<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/NCT02234687</url>
  </required_header>
  <id_info>
    <org_study_id>13-00609</org_study_id>
    <nct_id>NCT02234687</nct_id>
  </id_info>
  <brief_title>A mGlu2/3 Agonist in the Treatment of PTSD</brief_title>
  <official_title>A mGlu2/3 Agonist in the Treatment of PTSD</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>NYU Langone Health</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>NYU Langone Health</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>
  </oversight_info>
  <brief_summary>
    <textblock>
      In this study, we propose to employ a randomized, double-blind, placebo-controlled,&#xD;
      outpatient clinical trial to test the efficacy, safety, and tolerability of a 160 mg and 40&#xD;
      mg challenge of the mGlu2/3 agonist pomaglumetad methionil relative to placebo in modulating&#xD;
      fear-potentiated startle response and behavior in adults with post-traumatic stress disorder&#xD;
      (PTSD) (N=30). Each participant will receive a single dose of the study drug (40 mg vs 160 mg&#xD;
      vs placebo in a 1:1:1 ratio).&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    The original PI, Alexander Neumeister, left NYULMC. No data was analyzed.&#xD;
  </why_stopped>
  <start_date type="Actual">September 2014</start_date>
  <completion_date type="Actual">September 11, 2016</completion_date>
  <primary_completion_date type="Actual">February 11, 2016</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>Treatment</primary_purpose>
    <masking>Double (Participant, Care Provider)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>To Evaluate the Effect of 160mg and 40mg of Pomaglumetad Methionil</measure>
    <time_frame>6 months</time_frame>
    <description>To evaluate the effect of 160mg and 40mg challenge of the mGlu2/3 receptor agonist pomaglumetad methionil relative to placebo in mitigating fear-potentiated startle using the neutral-predictable-unpredictable fear-potentiated startle paradigm in adults with post-traumatic stress disorder (PTSD). The primary index of unpredictable fear will be the difference score between startle magnitude in safe and unpredictable conditions in the absence of the cue.</description>
  </primary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">10</enrollment>
  <condition>Post-traumatic Stress Disorder</condition>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo, one dose</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Pomaglumetad Methionil 40mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Pomaglumetad Methionil 40mg, one dose, one time</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Pomaglumetad Methionil 160mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Pomaglumetad Methionil 160mg, one dose, one time</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Pomaglumetad Methionil 160mg</intervention_name>
    <description>Pomaglumetad Methionil 160mg, one dose, one time</description>
    <arm_group_label>Pomaglumetad Methionil 160mg</arm_group_label>
    <other_name>LY2140023</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Pomaglumetad Methionil 40mg</intervention_name>
    <description>Pomaglumetad Methionil 40mg, one dose, one time</description>
    <arm_group_label>Pomaglumetad Methionil 40mg</arm_group_label>
    <other_name>LY2140023</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo, one dose, one time</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Men and women between 18 and 60 years of age, any race&#xD;
&#xD;
          -  Primary, current Axis I diagnosis of post traumatic stress disorder (PTSD) according&#xD;
             to Diagnostic and Statistical Manual of Mental Disorders - IV (DSM-IV) criteria&#xD;
&#xD;
          -  Able to provide written informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Past or current presence of psychotic symptoms, or diagnosis of a lifetime psychotic&#xD;
             disorder including schizophrenia, schizoaffective disorder, bipolar disorder&#xD;
&#xD;
          -  History of moderate or severe traumatic brain injury (TBI) with loss of consciousness&#xD;
&#xD;
          -  Lifetime history of seizure disorder&#xD;
&#xD;
          -  Current diagnosis of obsessive-compulsive disorder (OCD)&#xD;
&#xD;
          -  Current diagnosis of bulimia nervosa or anorexia nervosa; or substance use disorder&#xD;
&#xD;
          -  Alcohol or drug abuse in the past 90 days, or dependence in the past year.&#xD;
&#xD;
          -  Individuals with a cumulative lifetime history of intravenous substance abuse longer&#xD;
             than 1 year.&#xD;
&#xD;
          -  Severe dissociation, defined as a Clinician Administered Dissociative States Scale&#xD;
             (CADSS) score greater than 60 at baseline&#xD;
&#xD;
          -  Patients with creatinine clearance &lt;60 milliliters (mL)/min (moderate renal&#xD;
             impairment)&#xD;
&#xD;
          -  Current pregnancy or breast feeding; medical conditions that could interfere with&#xD;
             correct interpretation of study data, i.e., individuals with the following medical&#xD;
             conditions will be excluded: cancer in the past year, stroke, heart attack, angina,&#xD;
             neurological disease (multiple sclerosis, epilepsy, Parkinson's disease), central&#xD;
             nervous system (CNS) lesions including TBI with loss of consciousness, dementing&#xD;
             illness, and/or liver or kidney disease. Patients with QT interval &gt;450 msec (males)&#xD;
             and &gt;470 msec (females).&#xD;
&#xD;
          -  Participants who have started new medication regimen for PTSD within 3 months prior to&#xD;
             study start and subjects taking fluoxetine&#xD;
&#xD;
          -  Current suicidality defined by emergent Columbia Suicide Severity Rating Scale&#xD;
             (CSSRS)-defined suicidal behavior, a suicidal ideation score of 5 (indicating active&#xD;
             suicidal ideation with specific plan and some level of intent) or 4 (indicating active&#xD;
             suicidal ideation with some intent to act, without specific plan) on the CSSRS or in&#xD;
             the absence of a CSSRS suicidal ideation score of 5 or 4 or CSSRS-defined suicidal&#xD;
             behavior, if the investigator determines the patient to have a significant short-term&#xD;
             risk for a suicide attempt.&#xD;
&#xD;
          -  Individuals with active suicidal risk, active self-mutilation or aggressive behavior&#xD;
             with threatening behavior toward others within the past year, as judged by the&#xD;
             Principal Investigator&#xD;
&#xD;
          -  Pregnant or lactating women&#xD;
&#xD;
          -  Legal and Financial: Current legal proceedings resulting from the traumatic events.&#xD;
             People whose continued receipt of financial benefits is contingent upon maintaining&#xD;
             PTSD symptoms or who are waiting for a decision concerning the receipt of financial&#xD;
             benefits based upon PTSD symptoms&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Charles Marmar, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>NYU School of Medicine</affiliation>
  </overall_official>
  <removed_countries>
    <country>United States</country>
  </removed_countries>
  <verification_date>March 2018</verification_date>
  <study_first_submitted>September 3, 2014</study_first_submitted>
  <study_first_submitted_qc>September 4, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 9, 2014</study_first_posted>
  <results_first_submitted>May 4, 2016</results_first_submitted>
  <results_first_submitted_qc>March 8, 2018</results_first_submitted_qc>
  <results_first_posted type="Actual">November 2, 2018</results_first_posted>
  <last_update_submitted>March 8, 2018</last_update_submitted>
  <last_update_submitted_qc>March 8, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">November 2, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>post-traumatic stress disorder</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Stress Disorders, Traumatic</mesh_term>
    <mesh_term>Stress Disorders, Post-Traumatic</mesh_term>
  </condition_browse>

  <clinical_results>

    <participant_flow>
      <recruitment_details>No Outcome Measures Analyzed; Study Terminated</recruitment_details>
      <pre_assignment_details>No Outcome Measures Analyzed; Study Terminated</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>40 mg Poma</title>
          <description>Study Terminated. No outcome measures were analyzed</description>
        </group>
        <group group_id="P2">
          <title>Placebo</title>
          <description>Study Terminated. No outcome measures were analyzed</description>
        </group>
        <group group_id="P3">
          <title>160 mg Poma</title>
          <description>Study Terminated. No outcome measures were analyzed</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="6">Study Terminated. No outcome measures were analyzed</participants>
                <participants group_id="P2" count="4"/>
                <participants group_id="P3" count="4"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0">Study Terminated. No outcome measures were analyzed</participants>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="4"/>
                <participants group_id="P3" count="4"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Placebo</title>
        </group>
        <group group_id="B2">
          <title>40 mg Poma</title>
        </group>
        <group group_id="B3">
          <title>160 mg Poma</title>
        </group>
        <group group_id="B4">
          <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="6"/>
            <count group_id="B2" value="4"/>
            <count group_id="B3" value="4"/>
            <count group_id="B4" value="14"/>
          </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 group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="4"/>
                    <measurement group_id="B4" value="14"/>
                  </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 group_id="B4" 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="3"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="7"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>To Evaluate the Effect of 160mg and 40mg of Pomaglumetad Methionil</title>
        <description>To evaluate the effect of 160mg and 40mg challenge of the mGlu2/3 receptor agonist pomaglumetad methionil relative to placebo in mitigating fear-potentiated startle using the neutral-predictable-unpredictable fear-potentiated startle paradigm in adults with post-traumatic stress disorder (PTSD). The primary index of unpredictable fear will be the difference score between startle magnitude in safe and unpredictable conditions in the absence of the cue.</description>
        <time_frame>6 months</time_frame>
        <population>10 patients were enrolled and data for these 10 patients was not analyzed. Assuming a 2-tailed test,power=0.80, alpha=0.05, a total sample size of 30 (10 per group) is required to detect a moderate differential effect size change of a 160mg or 40 mg dose of pomaglumated methionil relative to placebo.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Placebo: Placebo, one dose, one time</description>
          </group>
          <group group_id="O2">
            <title>Pomaglumetad Methionil 160mg</title>
            <description>Pomaglumetad Methionil 160mg, one dose, one time Pomaglumetad Methionil 160mg: Pomaglumetad Methionil 160mg, one dose, one time</description>
          </group>
          <group group_id="O3">
            <title>Pomaglumetad Methionil 40mg</title>
            <description>Pomaglumetad Methionil 40mg, one dose, one time Pomaglumetad Methionil 40mg: Pomaglumetad Methionil 40mg, one dose, one time</description>
          </group>
        </group_list>
        <measure>
          <title>To Evaluate the Effect of 160mg and 40mg of Pomaglumetad Methionil</title>
          <description>To evaluate the effect of 160mg and 40mg challenge of the mGlu2/3 receptor agonist pomaglumetad methionil relative to placebo in mitigating fear-potentiated startle using the neutral-predictable-unpredictable fear-potentiated startle paradigm in adults with post-traumatic stress disorder (PTSD). The primary index of unpredictable fear will be the difference score between startle magnitude in safe and unpredictable conditions in the absence of the cue.</description>
          <population>10 patients were enrolled and data for these 10 patients was not analyzed. Assuming a 2-tailed test,power=0.80, alpha=0.05, a total sample size of 30 (10 per group) is required to detect a moderate differential effect size change of a 160mg or 40 mg dose of pomaglumated methionil relative to placebo.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
                <count group_id="O3" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>6 Months</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Placebo</title>
          <description>Placebo, one dose Placebo: Placebo, one dose, one time</description>
        </group>
        <group group_id="E2">
          <title>Pomaglumetad Methionil 160mg</title>
          <description>Pomaglumetad Methionil 160mg, one dose, one time</description>
        </group>
        <group group_id="E3">
          <title>Pomaglumetad Methionil 40mg</title>
          <description>Pomaglumetad Methionil 40mg, one dose, one time</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="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Vomiting after receiving medication</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>PTSD symptoms became worse after the study</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="4"/>
              </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>
    <limitations_and_caveats>10 patients were enrolled and data for these 10 patients was not analyzed because enrollment must reach a certain threshold for reporting.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Charles Marmar, MD</name_or_title>
      <organization>New York University School of Medicine</organization>
      <phone>646 754 4855</phone>
      <email>Charles.Marmar@nyumc.org</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/NCT02234687
org study id: 13-00609
nct id: NCT02234687
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
In this study, we propose to employ a randomized, double-blind, placebo-controlled,
      outpatient clinical trial to test the efficacy, safety, and tolerability of a 160 mg and 40
      mg challenge of the mGlu2/3 agonist pomaglumetad methionil relative to placebo in modulating
      fear-potentiated startle response and behavior in adults with post-traumatic stress disorder
      (PTSD) (N=30). Each participant will receive a single dose of the study drug (40 mg vs 160 mg
      vs placebo in a 1:1:1 ratio).
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Care Provider)
measure: To Evaluate the Effect of 160mg and 40mg of Pomaglumetad Methionil
time frame: 6 months
description: To evaluate the effect of 160mg and 40mg challenge of the mGlu2/3 receptor agonist pomaglumetad methionil relative to placebo in mitigating fear-potentiated startle using the neutral-predictable-unpredictable fear-potentiated startle paradigm in adults with post-traumatic stress disorder (PTSD). The primary index of unpredictable fear will be the difference score between startle magnitude in safe and unpredictable conditions in the absence of the cue.
arm group label: Placebo
arm group type: Placebo Comparator
description: Placebo, one dose
arm group label: Pomaglumetad Methionil 40mg
arm group type: Experimental
description: Pomaglumetad Methionil 40mg, one dose, one time
arm group label: Pomaglumetad Methionil 160mg
arm group type: Experimental
description: Pomaglumetad Methionil 160mg, one dose, one time
intervention type: Drug
intervention name: Pomaglumetad Methionil 160mg
description: Pomaglumetad Methionil 160mg, one dose, one time
arm group label: Pomaglumetad Methionil 160mg
other name: LY2140023
intervention type: Drug
intervention name: Pomaglumetad Methionil 40mg
description: Pomaglumetad Methionil 40mg, one dose, one time
arm group label: Pomaglumetad Methionil 40mg
other name: LY2140023
intervention type: Drug
intervention name: Placebo
description: Placebo, one dose, one time
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 60 Years
healthy volunteers: No
last name: Charles Marmar, MD
role: Principal Investigator
affiliation: NYU School of Medicine
country: United States
responsible party type: Sponsor
mesh term: Stress Disorders, Traumatic
mesh term: Stress Disorders, Post-Traumatic
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: 10 patients were enrolled and data for these 10 patients was not analyzed because enrollment must reach a certain threshold for reporting.
point of contact: 