<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/NCT03248713</url>
  </required_header>
  <id_info>
    <org_study_id>MS053</org_study_id>
    <nct_id>NCT03248713</nct_id>
  </id_info>
  <brief_title>Glucocorticoid Antagonist Treatment for Tobacco Use Disorder</brief_title>
  <official_title>Glucocorticoid Antagonist Treatment for Tobacco Use Disorder</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>
      The purpose of this protocol is to examine whether mifepristone, a medication with&#xD;
      glucocorticoid receptor antagonist activity, may be a potential treatment for Tobacco Use&#xD;
      Disorder (TUD). Mifepristone has already shown promise as a potential treatment for PTSD (1)&#xD;
      and alcohol use disorder (AUD) (2), but no previous studies have examined the therapeutic&#xD;
      potential of mifepristone for TUD. This will be a double-blind, placebo-controlled study on&#xD;
      the effects of a 7-day treatment with 600 mg mifepristone, or placebo, on cognitive function,&#xD;
      tobacco withdrawal severity, and smoking behavior.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This will be a double-blind, placebo-controlled study that tests the effects of a 7-day&#xD;
      treatment with 600 mg mifepristone, or placebo, on cognitive function, tobacco withdrawal&#xD;
      severity and smoking behavior. Once the intake and physical examination is completed and&#xD;
      eligibility is determined, subjects will participate in a baseline session to become familiar&#xD;
      with the study procedures and to assess baseline measures of withdrawal, smoking urges, pain&#xD;
      sensitivity, and cognitive performance. Subjects will be asked to refrain from consuming&#xD;
      alcoholic beverages and drugs during their study participation. This will be verified by&#xD;
      urine drug screening and breathalyzer before the session and during outpatient visits. If&#xD;
      results indicate non-compliance with these study procedures, subjects will be discharged from&#xD;
      the study.&#xD;
&#xD;
      Participants will be assessed for compliance with medication treatment, withdrawal severity,&#xD;
      recent smoking behavior, and cognitive function during treatment visits on Days 1 and 4. On&#xD;
      Day 7, following overnight abstinence from smoking, participants will attend a test session&#xD;
      that models relapse to smoking. During this session, subjects will have the option to smoke,&#xD;
      or to delay smoking in exchange for monetary compensation (45). To examine if mifepristone's&#xD;
      proposed therapeutic effects last beyond the treatment duration (as observed in previous&#xD;
      studies), there will be 1-week and 1-month follow-up assessments on smoking behavior, urges&#xD;
      to smoke, endocrine biomarkers, and cognitive function.&#xD;
&#xD;
      Participants in each group will complete the laboratory-based, delayed smoking procedure in a&#xD;
      designated, negative pressure room in Bldg. 36 of the West Haven VA just after assessing pain&#xD;
      sensitivity with the cPT. This sequence allows the cPT to assess pain sensitivity, a&#xD;
      potential biomarker of relapse behavior, and to also be used as a mild stressor prior to&#xD;
      participation in the smoking relapse model. Participants will be instructed to abstain from&#xD;
      smoking after 10 pm the night before Test Sessions. Abstinence will be confirmed the morning&#xD;
      of the session by measuring a breath CO level of &lt; 8 ppm.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Lack of recruitment&#xD;
  </why_stopped>
  <start_date type="Actual">November 29, 2017</start_date>
  <completion_date type="Actual">May 20, 2019</completion_date>
  <primary_completion_date type="Actual">May 20, 2019</primary_completion_date>
  <phase>Early 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>The primary analyses will use linear mixed models (LMMs). LMMs can handle continuous and dichotomous outcomes, as well as missing data. Analyses will include baseline (pre-treatment) measures of these variables as covariates and other baseline variables where appropriate.</intervention_model_description>
    <primary_purpose>Health Services Research</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
    <masking_description>This is a double blind randomized study</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Minnesota Nicotine Withdrawal Symptom Checklist (M-NWSC)</measure>
    <time_frame>one week</time_frame>
    <description>Smokers will be asked to rate several nicotine withdrawal symptoms on a 100 mm scale, from &quot;not at all&quot; to &quot;extremely.&quot;</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">8</enrollment>
  <condition>Nicotine Dependence</condition>
  <arm_group>
    <arm_group_label>Mifepristone</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Mifepristone 600 mg/day in 2 tablets</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>matching placebo in 2 tablets</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Mifepristone</intervention_name>
    <description>Mifepristone 600mg 2 tablets will be compared to the placebo</description>
    <arm_group_label>Placebo</arm_group_label>
    <other_name>korlym, mifeprex</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo sugar 2 tablets will be compared to mifepristone</description>
    <arm_group_label>Mifepristone</arm_group_label>
    <other_name>sugar pill</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male smokers aged 18 to 55 years;&#xD;
&#xD;
          -  History of smoking at least 5 cigarettes daily for the past 12 months;&#xD;
&#xD;
          -  In good health as verified by medical history, screening examination, and -screening&#xD;
             laboratory tests&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  History of mifepristone allergy;&#xD;
&#xD;
          -  Requirement of any form of regular psychotropic medication (antidepressants,&#xD;
             antipsychotics, or anxiolytics) and recent psychiatric history (in the past 6 months);&#xD;
&#xD;
          -  Medical illnesses including diabetes, cardiovascular, renal, endocrine, or hepatic&#xD;
             disorders;&#xD;
&#xD;
          -  Prolonged QTc interval &gt;450 msec;&#xD;
&#xD;
          -  History of adrenal insufficiency or a morning plasma cortisol level less than 5 mcg/dl&#xD;
             at screening;&#xD;
&#xD;
          -  Hypokalemia at screening (defined as potassium level &lt; 3.5 mEq/L);&#xD;
&#xD;
          -  Current use of clinically significant CYP 3A4 substrates including, simvastatin,&#xD;
             lovastatin, cyclosporine, ergotamines, fentanyl, pimozide, quinidine, sirolimus,&#xD;
             tacrolimus, triazolam, midazolam.&#xD;
&#xD;
          -  use of rifapentin, phenobarbital, phenytoin, carbamazepine, and St. John's Wort.&#xD;
&#xD;
          -  Current use of strong 3A4 inhibitors including ketoconazole, itraconazole, nefazodone,&#xD;
             ritonavir, nelfinavir, indinavir, atazanavir, amprenavir, fosamprenivir, boceprevir,&#xD;
             clarithromycin, conivaptan, lopinavir, mibefradil, posaconazole, saquinavir,&#xD;
             telaprevir, telithromycin, voriconazole.&#xD;
&#xD;
          -  Treatment with systemic corticosteroids&#xD;
&#xD;
          -  Current use of clinically significant CYP 3A inducers (e.g., rifampin, rifabutin);&#xD;
&#xD;
          -  Abuse of alcohol or any other illicit or prescription drugs;&#xD;
&#xD;
          -  Inability to tolerate cold exposure due to conditions such as peripheral -vascular&#xD;
             disease or Raynaud's phenomenon;&#xD;
&#xD;
          -  Inability to fulfill all scheduled visits and examination procedures throughout the&#xD;
             study period.&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <gender_based>Yes</gender_based>
    <gender_description>Male smokers</gender_description>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>55 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>May 2019</verification_date>
  <study_first_submitted>August 4, 2017</study_first_submitted>
  <study_first_submitted_qc>August 11, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 14, 2017</study_first_posted>
  <last_update_submitted>May 23, 2019</last_update_submitted>
  <last_update_submitted_qc>May 23, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">May 28, 2019</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>Mifepristone</mesh_term>
  </intervention_browse>
  <!-- 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/NCT03248713
org study id: MS053
nct id: NCT03248713
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
The purpose of this protocol is to examine whether mifepristone, a medication with
      glucocorticoid receptor antagonist activity, may be a potential treatment for Tobacco Use
      Disorder (TUD). Mifepristone has already shown promise as a potential treatment for PTSD (1)
      and alcohol use disorder (AUD) (2), but no previous studies have examined the therapeutic
      potential of mifepristone for TUD. This will be a double-blind, placebo-controlled study on
      the effects of a 7-day treatment with 600 mg mifepristone, or placebo, on cognitive function,
      tobacco withdrawal severity, and smoking behavior.
This will be a double-blind, placebo-controlled study that tests the effects of a 7-day
      treatment with 600 mg mifepristone, or placebo, on cognitive function, tobacco withdrawal
      severity and smoking behavior. Once the intake and physical examination is completed and
      eligibility is determined, subjects will participate in a baseline session to become familiar
      with the study procedures and to assess baseline measures of withdrawal, smoking urges, pain
      sensitivity, and cognitive performance. Subjects will be asked to refrain from consuming
      alcoholic beverages and drugs during their study participation. This will be verified by
      urine drug screening and breathalyzer before the session and during outpatient visits. If
      results indicate non-compliance with these study procedures, subjects will be discharged from
      the study.

      Participants will be assessed for compliance with medication treatment, withdrawal severity,
      recent smoking behavior, and cognitive function during treatment visits on Days 1 and 4. On
      Day 7, following overnight abstinence from smoking, participants will attend a test session
      that models relapse to smoking. During this session, subjects will have the option to smoke,
      or to delay smoking in exchange for monetary compensation (45). To examine if mifepristone's
      proposed therapeutic effects last beyond the treatment duration (as observed in previous
      studies), there will be 1-week and 1-month follow-up assessments on smoking behavior, urges
      to smoke, endocrine biomarkers, and cognitive function.

      Participants in each group will complete the laboratory-based, delayed smoking procedure in a
      designated, negative pressure room in Bldg. 36 of the West Haven VA just after assessing pain
      sensitivity with the cPT. This sequence allows the cPT to assess pain sensitivity, a
      potential biomarker of relapse behavior, and to also be used as a mild stressor prior to
      participation in the smoking relapse model. Participants will be instructed to abstain from
      smoking after 10 pm the night before Test Sessions. Abstinence will be confirmed the morning
      of the session by measuring a breath CO level of < 8 ppm.
allocation: Randomized
intervention model: Crossover Assignment
intervention model description: The primary analyses will use linear mixed models (LMMs). LMMs can handle continuous and dichotomous outcomes, as well as missing data. Analyses will include baseline (pre-treatment) measures of these variables as covariates and other baseline variables where appropriate.
primary purpose: Health Services Research
masking: Double (Participant, Investigator)
masking description: This is a double blind randomized study
measure: Minnesota Nicotine Withdrawal Symptom Checklist (M-NWSC)
time frame: one week
description: Smokers will be asked to rate several nicotine withdrawal symptoms on a 100 mm scale, from "not at all" to "extremely."
arm group label: Mifepristone
arm group type: Active Comparator
description: Mifepristone 600 mg/day in 2 tablets
arm group label: Placebo
arm group type: Placebo Comparator
description: matching placebo in 2 tablets
intervention type: Drug
intervention name: Mifepristone
description: Mifepristone 600mg 2 tablets will be compared to the placebo
arm group label: Placebo
other name: korlym, mifeprex
intervention type: Drug
intervention name: Placebo
description: Placebo sugar 2 tablets will be compared to mifepristone
arm group label: Mifepristone
other name: sugar pill
criteria: 
gender: Male
gender based: Yes
gender description: Male smokers
minimum age: 18 Years
maximum age: 55 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: Sponsor
mesh term: Tobacco Use Disorder
mesh term: Mifepristone