<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/NCT02230592</url>
  </required_header>
  <id_info>
    <org_study_id>140016</org_study_id>
    <secondary_id>14-M-0016</secondary_id>
    <nct_id>NCT02230592</nct_id>
  </id_info>
  <brief_title>PET Imaging of Brain mGluR1 Receptors Using [18F]FIMX</brief_title>
  <official_title>PET Imaging of Brain mGluR1 Receptors Using [18F]FIMX</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>
      Objective:&#xD;
&#xD;
      Metabotropic glutamate receptors (mGluRs) are G-protein coupled receptors that respond to&#xD;
      glutamate by activating proteins inside nerve cells that affect cell metabolism, thereby&#xD;
      fine-tuning the signals sent between cells to maintain balance in neuronal activity. mGluR&#xD;
      subtype 1 (mGluR1s) are located in several brain regions, including the cerebellum,&#xD;
      hippocampus, olfactory bulb, and basal ganglia. mGluR1 activation stimulates phospholipase C,&#xD;
      resulting in phosphoinositide hydrolysis and increased intracellular calcium levels.&#xD;
      Successful development of a positron emission tomography (PET) ligand to image mGlurR1 would&#xD;
      impact clinical management of brain disorders characterized by disruptions in glutamatergic&#xD;
      transmission, including anxiety and stress disorders, drug addiction, epilepsy, Huntington s&#xD;
      disease, and Parkinson s disease. However, detailed study of mGluR1s has heretofore been&#xD;
      hindered by the lack of high affinity and selective ligands for this receptor subtype.&#xD;
&#xD;
      The present protocol will evaluate the ability of a new PET ligand, [18F]FIMX, to image and&#xD;
      quantify mGluR1 in the brain of healthy human volunteers. This protocol covers four phases:&#xD;
&#xD;
        1. Phase 0: screening whole-body scan;&#xD;
&#xD;
        2. Phase 1: kinetic brain imaging to quantify mGluR1 in brain relative to concurrent&#xD;
           measurement of the parent radioligand in arterial plasma;&#xD;
&#xD;
        3. Phase 2: if the tracer is successful in Phase 1, we will estimate radiation-absorbed&#xD;
           doses of [18F]FIMX by performing whole body imaging;&#xD;
&#xD;
        4. Phase 3: test-retest analysis of brain binding relative to concurrent measurement of the&#xD;
           parent radioligand in arterial plasma.&#xD;
&#xD;
      Study Population:&#xD;
&#xD;
      Healthy adult female and male volunteers (n=22, ages 18 to 55) will undergo brain or&#xD;
      whole-body imaging..&#xD;
&#xD;
      Design:&#xD;
&#xD;
      This study will begin with a screening whole-body scan to confirm that the radioactivity has&#xD;
      fairly broad distribution in several organs. For absolute quantification of mGluR1, 22&#xD;
      healthy controls will have brain PET imaging using [18F]FIMX and an arterial line. Up to 12&#xD;
      of them will have a test-retest scan. Eight additional subjects will have a whole body PET&#xD;
      scan for dosimetry, which does not require an arterial line.&#xD;
&#xD;
      &lt;TAB&gt;&#xD;
&#xD;
      Outcome Measures&#xD;
&#xD;
      To assess absolute quantitation of mGluR1 with [18F]FIMX, we will primarily use two outcome&#xD;
      measures: the identifiability and time stability of distribution volume calculated with&#xD;
      compartmental modeling. In test-retest study, we will calculate the retest variability. To&#xD;
      assess whole-body biodistribution and dosimetry of [18F]FIMX we will use the organ&#xD;
      time-activity curves....&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Objective:&#xD;
&#xD;
      Metabotropic glutamate receptors (mGluRs) are G-protein coupled receptors that respond to&#xD;
      glutamate by activating proteins inside nerve cells that affect cell metabolism, thereby&#xD;
      fine-tuning the signals sent between cells to maintain balance in neuronal activity. mGluR&#xD;
      subtype 1 (mGluR1s) are located in several brain regions, including the cerebellum,&#xD;
      hippocampus, olfactory bulb, and basal ganglia. mGluR1 activation stimulates phospholipase C,&#xD;
      resulting in phosphoinositide hydrolysis and increased intracellular calcium levels.&#xD;
      Successful development of a positron emission tomography (PET) ligand to image mGlurR1 would&#xD;
      impact clinical management of brain disorders characterized by disruptions in glutamatergic&#xD;
      transmission, including anxiety and stress disorders, drug addiction, epilepsy, Huntington s&#xD;
      disease, and Parkinson s disease. However, detailed study of mGluR1s has heretofore been&#xD;
      hindered by the lack of high affinity and selective ligands for this receptor subtype.&#xD;
&#xD;
      The present protocol will evaluate the ability of a new PET ligand, [18F]FIMX, to image and&#xD;
      quantify mGluR1 in the brain of healthy human volunteers. This protocol covers four phases:&#xD;
&#xD;
        1. Phase 0: screening whole-body scan;&#xD;
&#xD;
        2. Phase 1: kinetic brain imaging to quantify mGluR1 in brain relative to concurrent&#xD;
           measurement of the parent radioligand in arterial plasma;&#xD;
&#xD;
        3. Phase 2: if the tracer is successful in Phase 1, we will estimate radiation-absorbed&#xD;
           doses of [18F]FIMX by performing whole body imaging;&#xD;
&#xD;
        4. Phase 3: test-retest analysis of brain binding relative to concurrent measurement of the&#xD;
           parent radioligand in arterial plasma.&#xD;
&#xD;
      Study Population:&#xD;
&#xD;
      Healthy adult female and male volunteers (n=22, ages 18 to 55) will undergo brain or&#xD;
      whole-body imaging.&#xD;
&#xD;
      Design:&#xD;
&#xD;
      This study will begin with a screening whole-body scan to confirm that the radioactivity has&#xD;
      fairly broad distribution in several organs. For absolute quantification of mGluR1, 22&#xD;
      healthy controls will have brain PET imaging using [18F]FIMX and an arterial line. Up to 12&#xD;
      of them will have a test-retest scan. Eight additional subjects will have a whole body PET&#xD;
      scan for dosimetry, which does not require an arterial line.&#xD;
&#xD;
      &lt;TAB&gt;&#xD;
&#xD;
      Outcome Measures&#xD;
&#xD;
      To assess absolute quantitation of mGluR1 with [18F]FIMX, we will primarily use two outcome&#xD;
      measures: the identifiability and time stability of distribution volume calculated with&#xD;
      compartmental modeling. In test-retest study, we will calculate the retest variability. To&#xD;
      assess whole-body biodistribution and dosimetry of [18F]FIMX we will use the organ&#xD;
      time-activity curves.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>November 8, 2013</start_date>
  <completion_date type="Actual">June 16, 2016</completion_date>
  <primary_completion_date type="Actual">June 16, 2016</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Ability to measure mGluR1 in brain</measure>
    <time_frame>3 years</time_frame>
  </primary_outcome>
  <enrollment type="Actual">19</enrollment>
  <condition>Anxiety Disorder</condition>
  <condition>Major Depressive Disorder</condition>
  <eligibility>
    <criteria>
      <textblock>
        -  INCLUSION CRITERIA:&#xD;
&#xD;
          -  Age 18 to 55.&#xD;
&#xD;
          -  Able to give written informed consent.&#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 (i.e. PET from other research) that, when combined with&#xD;
             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 breast feeding.&#xD;
&#xD;
          -  Able to get pregnant but does not use birth control.&#xD;
&#xD;
          -  History of drug or alcohol abuse within 6 months or a history of alcohol or drug&#xD;
             dependence (excepting nicotine) within 3 years&#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>55 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Robert B Innis, 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, 9000 Rockville Pike</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>
  <reference>
    <citation>Anwyl R. Metabotropic glutamate receptors: electrophysiological properties and role in plasticity. Brain Res Brain Res Rev. 1999 Jan;29(1):83-120. doi: 10.1016/s0165-0173(98)00050-2.</citation>
    <PMID>9974152</PMID>
  </reference>
  <reference>
    <citation>Battaglia G, Bruno V, Pisani A, Centonze D, Catania MV, Calabresi P, Nicoletti F. Selective blockade of type-1 metabotropic glutamate receptors induces neuroprotection by enhancing gabaergic transmission. Mol Cell Neurosci. 2001 Jun;17(6):1071-83. doi: 10.1006/mcne.2001.0992.</citation>
    <PMID>11414795</PMID>
  </reference>
  <reference>
    <citation>Bordi F, Ugolini A. Group I metabotropic glutamate receptors: implications for brain diseases. Prog Neurobiol. 1999 Sep;59(1):55-79. doi: 10.1016/s0301-0082(98)00095-1.</citation>
    <PMID>10416961</PMID>
  </reference>
  <verification_date>July 18, 2016</verification_date>
  <study_first_submitted>August 28, 2014</study_first_submitted>
  <study_first_submitted_qc>August 29, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 3, 2014</study_first_posted>
  <last_update_submitted>July 3, 2018</last_update_submitted>
  <last_update_submitted_qc>July 3, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">July 5, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>PET</keyword>
  <keyword>Metabolic Glutamate Receptors</keyword>
  <keyword>Brain Imaging</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Depressive Disorder</mesh_term>
    <mesh_term>Depressive Disorder, Major</mesh_term>
    <mesh_term>Anxiety Disorders</mesh_term>
  </condition_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/NCT02230592
org study id: 140016
secondary id: 14-M-0016
nct id: NCT02230592
lead sponsor: 
Objective:

      Metabotropic glutamate receptors (mGluRs) are G-protein coupled receptors that respond to
      glutamate by activating proteins inside nerve cells that affect cell metabolism, thereby
      fine-tuning the signals sent between cells to maintain balance in neuronal activity. mGluR
      subtype 1 (mGluR1s) are located in several brain regions, including the cerebellum,
      hippocampus, olfactory bulb, and basal ganglia. mGluR1 activation stimulates phospholipase C,
      resulting in phosphoinositide hydrolysis and increased intracellular calcium levels.
      Successful development of a positron emission tomography (PET) ligand to image mGlurR1 would
      impact clinical management of brain disorders characterized by disruptions in glutamatergic
      transmission, including anxiety and stress disorders, drug addiction, epilepsy, Huntington s
      disease, and Parkinson s disease. However, detailed study of mGluR1s has heretofore been
      hindered by the lack of high affinity and selective ligands for this receptor subtype.

      The present protocol will evaluate the ability of a new PET ligand, [18F]FIMX, to image and
      quantify mGluR1 in the brain of healthy human volunteers. This protocol covers four phases:

        1. Phase 0: screening whole-body scan;

        2. Phase 1: kinetic brain imaging to quantify mGluR1 in brain relative to concurrent
           measurement of the parent radioligand in arterial plasma;

        3. Phase 2: if the tracer is successful in Phase 1, we will estimate radiation-absorbed
           doses of [18F]FIMX by performing whole body imaging;

        4. Phase 3: test-retest analysis of brain binding relative to concurrent measurement of the
           parent radioligand in arterial plasma.

      Study Population:

      Healthy adult female and male volunteers (n=22, ages 18 to 55) will undergo brain or
      whole-body imaging..

      Design:

      This study will begin with a screening whole-body scan to confirm that the radioactivity has
      fairly broad distribution in several organs. For absolute quantification of mGluR1, 22
      healthy controls will have brain PET imaging using [18F]FIMX and an arterial line. Up to 12
      of them will have a test-retest scan. Eight additional subjects will have a whole body PET
      scan for dosimetry, which does not require an arterial line.

      <TAB>

      Outcome Measures

      To assess absolute quantitation of mGluR1 with [18F]FIMX, we will primarily use two outcome
      measures: the identifiability and time stability of distribution volume calculated with
      compartmental modeling. In test-retest study, we will calculate the retest variability. To
      assess whole-body biodistribution and dosimetry of [18F]FIMX we will use the organ
      time-activity curves....
Objective:

      Metabotropic glutamate receptors (mGluRs) are G-protein coupled receptors that respond to
      glutamate by activating proteins inside nerve cells that affect cell metabolism, thereby
      fine-tuning the signals sent between cells to maintain balance in neuronal activity. mGluR
      subtype 1 (mGluR1s) are located in several brain regions, including the cerebellum,
      hippocampus, olfactory bulb, and basal ganglia. mGluR1 activation stimulates phospholipase C,
      resulting in phosphoinositide hydrolysis and increased intracellular calcium levels.
      Successful development of a positron emission tomography (PET) ligand to image mGlurR1 would
      impact clinical management of brain disorders characterized by disruptions in glutamatergic
      transmission, including anxiety and stress disorders, drug addiction, epilepsy, Huntington s
      disease, and Parkinson s disease. However, detailed study of mGluR1s has heretofore been
      hindered by the lack of high affinity and selective ligands for this receptor subtype.

      The present protocol will evaluate the ability of a new PET ligand, [18F]FIMX, to image and
      quantify mGluR1 in the brain of healthy human volunteers. This protocol covers four phases:

        1. Phase 0: screening whole-body scan;

        2. Phase 1: kinetic brain imaging to quantify mGluR1 in brain relative to concurrent
           measurement of the parent radioligand in arterial plasma;

        3. Phase 2: if the tracer is successful in Phase 1, we will estimate radiation-absorbed
           doses of [18F]FIMX by performing whole body imaging;

        4. Phase 3: test-retest analysis of brain binding relative to concurrent measurement of the
           parent radioligand in arterial plasma.

      Study Population:

      Healthy adult female and male volunteers (n=22, ages 18 to 55) will undergo brain or
      whole-body imaging.

      Design:

      This study will begin with a screening whole-body scan to confirm that the radioactivity has
      fairly broad distribution in several organs. For absolute quantification of mGluR1, 22
      healthy controls will have brain PET imaging using [18F]FIMX and an arterial line. Up to 12
      of them will have a test-retest scan. Eight additional subjects will have a whole body PET
      scan for dosimetry, which does not require an arterial line.

      <TAB>

      Outcome Measures

      To assess absolute quantitation of mGluR1 with [18F]FIMX, we will primarily use two outcome
      measures: the identifiability and time stability of distribution volume calculated with
      compartmental modeling. In test-retest study, we will calculate the retest variability. To
      assess whole-body biodistribution and dosimetry of [18F]FIMX we will use the organ
      time-activity curves.
time perspective: Prospective
measure: Ability to measure mGluR1 in brain
time frame: 3 years
criteria: 
gender: All
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Robert B Innis, M.D.
role: Principal Investigator
affiliation: National Institute of Mental Health (NIMH)
facility: 
country: United States
citation: Anwyl R. Metabotropic glutamate receptors: electrophysiological properties and role in plasticity. Brain Res Brain Res Rev. 1999 Jan;29(1):83-120. doi: 10.1016/s0165-0173(98)00050-2.
PMID: 9974152
citation: Battaglia G, Bruno V, Pisani A, Centonze D, Catania MV, Calabresi P, Nicoletti F. Selective blockade of type-1 metabotropic glutamate receptors induces neuroprotection by enhancing gabaergic transmission. Mol Cell Neurosci. 2001 Jun;17(6):1071-83. doi: 10.1006/mcne.2001.0992.
PMID: 11414795
citation: Bordi F, Ugolini A. Group I metabotropic glutamate receptors: implications for brain diseases. Prog Neurobiol. 1999 Sep;59(1):55-79. doi: 10.1016/s0301-0082(98)00095-1.
PMID: 10416961
responsible party type: Sponsor
mesh term: Depressive Disorder
mesh term: Depressive Disorder, Major
mesh term: Anxiety Disorders