<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/NCT03271814</url>
  </required_header>
  <id_info>
    <org_study_id>HP-00076657</org_study_id>
    <nct_id>NCT03271814</nct_id>
  </id_info>
  <brief_title>Brain Biomarker on Inflammation Response</brief_title>
  <acronym>LPS</acronym>
  <official_title>Brain Biomarker on Inflammation Response</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Maryland, Baltimore</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Maryland, Baltimore</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      In a double-blinded, randomized, parallel controlled design, patients with schizophrenia&#xD;
      spectrum disorder will be exposed to a single dose of lipopolysaccharide (LPS) (LPS-patient).&#xD;
      Clinical symptoms, blood samples, and brain imaging will be assessed at baseline and after&#xD;
      LPS. There will be two comparison groups. Comparison groups include an age- and sex-matched&#xD;
      healthy control group also exposed to the same LPS (LPS-control), and an age- and sex-matched&#xD;
      sample of patients with schizophrenia on placebo (Placebo-patient). As in Phase I studies,&#xD;
      multiple interim analyses are expected so the current design may be modified, which will be&#xD;
      communicated during annual reports (21CFR312.30).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Schizophrenia spectrum disorders are a major public health burden due to functional and&#xD;
      cognitive impairment, psychosis and other symptoms, and high comorbidity. Unfortunately,&#xD;
      current therapies have limited effectiveness in treating some of the symptoms and most of the&#xD;
      cognitive deficits. Alternative biological models of the disease are needed for developing&#xD;
      new and more effective treatment. Neuroinflammation has increasingly been implicated in the&#xD;
      pathophysiology of schizophrenia. Patients with schizophrenia have signs of low-grade,&#xD;
      chronic inflammation, including elevated blood levels of pro-inflammatory cytokines and other&#xD;
      immune markers. Administration of LPS is the standard immune challenge to investigate the&#xD;
      body's immune response in a wide range of disorders. Our goal is to use LPS to investigate&#xD;
      whether schizophrenia patients have abnormal immune response to LPS and whether the&#xD;
      abnormality is associated with specific brain imaging biomarkers.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Not yet recruiting</overall_status>
  <start_date type="Anticipated">January 1, 2025</start_date>
  <completion_date type="Anticipated">December 15, 2025</completion_date>
  <primary_completion_date type="Anticipated">December 15, 2025</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>Triple (Participant, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>IL-6</measure>
    <time_frame>Hourly for 6 hours</time_frame>
    <description>Cytokine IL-6 at baseline and response to LPS challenge (to be reported in pg/ml or IU/ml)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Brain imaging structure and function via MRI</measure>
    <time_frame>3 to 6 hours</time_frame>
    <description>Brain imaging at baseline and response to LPS challenge (to be reported in institutional units)</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Anticipated">75</enrollment>
  <condition>Schizophrenia</condition>
  <arm_group>
    <arm_group_label>LPS-Patient</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Schizophrenia patients who are randomized to receive LPS injection.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>LPS-Healthy</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Healthy controls who are randomized to receive LPS injection.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo-Patient</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Schizophrenia patients who are randomized to receive placebo injection.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>LPS</intervention_name>
    <description>0.6 by/kg LPS single dose iv</description>
    <arm_group_label>LPS-Healthy</arm_group_label>
    <arm_group_label>LPS-Patient</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Sterile Water</description>
    <arm_group_label>Placebo-Patient</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Age 18-55&#xD;
&#xD;
          2. Patients must be on antipsychotic medication and clinically stable, defined as no&#xD;
             hospitalization or major change in antipsychotic medication in the past 4 weeks&#xD;
&#xD;
          3. Patients must pass the ESC with score 10 or above&#xD;
&#xD;
          4. BMI 35 or less -&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. History of major medical illness including, but not limited to, history of heart&#xD;
             attack, stroke, TIA (transient ischemic attack)&#xD;
&#xD;
          2. History of organic brain disorders that may affect neurophysiological measurements,&#xD;
             including seizure disorder, brain tumor, head injury with evidence of significant&#xD;
             cognitive deterioration&#xD;
&#xD;
          3. DSM diagnosis of substance use disorder within 6 months except nicotine and marijuana&#xD;
&#xD;
          4. Prior suicide attempt or frequent suicidal ideations, or current suicidal ideation&#xD;
             assessed by the Columbia Suicide Severity Rating Scale (C-SSRS)&#xD;
&#xD;
          5. Women who have positive urine pregnancy tests; Women who plan to become pregnant, or&#xD;
             are breastfeeding&#xD;
&#xD;
          6. Frequent (more than once) history of syncope (fainting) of unknown reason&#xD;
&#xD;
          7. Unable to undergo MRI scanning due to metallic devices or objects or claustrophobia&#xD;
&#xD;
          8. Presence of co-morbid inflammatory disorders such as rheumatoid arthritis&#xD;
&#xD;
          9. Presence of acute or chronic infection; have received flu or similar vaccine in the&#xD;
             past 4 weeks&#xD;
&#xD;
         10. Current regular use of non-steroidal anti-inflammatory drugs or immune modifying drugs&#xD;
&#xD;
         11. Clinically significant abnormalities on screening laboratory tests&#xD;
&#xD;
         12. Blood pressure &lt;90/60 or &gt; 150/100, or pulse &lt;55 or &gt; 100 beats/minute, or temperature&#xD;
             &gt; 99.5°F&#xD;
&#xD;
         13. 12-Lead ECG demonstrating QTcF &gt;450 msec or a QRS interval &gt;120 msec. If QTcF exceeds&#xD;
             450 msec, or QRS exceeds 120 msec, the ECG should be repeated two more times and the&#xD;
             average of the three QTcF values should be used to determine the subject's eligibility&#xD;
&#xD;
             -&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>15 Years</minimum_age>
    <maximum_age>55 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>L E Hong, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Maryland, Baltimore</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Judy Liu, RN, MSN</last_name>
    <phone>410-402-6832</phone>
    <email>jliu@mprc.umaryland.edu</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Dawn R Detamore</last_name>
    <phone>410-402-6820</phone>
    <email>ddetamor@mprc.umaryland.edu</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>University of Maryland, Baltimore</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21228</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>October 2022</verification_date>
  <study_first_submitted>August 29, 2017</study_first_submitted>
  <study_first_submitted_qc>August 31, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 5, 2017</study_first_posted>
  <last_update_submitted>October 10, 2022</last_update_submitted>
  <last_update_submitted_qc>October 10, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">October 12, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Maryland, Baltimore</investigator_affiliation>
    <investigator_full_name>L. Elliot Hong</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Inflammation</mesh_term>
    <mesh_term>Schizophrenia</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/NCT03271814
org study id: HP-00076657
nct id: NCT03271814
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
In a double-blinded, randomized, parallel controlled design, patients with schizophrenia
      spectrum disorder will be exposed to a single dose of lipopolysaccharide (LPS) (LPS-patient).
      Clinical symptoms, blood samples, and brain imaging will be assessed at baseline and after
      LPS. There will be two comparison groups. Comparison groups include an age- and sex-matched
      healthy control group also exposed to the same LPS (LPS-control), and an age- and sex-matched
      sample of patients with schizophrenia on placebo (Placebo-patient). As in Phase I studies,
      multiple interim analyses are expected so the current design may be modified, which will be
      communicated during annual reports (21CFR312.30).
Schizophrenia spectrum disorders are a major public health burden due to functional and
      cognitive impairment, psychosis and other symptoms, and high comorbidity. Unfortunately,
      current therapies have limited effectiveness in treating some of the symptoms and most of the
      cognitive deficits. Alternative biological models of the disease are needed for developing
      new and more effective treatment. Neuroinflammation has increasingly been implicated in the
      pathophysiology of schizophrenia. Patients with schizophrenia have signs of low-grade,
      chronic inflammation, including elevated blood levels of pro-inflammatory cytokines and other
      immune markers. Administration of LPS is the standard immune challenge to investigate the
      body's immune response in a wide range of disorders. Our goal is to use LPS to investigate
      whether schizophrenia patients have abnormal immune response to LPS and whether the
      abnormality is associated with specific brain imaging biomarkers.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Basic Science
masking: Triple (Participant, Investigator, Outcomes Assessor)
measure: IL-6
time frame: Hourly for 6 hours
description: Cytokine IL-6 at baseline and response to LPS challenge (to be reported in pg/ml or IU/ml)
measure: Brain imaging structure and function via MRI
time frame: 3 to 6 hours
description: Brain imaging at baseline and response to LPS challenge (to be reported in institutional units)
arm group label: LPS-Patient
arm group type: Experimental
description: Schizophrenia patients who are randomized to receive LPS injection.
arm group label: LPS-Healthy
arm group type: Active Comparator
description: Healthy controls who are randomized to receive LPS injection.
arm group label: Placebo-Patient
arm group type: Placebo Comparator
description: Schizophrenia patients who are randomized to receive placebo injection.
intervention type: Biological
intervention name: LPS
description: 0.6 by/kg LPS single dose iv
arm group label: LPS-Healthy
arm group label: LPS-Patient
intervention type: Other
intervention name: Placebo
description: Sterile Water
arm group label: Placebo-Patient
criteria: 
gender: All
minimum age: 15 Years
maximum age: 55 Years
healthy volunteers: Accepts Healthy Volunteers
last name: L E Hong, M.D.
role: Principal Investigator
affiliation: University of Maryland, Baltimore
last name: Judy Liu, RN, MSN
phone: 410-402-6832
email: jliu@mprc.umaryland.edu
last name: Dawn R Detamore
phone: 410-402-6820
email: ddetamor@mprc.umaryland.edu
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: University of Maryland, Baltimore
investigator full name: L. Elliot Hong
investigator title: Professor
mesh term: Inflammation
mesh term: Schizophrenia