<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/NCT03030391</url>
  </required_header>
  <id_info>
    <org_study_id>170041</org_study_id>
    <secondary_id>17-M-0041</secondary_id>
    <nct_id>NCT03030391</nct_id>
  </id_info>
  <brief_title>Novel Positron Emission Tomography (PET) Radiotracer to Image Phosphodiesterase-4B (PDE4B)</brief_title>
  <official_title>Evaluation of a Novel Positron Emission Tomography (PET) Radiotracer to Image Phosphodiesterase-4B (PDE4B)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National Institute of Mental Health (NIMH)</agency>
      <agency_class>NIH</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>National Institutes of Health Clinical Center (CC)</source>
  <brief_summary>
    <textblock>
      Background:&#xD;
&#xD;
      The new drug 18F-PF-06445974 has a little radioactivity. This can be seen by a positron&#xD;
      emission tomography (PET) scan. The drug helps researchers see a protein, PDE4B, in the&#xD;
      brain. Looking at PDE4B in the living brain might show how it is involved in psychiatric and&#xD;
      neurological disorders. One part of the study will look at how the study drug is distributed&#xD;
      in the brain. Another part will study how brain measures vary.&#xD;
&#xD;
      Objectives:&#xD;
&#xD;
      To measure the protein PDE4B in the brain. To test how a new radioactive chemical,&#xD;
      18F-PF-06445974, is distributed in the body.&#xD;
&#xD;
      Eligibility:&#xD;
&#xD;
      Healthy adults ages 18 and older&#xD;
&#xD;
      Design:&#xD;
&#xD;
      Participants will have 1-3 visits over a year. Each will be 2-5 hours.&#xD;
&#xD;
      Women will have a pregnancy test each time.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Objective:&#xD;
&#xD;
      Phosphodiesterase type 4 (PDE4) terminates signal transduction of guanine nucleotidebinding&#xD;
      proteins (G-protein)-coupled receptors by metabolizing the second messenger 3 &lt;=,5 &lt;=- cyclic&#xD;
      adenosine monophosphate (cAMP). PDE4 is selective to cAMP over cyclic guanosine&#xD;
      monophosphate. PDE4 has four isozymes A, B, C, and D and basic studies indicate that type B&#xD;
      (PDE4B) plays a key role in cognitive function and neuroinflammation. Thus, PDE4B inhibitors&#xD;
      would be expected to improve cognitive function and have anti-inflammatory effects. Pfizer&#xD;
      has developed a new PET ligand, 18F-PF-06445974, to selectively image PDE4B; the ligand has&#xD;
      shown promising results in non-human primates.&#xD;
&#xD;
      This protocol covers four phases:&#xD;
&#xD;
        1. Phase 1: whole body imaging of one subject with a low injection activity of 2 mCi to&#xD;
           confirm that no organ has prominently high uptake of 18F-PF-06445974;&#xD;
&#xD;
        2. Phase 2: kinetic brain imaging with up to 5 mCi injection to quantify PDE4B in brain&#xD;
           relative to concurrent measurement of the parent radioligand in arterial plasma;&#xD;
&#xD;
        3. Phase 3: if 18F-PF-06445974 is successful in Phase 2 in the first couple of subjects, we&#xD;
           will estimate the radiation-absorbed doses by performing whole body imaging with 5 mCi&#xD;
           injection;&#xD;
&#xD;
        4. Phase 4: test-retest analysis of brain binding relative to concurrent measurement of the&#xD;
           parent radioligand in arterial plasma (5 mCi per scan).&#xD;
&#xD;
      Study Population:&#xD;
&#xD;
      Healthy adult female and male volunteers (n=22, ages 18 or older) will undergo brain imaging.&#xD;
      An additional eight healthy volunteers will undergo whole body dosimetry analysis, for a&#xD;
      total of 30 healthy volunteers.&#xD;
&#xD;
      Design:&#xD;
&#xD;
      For quantification of 18F-PF-06445974, 22 healthy controls will undergo brain PET imaging&#xD;
      using 18F-PF-06445974 and an arterial line. Some of them will have a test-retest scan. Eight&#xD;
      additional subjects will have a whole body PET scan for dosimetry. For dosimetry, no arterial&#xD;
      line will be used.&#xD;
&#xD;
      Outcome Measures:&#xD;
&#xD;
      To assess quantitation of PDE4B with 18F-PF-06445974, we will primarily use two outcome&#xD;
      measures, namely the identifiability and time stability of distribution volume (VT)&#xD;
      calculated with compartmental modeling. In the test-retest study, we will calculate the&#xD;
      retest&#xD;
&#xD;
      variability. We will assess whole-body biodistribution and dosimetry of 18F-PF-06445974 by&#xD;
      calculating doses to organs and effective dose to the body.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <start_date>January 10, 2017</start_date>
  <completion_date type="Actual">March 16, 2018</completion_date>
  <primary_completion_date type="Actual">March 16, 2018</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Diagnostic</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Quantification of 18F-PF-06445974 binding in brain</measure>
    <time_frame>2 hours</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Biodistribution of 18F-PF-06445974 in the body.</measure>
    <time_frame>2 hours</time_frame>
  </secondary_outcome>
  <enrollment type="Actual">5</enrollment>
  <condition>Healthy</condition>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>PET</intervention_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>MRI</intervention_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        -  INCLUSION CRITERIA:&#xD;
&#xD;
          -  Age 18 or older.&#xD;
&#xD;
          -  Able to give written informed consent.&#xD;
&#xD;
          -  Medically and psychiatrically healthy.&#xD;
&#xD;
          -  Enrolled in 01-M-0254 The Evaluation of Participants with Mood and Anxiety Disorders&#xD;
             and Healthy Volunteers (PI: Dr. Carlos Zarate).&#xD;
&#xD;
        EXCLUSION CRITERIA:&#xD;
&#xD;
          -  Any current Axis I diagnosis.&#xD;
&#xD;
          -  Clinically significant laboratory abnormalities&#xD;
&#xD;
          -  Positive HIV test.&#xD;
&#xD;
          -  Unable to have an MRI scan.&#xD;
&#xD;
          -  History of neurologic illness or injury with the potential to affect study data&#xD;
             interpretation.&#xD;
&#xD;
          -  Recent exposure to radiation related to research (i.e. PET from other research) that,&#xD;
             when combined with this study, would be above the allowable limits.&#xD;
&#xD;
          -  Inability to lie flat on camera bed for at least two hours.&#xD;
&#xD;
          -  Pregnancy or breastfeeding.&#xD;
&#xD;
          -  Current substance use disorder based on DSM-5.&#xD;
&#xD;
          -  Current use of psychiatric medications.&#xD;
&#xD;
          -  NIMH employees/staff and their immediate family members will be excluded from the&#xD;
             study per NIMH policy.&#xD;
&#xD;
        Exclusion criteria for the dosimetry subjects are the same as reported above, with the&#xD;
        exception of MRI contraindications, because an MRI will not be performed in these subjects.&#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>Masahiro Fujita, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>National Institute of Mental Health (NIMH)</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>National Institutes of Health Clinical Center</name>
      <address>
        <city>Bethesda</city>
        <state>Maryland</state>
        <zip>20892</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>March 16, 2018</verification_date>
  <study_first_submitted>January 24, 2017</study_first_submitted>
  <study_first_submitted_qc>January 24, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 25, 2017</study_first_posted>
  <last_update_submitted>December 14, 2019</last_update_submitted>
  <last_update_submitted_qc>December 14, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">December 17, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Camp</keyword>
  <keyword>Radiation Absorbed Dose</keyword>
  <keyword>Compartmental Analysis</keyword>
  <!-- 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/NCT03030391
org study id: 170041
secondary id: 17-M-0041
nct id: NCT03030391
lead sponsor: 
Background:

      The new drug 18F-PF-06445974 has a little radioactivity. This can be seen by a positron
      emission tomography (PET) scan. The drug helps researchers see a protein, PDE4B, in the
      brain. Looking at PDE4B in the living brain might show how it is involved in psychiatric and
      neurological disorders. One part of the study will look at how the study drug is distributed
      in the brain. Another part will study how brain measures vary.

      Objectives:

      To measure the protein PDE4B in the brain. To test how a new radioactive chemical,
      18F-PF-06445974, is distributed in the body.

      Eligibility:

      Healthy adults ages 18 and older

      Design:

      Participants will have 1-3 visits over a year. Each will be 2-5 hours.

      Women will have a pregnancy test each time.
Objective:

      Phosphodiesterase type 4 (PDE4) terminates signal transduction of guanine nucleotidebinding
      proteins (G-protein)-coupled receptors by metabolizing the second messenger 3 <=,5 <=- cyclic
      adenosine monophosphate (cAMP). PDE4 is selective to cAMP over cyclic guanosine
      monophosphate. PDE4 has four isozymes A, B, C, and D and basic studies indicate that type B
      (PDE4B) plays a key role in cognitive function and neuroinflammation. Thus, PDE4B inhibitors
      would be expected to improve cognitive function and have anti-inflammatory effects. Pfizer
      has developed a new PET ligand, 18F-PF-06445974, to selectively image PDE4B; the ligand has
      shown promising results in non-human primates.

      This protocol covers four phases:

        1. Phase 1: whole body imaging of one subject with a low injection activity of 2 mCi to
           confirm that no organ has prominently high uptake of 18F-PF-06445974;

        2. Phase 2: kinetic brain imaging with up to 5 mCi injection to quantify PDE4B in brain
           relative to concurrent measurement of the parent radioligand in arterial plasma;

        3. Phase 3: if 18F-PF-06445974 is successful in Phase 2 in the first couple of subjects, we
           will estimate the radiation-absorbed doses by performing whole body imaging with 5 mCi
           injection;

        4. Phase 4: test-retest analysis of brain binding relative to concurrent measurement of the
           parent radioligand in arterial plasma (5 mCi per scan).

      Study Population:

      Healthy adult female and male volunteers (n=22, ages 18 or older) will undergo brain imaging.
      An additional eight healthy volunteers will undergo whole body dosimetry analysis, for a
      total of 30 healthy volunteers.

      Design:

      For quantification of 18F-PF-06445974, 22 healthy controls will undergo brain PET imaging
      using 18F-PF-06445974 and an arterial line. Some of them will have a test-retest scan. Eight
      additional subjects will have a whole body PET scan for dosimetry. For dosimetry, no arterial
      line will be used.

      Outcome Measures:

      To assess quantitation of PDE4B with 18F-PF-06445974, we will primarily use two outcome
      measures, namely the identifiability and time stability of distribution volume (VT)
      calculated with compartmental modeling. In the test-retest study, we will calculate the
      retest

      variability. We will assess whole-body biodistribution and dosimetry of 18F-PF-06445974 by
      calculating doses to organs and effective dose to the body.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Diagnostic
masking: None (Open Label)
measure: Quantification of 18F-PF-06445974 binding in brain
time frame: 2 hours
measure: Biodistribution of 18F-PF-06445974 in the body.
time frame: 2 hours
intervention type: Other
intervention name: PET
intervention type: Other
intervention name: MRI
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Masahiro Fujita, M.D.
role: Principal Investigator
affiliation: National Institute of Mental Health (NIMH)
facility: 
country: United States
responsible party type: Sponsor