dizziness, sleepiness, strange thoughts, hallucinations, confusion, anxiousness, and headache. The average score across all side effects is reported.
arm group label: midazolam intravenous infusion
arm group type: Experimental
description: single midazolam infusion (0.02 mg/kg over 20 minutes)
arm group label: placebo intravenous infusion
arm group type: Placebo Comparator
description: single placebo infusion (saline over 20 minutes)
arm group label: ketamine intravenous infusion
arm group type: Experimental
description: single ketamine infusion (0.5 mg/kg over 20 minutes)
intervention type: Drug
intervention name: midazolam intravenous infusion
description: Participants will receive a single drug infusion
arm group label: midazolam intravenous infusion
intervention type: Drug
intervention name: placebo intravenous infusion
description: Participants will receive a single placebo infusion
arm group label: placebo intravenous infusion
intervention type: Drug
intervention name: ketamine intravenous infusion
description: Participants will receive a single drug infusion
arm group label: ketamine intravenous infusion
criteria: 
gender: All
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Merideth Addicott, PhD
role: Principal Investigator
affiliation: University of Arkansas
facility: 
country: United States
responsible party type: Sponsor
mesh term: Tobacco Use Disorder
mesh term: Midazolam
mesh term: Ketamine
sharing ipd: No
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: The planned enrollment was 12 people. Investigator decided to complete the study early at 10 people because the principal investigator was leaving the institution and the logistics of running this remotely were too difficult. The last participant's last visit occurred, no new subjects were enrolled
point of contact: 