<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/NCT03822910</url>
  </required_header>
  <id_info>
    <org_study_id>18-00656</org_study_id>
    <nct_id>NCT03822910</nct_id>
  </id_info>
  <brief_title>Hippocampal Memory Circuits in Delusions</brief_title>
  <official_title>Hippocampal Memory Circuits in Delusions</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>NYU Langone Health</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Institutes of Health (NIH)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>NYU Langone Health</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study will investigate dentate gyrus (DG) and hippocampal CA3 sub field function, using&#xD;
      the pattern separation paradigm, as reflected by the difference in brain activation in&#xD;
      response to same-as-previously- seen (OLD) vs. similar-to-previously-seen (SIM) objects in&#xD;
      first episode psychosis (FEP) subjects before and after anti psychotic treatment and in&#xD;
      matched healthy controls (HC). The current study uses three novel high-resolution task-based&#xD;
      and post-encoding resting fMRI measures to probe hippocampal circuitry in delusions. It will&#xD;
      also study CA1 function, using a sequential associative mismatch paradigm, as reflected by&#xD;
      activation of CA1 in response to mismatching information compared to memory of that stimulus&#xD;
      in FEP subjects before and after antipsychotic treatment and in matched HC. Finally, this&#xD;
      study will evaluate plasticity of hippocampal intrinsic functional connectivity (IFC) in&#xD;
      response to memory consolidation, using an encoding-plasticity paradigm, in FEP subjects&#xD;
      before and after anti psychotic treatment and in matched HC. For each of the three imaging&#xD;
      projects, a total of 50 FEP subjects and 50 matched healthy controls (HC) will be studied;&#xD;
      hence, 300 subjects will be studied over 5 years. Within each paradigm, medication-naive FEP&#xD;
      subjects will be studied at baseline and 8 weeks after starting anti psychotic medication. HC&#xD;
      participants will be studied at baseline and 8 weeks later but will not receive any&#xD;
      treatment.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">July 13, 2019</start_date>
  <completion_date type="Anticipated">April 1, 2024</completion_date>
  <primary_completion_date type="Anticipated">April 1, 2024</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Control</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>The difference in CA1 activation between a mismatch and an intact trial in FEP subjects after 8 weeks of antipsychotic treatment and the correlation of this change with change in delusions as measured by the Psyrats-D total score.</measure>
    <time_frame>8 Weeks</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in hippocampus-to-VTA (hip-VTA) IFC and hip-to-lateral occipital complex (hip-LO) IFC, from pre- to post- encoding during the encoding-plasticity paradigm, between FEP and HC.</measure>
    <time_frame>8 Weeks</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in (a) hip-VTA IFC and (b) hip-LO IFC, from pre- to post- encoding during the encoding-plasticity paradigm</measure>
    <time_frame>8 Weeks</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>correlation of change (a) hip-VTA IFC and (b) hip-LO IFC with change in delusional severity measured by the Psyrats-D total score.</measure>
    <time_frame>8 Weeks</time_frame>
  </primary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Anticipated">300</enrollment>
  <condition>Psychosis</condition>
  <arm_group>
    <arm_group_label>Healthy Controls</arm_group_label>
    <description>Matched Healthy Controls</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Firt Episode Psychosis (FEP)</arm_group_label>
    <description>subjects before and after antipsychotic treatment</description>
  </arm_group>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Pattern Separation Paradigm</intervention_name>
    <description>Will be used to investigate dentate gyrus (DG) and hippocampal CA3 subfield as reflected by the difference in brain activation in response to same as previously seen (OLD) vs similar to previously seen (SIM) objects in first episode (FEP) subjects before and after treatment.</description>
    <arm_group_label>Firt Episode Psychosis (FEP)</arm_group_label>
    <arm_group_label>Healthy Controls</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Sequential Associative Mismatch Paradigm</intervention_name>
    <description>used to reflect activation of CA1 in response to mismatching information compared to memory of the stimulus in FEP subjects before and after antipsychotic treatment and in matched Healthy Control (HC).</description>
    <arm_group_label>Firt Episode Psychosis (FEP)</arm_group_label>
    <arm_group_label>Healthy Controls</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Encoding Plasticity Paradigm</intervention_name>
    <description>Used to evaluate plasticity of hippocampal Intrinsic Functional Connectivity (IFC) in response to memory consolidation in FEP subjects before and after antipsychotic treatment and in matched HC.</description>
    <arm_group_label>Firt Episode Psychosis (FEP)</arm_group_label>
    <arm_group_label>Healthy Controls</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Males and females with First Episode Psychosis&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Males and females 16 to 35 years of age, inclusive, at the time of informed consent&#xD;
&#xD;
          -  Right-handed&#xD;
&#xD;
          -  Must have experienced a first episode of non-affective psychosis over the past five&#xD;
             years&#xD;
&#xD;
          -  Must exhibit a persistence of delusions for at least 4 days per week for at least 4&#xD;
             weeks in the absence of psychotomimetic substance use or other potential organic&#xD;
             etiologies, including epilepsy or significant head trauma.&#xD;
&#xD;
          -  Must score at least a 2 (mild to moderate) on the &quot;Amount of preoccupation with&#xD;
             delusions&quot; and &quot;Conviction&quot; items on the Psychotic Symptom Rating Scale (PSYRATS).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Diagnosis of major mood disorder or other Axis I disorder other than Schizophrenia,&#xD;
             Schizoaffective Disorder or Schizophreniform Disorder.&#xD;
&#xD;
          -  Significant medical or neurological illness by history or physical exam including&#xD;
             seizure disorder, history of loss of consciousness related to head trauma or&#xD;
             developmental disorder including mental retardation.&#xD;
&#xD;
          -  Metal implants, pacemaker, or other metal in the body or medicinal patch.&#xD;
&#xD;
          -  History of claustrophobia.&#xD;
&#xD;
          -  Currently taking any anti psychotic medication (within 4 weeks).&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>16 Years</minimum_age>
    <maximum_age>35 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Donald Goff, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>NYU Langone Health</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Gillian Capichioni</last_name>
    <phone>917-628-0552</phone>
    <email>gillian.capichioni@nyulangone.org</email>
  </overall_contact>
  <location>
    <facility>
      <name>New York Langone Health</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>11375</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Gillian Capichioni</last_name>
      <phone>917-628-0552</phone>
      <email>gillian.capichioni@nyulangone.org</email>
    </contact>
    <investigator>
      <last_name>Donald Goff, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Shanghai Mental Health Center</name>
      <address>
        <city>Shanghai</city>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jujun Wang, MD PhD</last_name>
      <phone>86-21-3428-9888</phone>
      <email>jijunwang27@gmail.com</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Suzhou Guangji Hospital</name>
      <address>
        <city>Suzhou</city>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Junjie Wang, MD</last_name>
      <email>wangjunjie6723@163.com</email>
    </contact>
  </location>
  <location_countries>
    <country>China</country>
    <country>United States</country>
  </location_countries>
  <verification_date>June 2023</verification_date>
  <study_first_submitted>January 23, 2019</study_first_submitted>
  <study_first_submitted_qc>January 29, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 30, 2019</study_first_posted>
  <last_update_submitted>June 1, 2023</last_update_submitted>
  <last_update_submitted_qc>June 1, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">June 5, 2023</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>Delusions</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>To gain access, data requestors will need to sign a data access agreement.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_time_frame>Beginning 3 months and ending 5 years following article publication.</ipd_time_frame>
    <ipd_access_criteria>All of the individual participant data collected during the trial, after deidentification.Researchers who provide a methodologically sound proposal will have access.</ipd_access_criteria>
  </patient_data>
  <!-- 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/NCT03822910
org study id: 18-00656
nct id: NCT03822910
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This study will investigate dentate gyrus (DG) and hippocampal CA3 sub field function, using
      the pattern separation paradigm, as reflected by the difference in brain activation in
      response to same-as-previously- seen (OLD) vs. similar-to-previously-seen (SIM) objects in
      first episode psychosis (FEP) subjects before and after anti psychotic treatment and in
      matched healthy controls (HC). The current study uses three novel high-resolution task-based
      and post-encoding resting fMRI measures to probe hippocampal circuitry in delusions. It will
      also study CA1 function, using a sequential associative mismatch paradigm, as reflected by
      activation of CA1 in response to mismatching information compared to memory of that stimulus
      in FEP subjects before and after antipsychotic treatment and in matched HC. Finally, this
      study will evaluate plasticity of hippocampal intrinsic functional connectivity (IFC) in
      response to memory consolidation, using an encoding-plasticity paradigm, in FEP subjects
      before and after anti psychotic treatment and in matched HC. For each of the three imaging
      projects, a total of 50 FEP subjects and 50 matched healthy controls (HC) will be studied;
      hence, 300 subjects will be studied over 5 years. Within each paradigm, medication-naive FEP
      subjects will be studied at baseline and 8 weeks after starting anti psychotic medication. HC
      participants will be studied at baseline and 8 weeks later but will not receive any
      treatment.
observational model: Case-Control
time perspective: Prospective
measure: The difference in CA1 activation between a mismatch and an intact trial in FEP subjects after 8 weeks of antipsychotic treatment and the correlation of this change with change in delusions as measured by the Psyrats-D total score.
time frame: 8 Weeks
measure: Change in hippocampus-to-VTA (hip-VTA) IFC and hip-to-lateral occipital complex (hip-LO) IFC, from pre- to post- encoding during the encoding-plasticity paradigm, between FEP and HC.
time frame: 8 Weeks
measure: Change in (a) hip-VTA IFC and (b) hip-LO IFC, from pre- to post- encoding during the encoding-plasticity paradigm
time frame: 8 Weeks
measure: correlation of change (a) hip-VTA IFC and (b) hip-LO IFC with change in delusional severity measured by the Psyrats-D total score.
time frame: 8 Weeks
arm group label: Healthy Controls
description: Matched Healthy Controls
arm group label: Firt Episode Psychosis (FEP)
description: subjects before and after antipsychotic treatment
intervention type: Diagnostic Test
intervention name: Pattern Separation Paradigm
description: Will be used to investigate dentate gyrus (DG) and hippocampal CA3 subfield as reflected by the difference in brain activation in response to same as previously seen (OLD) vs similar to previously seen (SIM) objects in first episode (FEP) subjects before and after treatment.
arm group label: Firt Episode Psychosis (FEP)
arm group label: Healthy Controls
intervention type: Diagnostic Test
intervention name: Sequential Associative Mismatch Paradigm
description: used to reflect activation of CA1 in response to mismatching information compared to memory of the stimulus in FEP subjects before and after antipsychotic treatment and in matched Healthy Control (HC).
arm group label: Firt Episode Psychosis (FEP)
arm group label: Healthy Controls
intervention type: Diagnostic Test
intervention name: Encoding Plasticity Paradigm
description: Used to evaluate plasticity of hippocampal Intrinsic Functional Connectivity (IFC) in response to memory consolidation in FEP subjects before and after antipsychotic treatment and in matched HC.
arm group label: Firt Episode Psychosis (FEP)
arm group label: Healthy Controls
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 16 Years
maximum age: 35 Years
healthy volunteers: No
last name: Donald Goff, MD
role: Principal Investigator
affiliation: NYU Langone Health
last name: Gillian Capichioni
phone: 917-628-0552
email: gillian.capichioni@nyulangone.org
facility: 
status: Not yet recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
country: China
country: United States
responsible party type: Sponsor
mesh term: Delusions
sharing ipd: Yes
ipd description: To gain access, data requestors will need to sign a data access agreement.
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Informed Consent Form (ICF)
ipd time frame: Beginning 3 months and ending 5 years following article publication.
ipd access criteria: All of the individual participant data collected during the trial, after deidentification.Researchers who provide a methodologically sound proposal will have access.