<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/NCT02983058</url>
  </required_header>
  <id_info>
    <org_study_id>#7107</org_study_id>
    <nct_id>NCT02983058</nct_id>
  </id_info>
  <brief_title>PET Imaging Study of Amish and Mennonite Patients With CNTNAP2 Mutations</brief_title>
  <official_title>PET Imaging Study of Amish and Mennonite Patients With CNTNAP2 Mutations</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Jeffrey A. Lieberman, MD</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>New York State Psychiatric Institute</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The primary goal of the present study is to evaluate the utility of mGluR5 binding as&#xD;
      measured by PET as biomarker of the CNTNAP2 mutation and related mTOR kinase pathway&#xD;
      dysregulation.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The investigators will focus on mGluR5 PET binding as a surrogate measure for level of&#xD;
      activity of the mTOR kinase pathway. This study is being conducted by the New York State&#xD;
      Psychiatric Institute (NYSPI) and will take place at Columbia University Medical Center&#xD;
      (CUMC) in New York City and at a research office in Strasburg, PA. Subjects (n=20) with the&#xD;
      CNTNAP2 mutation with schizophrenia or a related condition will be recruited from the Amish&#xD;
      and Mennonite communities and brought to CUMC for detailed investigation. Affected&#xD;
      individuals will be compared to Amish and Mennonite control subjects drawn from the same&#xD;
      families but not harboring CNTNAP2 mutations (n=20). The primary measure will consist of&#xD;
      mGluR PET binding in DLPFC. In addition, secondary analyses will assess binding in other&#xD;
      brain regions such as hippocampus and visual cortex. Exploratory measures, as well as&#xD;
      relationships between PET mGluR5 binding and clinical symptomatology, will be assessed.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    To obtain funding for a larger study&#xD;
  </why_stopped>
  <start_date>November 2016</start_date>
  <completion_date type="Actual">July 2017</completion_date>
  <primary_completion_date type="Actual">July 2017</primary_completion_date>
  <phase>N/A</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>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Level of mGluR5 PET Binding in Dorsolateral Prefrontal Cortex (DLPFC) in CNTNAP2 Mutation Carriers vs. Comparison Subjects</measure>
    <time_frame>90 minutes and the comparison will be binding in the specific regions listed (e.g., DLPFC) controlled by binding in the cerebellum/input function</time_frame>
    <description>Outcome measure is total distribution volume (VT) where distribution volume of the non displaceable compartment (VND) plus binding potential (BPP) with respect to the arterial plasma concentration of tracer. VT=VND + BPP</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Level of mGluR5 PET Binding in Hippocampus</measure>
    <time_frame>90 minutes and the comparison will be binding in the specific regions listed controlled by binding in the cerebellum/input function</time_frame>
    <description>Evaluate PET mGluR5 binding in other regions of potential relevance, including hippocampus in order to determine ideal regions of interest for future intervention studies by using VT=VND + BPP. VND is assumed to be equal across brain regions and therefore VT will vary across brain regions with mGluR5 concentration.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Level of mGluR5 PET Binding in Primary Visual Cortex (Occipital Pole)</measure>
    <time_frame>90 minutes and the comparison will be binding in the specific regions listed controlled by binding in the cerebellum/input function</time_frame>
    <description>Evaluate PET mGluR5 binding in other regions of potential relevance, including primary visual cortex in order to determine ideal regions of interest for future intervention studies as measured by total distribution volume (VT).</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">12</enrollment>
  <condition>Schizophrenia</condition>
  <arm_group>
    <arm_group_label>PET/SPECT and MRI scans</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>PET/SPECT scan will be used to evaluate the utility of mGluR5 binding as a biomarker of the CNTNAP2 mutation and related mTOR kinase pathway dysregulation. 30 minutes structural MRI will be obtained to permit co-registration of PET images.</description>
  </arm_group>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>PET/SPECT Scan</intervention_name>
    <description>PET scan will be performed on a mCT scanner</description>
    <arm_group_label>PET/SPECT and MRI scans</arm_group_label>
    <other_name>PET</other_name>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>MRI Scan</intervention_name>
    <description>Structural MRI will be obtained to permit co-registration of PET images</description>
    <arm_group_label>PET/SPECT and MRI scans</arm_group_label>
    <other_name>MRI</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Patients:&#xD;
&#xD;
          -  Meets DSM-5 diagnostic criteria for psychotic disorder, including schizophrenia,&#xD;
             schizoaffective disorder or psychotic disorder not elsewhere classified&#xD;
&#xD;
          -  Genetic confirmation that patient carries CNTNAP2 mutation&#xD;
&#xD;
          -  Of Amish and/or Mennonite descent&#xD;
&#xD;
          -  Has a relative willing to be part of the study and this relative will travel with the&#xD;
             participant to CUMC in NYC and back to Lancaster, PA&#xD;
&#xD;
          -  Stable enough to travel and participate in the study&#xD;
&#xD;
        Control subjects:&#xD;
&#xD;
          -  Genetic confirmation that subject does not carry CNTNAP2 mutation&#xD;
&#xD;
          -  First-degree or second-degree relative of subject of Amish/Mennonite descent with&#xD;
             CNTNAP2 mutation&#xD;
&#xD;
        Exclusion Criteria (for patients and controls):&#xD;
&#xD;
          -  Positive urine toxicology for drugs of abuse&#xD;
&#xD;
          -  Positive history of severe neurological illness or history of brain trauma&#xD;
&#xD;
          -  Positive history of severe medical illness that would increase risk due to PET scan&#xD;
             procedure, or interfere with interpretation of research findings&#xD;
&#xD;
          -  Low hemoglobin (Hb &lt; 11 g/dL in males, Hb &lt; 10 g/dL in females)&#xD;
&#xD;
          -  Lifetime exposure to radiation in the workplace, or lifetime history of participation&#xD;
             in nuclear medicine procedures, including research protocols.&#xD;
&#xD;
          -  Blood donation within 8 weeks of study&#xD;
&#xD;
          -  Presence of clinically significant brain abnormalities&#xD;
&#xD;
          -  Female subjects of child-bearing age who are not surgically sterilized and between&#xD;
             menarche and 1 year postmenopausal must test negative for pregnancy at the time of&#xD;
             enrollment and prior to the PET scan based on a serum pregnancy test. Women who are&#xD;
             breast-feeding are also excluded.&#xD;
&#xD;
          -  Metal implants, pacemakers, other metal (e.g., shrapnel or surgical prostheses) or&#xD;
             paramagnetic objects contained within the body which may present a risk to the subject&#xD;
             or interfere with the MR scan&#xD;
&#xD;
          -  Medicinal patch, unless removed prior to the MR scan&#xD;
&#xD;
          -  Patients: current treatment with clozapine and/or medications other than&#xD;
             antipsychotics PRN anxiolytics&#xD;
&#xD;
          -  Use of the medications that would interfere with mGluR5 binding, including&#xD;
             lamotrigine, gabapentin, topiramate, phenobarbital, pregabalin, zonisamide,&#xD;
             N-acetylcysteine, D-cycloserine&#xD;
&#xD;
          -  Control subjects: lifetime history of antipsychotic or antidepressant use&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>59 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Sander Markx, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>New York State Psychiatric Institute</affiliation>
  </overall_official>
  <verification_date>May 2020</verification_date>
  <study_first_submitted>August 25, 2016</study_first_submitted>
  <study_first_submitted_qc>December 1, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 6, 2016</study_first_posted>
  <results_first_submitted>May 22, 2019</results_first_submitted>
  <results_first_submitted_qc>May 19, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">June 2, 2020</results_first_posted>
  <last_update_submitted>May 19, 2020</last_update_submitted>
  <last_update_submitted_qc>May 19, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">June 2, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>New York State Psychiatric Institute</investigator_affiliation>
    <investigator_full_name>Jeffrey A. Lieberman, MD</investigator_full_name>
    <investigator_title>Director, New York State Psychiatric Institute</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Schizophrenia</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>November 4, 2016</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/58/NCT02983058/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>May 22, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/58/NCT02983058/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Study subjects were exclusively recruited from the Amish and Mennonite community in Lancaster, Pennsylvania (PA). All subjects with psychotic spectrum disorder were receiving clinical care at the Clinic for Special Children in Strasburg, PA and identified an unaffected 1st or 2nd degree relative (unaffected subject).</recruitment_details>
      <pre_assignment_details>All subjects (affected and unaffected) who met inclusion/exclusion criteria were included in the study.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Subjects With Psychotic Spectrum Disorders</title>
          <description>PET/SPECT scan will be used to evaluate the utility of mGluR5 binding as a biomarker of the CNTNAP2 mutation and related mTOR kinase pathway dysregulation. 30 minutes structural MRI will be obtained to permit co-registration of PET images.&#xD;
PET/SPECT Scan: PET scan will be performed on a mCT scanner&#xD;
MRI Scan: Structural MRI will be obtained to permit co-registration of PET images</description>
        </group>
        <group group_id="P2">
          <title>Unaffected 1st or 2nd Degree Relatives</title>
          <description>PET/SPECT scan will be used to evaluate the utility of mGluR5 binding as a biomarker of the CNTNAP2 mutation and related mTOR kinase pathway dysregulation. 30 minutes structural MRI will be obtained to permit co-registration of PET images.&#xD;
PET/SPECT Scan: PET scan will be performed on a mCT scanner&#xD;
MRI Scan: Structural MRI will be obtained to permit co-registration of PET images</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="7"/>
                <participants group_id="P2" count="5"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="3"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Baseline population numbers include all participants who signed consent and underwent screening procedures</population>
      <group_list>
        <group group_id="B1">
          <title>Subjects With Psychotic Spectrum Disorders</title>
          <description>Subjects who met DSM-5 diagnostic criteria for psychotic disorder and had genetic confirmation of carrying CNTNAP2 mutation</description>
        </group>
        <group group_id="B2">
          <title>Unaffected Relatives</title>
          <description>Unaffected 1st or 2nd degree relatives of subjects who have psychotic spectrum disorder and carries the CNTNAP2 mutation. Unaffected relatives do not carry CNTNAP2 mutation</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="7"/>
            <count group_id="B2" value="5"/>
            <count group_id="B3" value="12"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</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>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="12"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</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_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="2"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="7"/>
                  </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="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="12"/>
                  </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="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </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="7"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Level of mGluR5 PET Binding in Dorsolateral Prefrontal Cortex (DLPFC) in CNTNAP2 Mutation Carriers vs. Comparison Subjects</title>
        <description>Outcome measure is total distribution volume (VT) where distribution volume of the non displaceable compartment (VND) plus binding potential (BPP) with respect to the arterial plasma concentration of tracer. VT=VND + BPP</description>
        <time_frame>90 minutes and the comparison will be binding in the specific regions listed (e.g., DLPFC) controlled by binding in the cerebellum/input function</time_frame>
        <population>N was not reached and data was not analyzed</population>
        <group_list>
          <group group_id="O1">
            <title>Subjects With Psychotic Spectrum Disorders</title>
            <description>PET/SPECT scan will be used to evaluate the utility of mGluR5 binding as a biomarker of the CNTNAP2 mutation and related mTOR kinase pathway dysregulation. 30 minutes structural MRI will be obtained to permit co-registration of PET images.&#xD;
PET/SPECT Scan: PET scan will be performed on a mCT scanner&#xD;
MRI Scan: Structural MRI will be obtained to permit co-registration of PET images</description>
          </group>
          <group group_id="O2">
            <title>Unaffected 1st or 2nd Degree Relatives</title>
            <description>PET/SPECT scan will be used to evaluate the utility of mGluR5 binding as a biomarker of the CNTNAP2 mutation and related mTOR kinase pathway dysregulation. 30 minutes structural MRI will be obtained to permit co-registration of PET images.&#xD;
PET/SPECT Scan: PET scan will be performed on a mCT scanner&#xD;
MRI Scan: Structural MRI will be obtained to permit co-registration of PET images</description>
          </group>
        </group_list>
        <measure>
          <title>Level of mGluR5 PET Binding in Dorsolateral Prefrontal Cortex (DLPFC) in CNTNAP2 Mutation Carriers vs. Comparison Subjects</title>
          <description>Outcome measure is total distribution volume (VT) where distribution volume of the non displaceable compartment (VND) plus binding potential (BPP) with respect to the arterial plasma concentration of tracer. VT=VND + BPP</description>
          <population>N was not reached and data was not analyzed</population>
          <units>mL/cm^3</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="2"/>
                <count group_id="O2" value="2"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="13.58" spread="1.27"/>
                    <measurement group_id="O2" value="11.12" spread="0.24"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Level of mGluR5 PET Binding in Hippocampus</title>
        <description>Evaluate PET mGluR5 binding in other regions of potential relevance, including hippocampus in order to determine ideal regions of interest for future intervention studies by using VT=VND + BPP. VND is assumed to be equal across brain regions and therefore VT will vary across brain regions with mGluR5 concentration.</description>
        <time_frame>90 minutes and the comparison will be binding in the specific regions listed controlled by binding in the cerebellum/input function</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Subjects With Psychotic Spectrum Disorders</title>
            <description>PET/SPECT scan will be used to evaluate the utility of mGluR5 binding as a biomarker of the CNTNAP2 mutation and related mTOR kinase pathway dysregulation. 30 minutes structural MRI will be obtained to permit co-registration of PET images.&#xD;
PET/SPECT Scan: PET scan will be performed on a mCT scanner&#xD;
MRI Scan: Structural MRI will be obtained to permit co-registration of PET images</description>
          </group>
          <group group_id="O2">
            <title>Unaffected 1st or 2nd Degree Relatives</title>
            <description>PET/SPECT scan will be used to evaluate the utility of mGluR5 binding as a biomarker of the CNTNAP2 mutation and related mTOR kinase pathway dysregulation. 30 minutes structural MRI will be obtained to permit co-registration of PET images.&#xD;
PET/SPECT Scan: PET scan will be performed on a mCT scanner&#xD;
MRI Scan: Structural MRI will be obtained to permit co-registration of PET images</description>
          </group>
        </group_list>
        <measure>
          <title>Level of mGluR5 PET Binding in Hippocampus</title>
          <description>Evaluate PET mGluR5 binding in other regions of potential relevance, including hippocampus in order to determine ideal regions of interest for future intervention studies by using VT=VND + BPP. VND is assumed to be equal across brain regions and therefore VT will vary across brain regions with mGluR5 concentration.</description>
          <units>mL/cm^3</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="2"/>
                <count group_id="O2" value="2"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10.61" spread="1.60"/>
                    <measurement group_id="O2" value="11.29" spread="0.53"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Level of mGluR5 PET Binding in Primary Visual Cortex (Occipital Pole)</title>
        <description>Evaluate PET mGluR5 binding in other regions of potential relevance, including primary visual cortex in order to determine ideal regions of interest for future intervention studies as measured by total distribution volume (VT).</description>
        <time_frame>90 minutes and the comparison will be binding in the specific regions listed controlled by binding in the cerebellum/input function</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Subjects With Psychotic Spectrum Disorders</title>
            <description>PET/SPECT scan will be used to evaluate the utility of mGluR5 binding as a biomarker of the CNTNAP2 mutation and related mTOR kinase pathway dysregulation. 30 minutes structural MRI will be obtained to permit co-registration of PET images.&#xD;
PET/SPECT Scan: PET scan will be performed on a mCT scanner&#xD;
MRI Scan: Structural MRI will be obtained to permit co-registration of PET images</description>
          </group>
          <group group_id="O2">
            <title>Unaffected 1st or 2nd Degree Relatives</title>
            <description>PET/SPECT scan will be used to evaluate the utility of mGluR5 binding as a biomarker of the CNTNAP2 mutation and related mTOR kinase pathway dysregulation. 30 minutes structural MRI will be obtained to permit co-registration of PET images.&#xD;
PET/SPECT Scan: PET scan will be performed on a mCT scanner&#xD;
MRI Scan: Structural MRI will be obtained to permit co-registration of PET images</description>
          </group>
        </group_list>
        <measure>
          <title>Level of mGluR5 PET Binding in Primary Visual Cortex (Occipital Pole)</title>
          <description>Evaluate PET mGluR5 binding in other regions of potential relevance, including primary visual cortex in order to determine ideal regions of interest for future intervention studies as measured by total distribution volume (VT).</description>
          <units>mL/cm^3</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="2"/>
                <count group_id="O2" value="2"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10.50" spread="0.87"/>
                    <measurement group_id="O2" value="8.74" spread="1.21"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>From time of consent to 30 days after scans</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Subjects With Psychotic Spectrum Disorders</title>
          <description>PET/SPECT scan will be used to evaluate the utility of mGluR5 binding as a biomarker of the CNTNAP2 mutation and related mTOR kinase pathway dysregulation. 30 minutes structural MRI will be obtained to permit co-registration of PET images.&#xD;
PET/SPECT Scan: PET scan will be performed on a mCT scanner&#xD;
MRI Scan: Structural MRI will be obtained to permit co-registration of PET images</description>
        </group>
        <group group_id="E2">
          <title>Unaffected 1st or 2nd Degree Relatives</title>
          <description>PET/SPECT scan will be used to evaluate the utility of mGluR5 binding as a biomarker of the CNTNAP2 mutation and related mTOR kinase pathway dysregulation. 30 minutes structural MRI will be obtained to permit co-registration of PET images.&#xD;
PET/SPECT Scan: PET scan will be performed on a mCT scanner&#xD;
MRI Scan: Structural MRI will be obtained to permit co-registration of PET images</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="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
              </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>
    <point_of_contact>
      <name_or_title>Marlene Carlson, MPH</name_or_title>
      <organization>New York State Psychiatric Institute</organization>
      <phone>646-774-8436</phone>
      <email>marlene.carlson@nyspi.columbia.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/NCT02983058
org study id: #7107
nct id: NCT02983058
lead sponsor: 
has dmc: No
The primary goal of the present study is to evaluate the utility of mGluR5 binding as
      measured by PET as biomarker of the CNTNAP2 mutation and related mTOR kinase pathway
      dysregulation.
The investigators will focus on mGluR5 PET binding as a surrogate measure for level of
      activity of the mTOR kinase pathway. This study is being conducted by the New York State
      Psychiatric Institute (NYSPI) and will take place at Columbia University Medical Center
      (CUMC) in New York City and at a research office in Strasburg, PA. Subjects (n=20) with the
      CNTNAP2 mutation with schizophrenia or a related condition will be recruited from the Amish
      and Mennonite communities and brought to CUMC for detailed investigation. Affected
      individuals will be compared to Amish and Mennonite control subjects drawn from the same
      families but not harboring CNTNAP2 mutations (n=20). The primary measure will consist of
      mGluR PET binding in DLPFC. In addition, secondary analyses will assess binding in other
      brain regions such as hippocampus and visual cortex. Exploratory measures, as well as
      relationships between PET mGluR5 binding and clinical symptomatology, will be assessed.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: Level of mGluR5 PET Binding in Dorsolateral Prefrontal Cortex (DLPFC) in CNTNAP2 Mutation Carriers vs. Comparison Subjects
time frame: 90 minutes and the comparison will be binding in the specific regions listed (e.g., DLPFC) controlled by binding in the cerebellum/input function
description: Outcome measure is total distribution volume (VT) where distribution volume of the non displaceable compartment (VND) plus binding potential (BPP) with respect to the arterial plasma concentration of tracer. VT=VND + BPP
measure: Level of mGluR5 PET Binding in Hippocampus
time frame: 90 minutes and the comparison will be binding in the specific regions listed controlled by binding in the cerebellum/input function
description: Evaluate PET mGluR5 binding in other regions of potential relevance, including hippocampus in order to determine ideal regions of interest for future intervention studies by using VT=VND + BPP. VND is assumed to be equal across brain regions and therefore VT will vary across brain regions with mGluR5 concentration.
measure: Level of mGluR5 PET Binding in Primary Visual Cortex (Occipital Pole)
time frame: 90 minutes and the comparison will be binding in the specific regions listed controlled by binding in the cerebellum/input function
description: Evaluate PET mGluR5 binding in other regions of potential relevance, including primary visual cortex in order to determine ideal regions of interest for future intervention studies as measured by total distribution volume (VT).
arm group label: PET/SPECT and MRI scans
arm group type: Other
description: PET/SPECT scan will be used to evaluate the utility of mGluR5 binding as a biomarker of the CNTNAP2 mutation and related mTOR kinase pathway dysregulation. 30 minutes structural MRI will be obtained to permit co-registration of PET images.
intervention type: Radiation
intervention name: PET/SPECT Scan
description: PET scan will be performed on a mCT scanner
arm group label: PET/SPECT and MRI scans
other name: PET
intervention type: Device
intervention name: MRI Scan
description: Structural MRI will be obtained to permit co-registration of PET images
arm group label: PET/SPECT and MRI scans
other name: MRI
criteria: 
gender: All
minimum age: 18 Years
maximum age: 59 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Sander Markx, MD
role: Principal Investigator
affiliation: New York State Psychiatric Institute
responsible party type: Sponsor-Investigator
investigator affiliation: New York State Psychiatric Institute
investigator full name: Jeffrey A. Lieberman, MD
investigator title: Director, New York State Psychiatric Institute
mesh term: Schizophrenia
sharing ipd: Undecided
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 