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/NCT06014385</url>
    </required_header>
    <id_info>
      <org_study_id>2000034723</org_study_id>
      <nct_id>NCT06014385</nct_id>
    </id_info>
    <brief_title>PET and MRI Imaging With Scopolamine at the Muscarinic M1 Receptor</brief_title>
    <acronym>emo_to2</acronym>
    <official_title>A Trial to Evaluate Target Occupancy of Scopolamine at the Muscarinic M1 Receptor</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Yale University</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>Janssen Scientific Affairs, LLC</agency>
        <agency_class>Industry</agency_class>
      </collaborator>
    </sponsors>
    <source>Yale University</source>
    <oversight_info>
      <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 study is to assess the target occupancy (TO) of scopolamine at M1&#xD;
        Muscarinic Receptors in the brain after single I.V. doses of scopolamine, in healthy control&#xD;
        subjects, using the radiotracer [11C]EMO (also known as [11C]LSN3172176).&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Each participant will complete a baseline (pre-dose) PET scan and a post-dose PET scan,&#xD;
        following a 15-minute IV infusion of scopolamine. Each participant will also complete a&#xD;
        magnetic resonance imaging (MRI) scan of the brain. The timing of the post scopolamine [11C]&#xD;
        EMO PET scan tracer injection could occur 15 minutes to 48 hours after the scopolamine&#xD;
        infusion has been completed.&#xD;
  &#xD;
        In this study, the post scopolamine [11C] EMO PET scan tracer injection should be given 4&#xD;
        hours (± 5 minutes) after the scopolamine infusion of 4.0 μg/kg in up to 2 subjects. The data&#xD;
        from those 2 subjects will be reviewed to determine the timepoint for tracer injection for&#xD;
        the post scopolamine [11C] EMO PET scan in the next 2 subjects (e.g., tracer injection at&#xD;
        24-hour or 1-hour post-dose). If the baseline and post scopolamine PET scans are obtained on&#xD;
        the same day, the scopolamine infusion should be started after the acquisition of the&#xD;
        baseline PET scan has been completed. The data from the first 4 subjects will be reviewed to&#xD;
        determine the dose level and timepoint for tracer injection in the last 2 subjects. . At&#xD;
        least 2 hours should elapse between injections of [11C] EMO to allow for clearance of the&#xD;
        tracer signal from the baseline scan and the injection of [11C] EMO for a post scopolamine&#xD;
        PET scan should not be given during a scopolamine infusion. Participants will complete at&#xD;
        least 2 visits and up to 4.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">October 1, 2023</start_date>
    <completion_date type="Anticipated">October 1, 2024</completion_date>
    <primary_completion_date type="Anticipated">October 1, 2024</primary_completion_date>
    <phase>Phase 1</phase>
    <study_type>Interventional</study_type>
    <study_design_info>
      <allocation>Non-Randomized</allocation>
      <intervention_model>Parallel Assignment</intervention_model>
      <primary_purpose>Basic Science</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Change in brain muscarinic receptor occupancy with [11C]LSN3172176 PET</measure>
      <time_frame>baseline and up to 48 hours post scopolamine infusion</time_frame>
      <description>M1 Muscarinic receptor occupancy in the brain following a 15-minute IV infusion of scopolamine in healthy adult participants using PET scans.</description>
    </primary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">6</enrollment>
    <condition>Muscarinic Receptor Occupancy</condition>
    <arm_group>
      <arm_group_label>Scopolamine high dose</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>The target occupancy (TO) of scopolamine at M1 will be evaluated using the radiotracer [11C]EMO and positron emission tomography (PET). TO will be measured following a 15-minute IV infusion of 4.0 μg/kg scopolamine in 4-6 anticipated participants.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Scopolamine low dose</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>The target occupancy (TO) of scopolamine at M1 will be evaluated using the radiotracer [11C]EMO and positron emission tomography (PET). TO will be measured following a 15-minute IV infusion of 2.0 μg/kg scopolamine in 0-2 anticipated participants.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Scopolamine</intervention_name>
      <description>TO will be measured following a 15-minute IV infusion of up to 2 dose levels of scopolamine: 4.0 μg/kg and 2.0 μg/kg</description>
      <arm_group_label>Scopolamine high dose</arm_group_label>
      <arm_group_label>Scopolamine low dose</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Radiation</intervention_type>
      <intervention_name>[11C]EMO ([11C]LSN3172176)</intervention_name>
      <description>A radiotracer specific for imaging M1 receptors. For each PET scan, up to 20 mCi of [11C]EMO i.v. will be administered twice, at baseline and post dosing with scopolamine.</description>
      <arm_group_label>Scopolamine high dose</arm_group_label>
      <arm_group_label>Scopolamine low dose</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Willing and able to give voluntary, written informed consent&#xD;
  &#xD;
            -  Have the ability to read and write, communicate effectively with the investigator and&#xD;
               to comply with all study requirements, restrictions, and directions of the research&#xD;
               staff.&#xD;
  &#xD;
            -  Male or female, aged Age 18 to 60 years inclusive, at screening.&#xD;
  &#xD;
            -  In good general health as evidenced by medical history, physical examination, ECG,&#xD;
               serum/urine biochemistry, hematology, and serology tests.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  History or presence of clinically significant respiratory, GI, renal, hepatic,&#xD;
               pancreatic, hematological, neurological (including history of seizure),&#xD;
               cardiovascular, psychiatric (including known addictive disorders), musculoskeletal,&#xD;
               genitourinary, immunological, or dermatological disorders, including all cancers.&#xD;
  &#xD;
            -  Laboratory tests with clinically significant abnormalities or positive urine&#xD;
               toxicology, at screening.&#xD;
  &#xD;
            -  Abnormal and clinically significant ECG, as (as determined by the Investigator or&#xD;
               his/her designee) at screening.&#xD;
  &#xD;
            -  Seropositive for hepatitis B, hepatitis C, and/or HIV&#xD;
  &#xD;
            -  Pregnancy or lactation&#xD;
  &#xD;
            -  Use of prescription medications within 14 days of scopolamine dosing. Exceptions may&#xD;
               be allowed only if the medication's administration is deemed unlikely to impact the&#xD;
               study result.&#xD;
  &#xD;
            -  Current or recent use (within 14 days) of scopolamine transdermal patch, for any&#xD;
               reason (ex: for motion sickness).&#xD;
  &#xD;
            -  Use of drugs with anticholinergic properties within 14 days of scopolamine dosing, for&#xD;
               example, belladonna alkaloids, first generation antihistamines, antidepressants&#xD;
               (tricyclics and MAO inhibitors), phenothiazines and second generation antipsychotics&#xD;
               (clozapine and olanzapine), amantadine and quinidine. Non-sedating antihistamines&#xD;
               (e.g., loratadine) use is acceptable.&#xD;
  &#xD;
            -  Strong CYP3A4 inhibitors such as itraconazole and grapefruit juice should also not be&#xD;
               taken within 14 days of receiving scopolamine. Use of CYP3A4 inducers (e.g.,&#xD;
               carbamazepine, rifampin) should not be taken within 21 days of scopolamine&#xD;
               administration.&#xD;
  &#xD;
            -  Treatment with another investigational drug or other intervention within 30 days of&#xD;
               the screening visit, or participation in another trial involving radiotracer&#xD;
               administration within 1 week of dosing day.&#xD;
  &#xD;
            -  Current smoker (including any form of nicotine use)&#xD;
  &#xD;
            -  History of alcohol or drug abuse, within 2 years prior to screening, as determined by&#xD;
               the investigator.&#xD;
  &#xD;
            -  Positive drug test at screening&#xD;
  &#xD;
            -  Blood donation within eight weeks of the start of the study. Subjects that confirm&#xD;
               recent blood donation may reschedule for a later screening date.&#xD;
  &#xD;
            -  History of a bleeding disorder or are currently taking anticoagulants (such as&#xD;
               Coumadin, Heparin, Pradaxa, Xarelto).&#xD;
  &#xD;
            -  Unable to safely discontinue or hold aspirin and other NSAID use, as outlined in&#xD;
               Section 6.1.8&#xD;
  &#xD;
            -  MRI incompatible implants (i.e., such as pacemaker, artificial joints, non-removable&#xD;
               body piercings) and other contraindications for MRI, such as claustrophobia, having&#xD;
               implanted or embedded metal objects/fragments or fragments in the head or body that&#xD;
               would present a risk during the MRI scanning procedure, or have worked with ferrous&#xD;
               metals either as a vocation or hobby (for example, as a sheet metal worker, welder, or&#xD;
               machinist).&#xD;
  &#xD;
            -  Participation in other research studies involving ionizing radiation within one year&#xD;
               of the PET scans that would cause the subject to exceed the yearly dose limits for&#xD;
               healthy volunteers set by the Yale University PET Center. This limit follows the&#xD;
               guidelines listed in 21 CFR 361.1 for research subjects.&#xD;
  &#xD;
            -  Subjects with a history of IV drug use that would prevent venous access for PET tracer&#xD;
               injection.&#xD;
  &#xD;
            -  Subject who has current, past, or anticipated exposure to radiation in the work place&#xD;
               within one year of the proposed research scans that in combination with the study&#xD;
               tracer would result in a cumulative exposure that exceeds recommended exposure limits.&#xD;
  &#xD;
            -  Has any condition that, in the opinion of the investigator, would prevent compliance&#xD;
               with the study protocol.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>N/A</maximum_age>
      <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>David Matuskey, MD</last_name>
      <role>Principal Investigator</role>
      <affiliation>Yale University</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Mark F Dias, MA</last_name>
      <phone>(203) 737-6128</phone>
      <email>mark.dias@yale.edu</email>
    </overall_contact>
    <location>
      <facility>
        <name>Yale University</name>
        <address>
          <city>New Haven</city>
          <state>Connecticut</state>
          <zip>06520</zip>
          <country>United States</country>
        </address>
      </facility>
    </location>
    <location_countries>
      <country>United States</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 22, 2023</study_first_submitted>
    <study_first_submitted_qc>August 22, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 28, 2023</study_first_posted>
    <last_update_submitted>August 31, 2023</last_update_submitted>
    <last_update_submitted_qc>August 31, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 6, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Yale University</investigator_affiliation>
      <investigator_full_name>David Matuskey</investigator_full_name>
      <investigator_title>Associate Professor</investigator_title>
    </responsible_party>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Scopolamine</mesh_term>
      <mesh_term>Butylscopolammonium Bromide</mesh_term>
      <mesh_term>LSN3172176</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/NCT06014385
  org study id: 2000034723
  nct id: NCT06014385
  lead sponsor: 
  collaborator: 
  is fda regulated drug: Yes
  is fda regulated device: No
  The purpose of this study is to assess the target occupancy (TO) of scopolamine at M1
        Muscarinic Receptors in the brain after single I.V. doses of scopolamine, in healthy control
        subjects, using the radiotracer [11C]EMO (also known as [11C]LSN3172176).
  Each participant will complete a baseline (pre-dose) PET scan and a post-dose PET scan,
        following a 15-minute IV infusion of scopolamine. Each participant will also complete a
        magnetic resonance imaging (MRI) scan of the brain. The timing of the post scopolamine [11C]
        EMO PET scan tracer injection could occur 15 minutes to 48 hours after the scopolamine
        infusion has been completed.
  
        In this study, the post scopolamine [11C] EMO PET scan tracer injection should be given 4
        hours (± 5 minutes) after the scopolamine infusion of 4.0 μg/kg in up to 2 subjects. The data
        from those 2 subjects will be reviewed to determine the timepoint for tracer injection for
        the post scopolamine [11C] EMO PET scan in the next 2 subjects (e.g., tracer injection at
        24-hour or 1-hour post-dose). If the baseline and post scopolamine PET scans are obtained on
        the same day, the scopolamine infusion should be started after the acquisition of the
        baseline PET scan has been completed. The data from the first 4 subjects will be reviewed to
        determine the dose level and timepoint for tracer injection in the last 2 subjects. . At
        least 2 hours should elapse between injections of [11C] EMO to allow for clearance of the
        tracer signal from the baseline scan and the injection of [11C] EMO for a post scopolamine
        PET scan should not be given during a scopolamine infusion. Participants will complete at
        least 2 visits and up to 4.
  allocation: Non-Randomized
  intervention model: Parallel Assignment
  primary purpose: Basic Science
  masking: None (Open Label)
  measure: Change in brain muscarinic receptor occupancy with [11C]LSN3172176 PET
  time frame: baseline and up to 48 hours post scopolamine infusion
  description: M1 Muscarinic receptor occupancy in the brain following a 15-minute IV infusion of scopolamine in healthy adult participants using PET scans.
  arm group label: Scopolamine high dose
  arm group type: Experimental
  description: The target occupancy (TO) of scopolamine at M1 will be evaluated using the radiotracer [11C]EMO and positron emission tomography (PET). TO will be measured following a 15-minute IV infusion of 4.0 μg/kg scopolamine in 4-6 anticipated participants.
  arm group label: Scopolamine low dose
  arm group type: Experimental
  description: The target occupancy (TO) of scopolamine at M1 will be evaluated using the radiotracer [11C]EMO and positron emission tomography (PET). TO will be measured following a 15-minute IV infusion of 2.0 μg/kg scopolamine in 0-2 anticipated participants.
  intervention type: Drug
  intervention name: Scopolamine
  description: TO will be measured following a 15-minute IV infusion of up to 2 dose levels of scopolamine: 4.0 μg/kg and 2.0 μg/kg
  arm group label: Scopolamine high dose
  arm group label: Scopolamine low dose
  intervention type: Radiation
  intervention name: [11C]EMO ([11C]LSN3172176)
  description: A radiotracer specific for imaging M1 receptors. For each PET scan, up to 20 mCi of [11C]EMO i.v. will be administered twice, at baseline and post dosing with scopolamine.
  arm group label: Scopolamine high dose
  arm group label: Scopolamine low dose
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: Accepts Healthy Volunteers
  last name: David Matuskey, MD
  role: Principal Investigator
  affiliation: Yale University
  last name: Mark F Dias, MA
  phone: (203) 737-6128
  email: mark.dias@yale.edu
  facility: 
  country: United States
  responsible party type: Principal Investigator
  investigator affiliation: Yale University
  investigator full name: David Matuskey
  investigator title: Associate Professor
  mesh term: Scopolamine
  mesh term: Butylscopolammonium Bromide
  mesh term: LSN3172176
  sharing ipd: No