<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/NCT01681849</url>
  </required_header>
  <id_info>
    <org_study_id>IRB00000857</org_study_id>
    <secondary_id>R01MH056120</secondary_id>
    <nct_id>NCT01681849</nct_id>
  </id_info>
  <brief_title>Neural Circuits in Women With Abuse and Posttraumatic Stress Disorder</brief_title>
  <official_title>Neural Circuits in Women With Abuse and Posttraumatic Stress Disorder</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Emory University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Institute of Mental Health (NIMH)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>Emory University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study was to assess the effects of the medication paroxetine on symptoms&#xD;
      of posttraumatic stress disorder (PTSD) and the brain in women with a history of PTSD related&#xD;
      to childhood abuse. The hypothesis is that paroxetine will result in an improvement in PTSD&#xD;
      symptoms accompanied by changes in brain functional response to reminders of childhood&#xD;
      trauma.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The main purpose of this study was to look at the effects of paroxetine on PTSD symptoms and&#xD;
      brain function in women with posttraumatic stress disorder (PTSD) related to childhood abuse.&#xD;
      Participants underwent baseline assessment with of PTSD symptoms measured with the Clinician&#xD;
      Administered PTSD Scale (CAPS) and brain function during exposure to traumatic scripts of&#xD;
      childhood abuse. Participants then were treated in a randomized double-blind fashion with&#xD;
      paroxetine or placebo for three months, followed by a repeat of these assessments.&#xD;
&#xD;
      Specific Aims of this proposal were therefore to:&#xD;
&#xD;
        -  Assess the effects of paroxetine on PTSD symptoms&#xD;
&#xD;
        -  Assess the effects of paroxetine on brain function in conjunction with exposure to&#xD;
           traumatic scripts using positron emission tomography (PET) with O-15 water&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>July 2009</start_date>
  <completion_date type="Actual">July 2015</completion_date>
  <primary_completion_date type="Actual">July 2015</primary_completion_date>
  <phase>Phase 4</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>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Mean Clinical Administered PTSD Scale for DSM-IV (CAPS) Score</measure>
    <time_frame>Baseline, End of Study (Up to 52 Weeks)</time_frame>
    <description>The CAPS is a 30-item questionnaire of PTSD symptomatology that provides continuous measures of symptom severity and frequency. CAPS-IV total symptom severity score is calculated by summing severity scores for the 17 DSM-IV PTSD symptoms. Each symptom is rated for severity based on frequency and intensity on a scale of 0-4 for a total possible severity score per symptom of 8. Criterion E (items 18-19) is duration of symptoms (minimum of one month to make the diagnosis). Items 20-30 are optional. CAPS score is based on items 1-17, CAPS score has a potential range of 0-136, with higher scores indicating greater severity of PTSD symptoms. CAPS was performed before and after treatment with paroxetine or placebo in PTSD patients.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in Brain Blood Flow Assessed by Statistical Parametric Mapping (SPM)</measure>
    <time_frame>Baseline, 3 Months Post Treatment</time_frame>
    <description>Participants were exposed to traumatic scripts versus neutral scripts before and after treatment with paroxetine or placebo. Brain blood flow was measured using statistical parametric mapping (SPM) which analyzes brain imaging data sequences. Statistical Parametric Mapping software is only capable of producing a single z-score for each Arm/Group. Data for each participant can not be generated using this software and therefore are not available to summarize in the data table below. Regional blood flow was compared for stress and neutral conditions and before and after treatment with paroxetine or placebo. Higher z-scores indicate an increase in regional blood flow to the medial prefrontal cortex under stress conditions for the 3 month time point relative to baseline. Statistical Parametric Mapping software is only capable of producing a single z-score for each Arm/Group.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">91</enrollment>
  <condition>PTSD</condition>
  <arm_group>
    <arm_group_label>Paroxetine Group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Women who have experienced early childhood abuse and have PTSD will be randomized in a double blind fashion to receive paroxetine for a three month period followed by an open label phase of three months.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo Group</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Women who have experienced early childhood abuse and have PTSD will be randomized in a double blind fashion to receive placebo for a three month period followed by an open label phase of paroxetine for three months.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>PTSD Negative</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Women who have experienced early childhood abuse and do not have PTSD will serve as a control group and complete baseline assessments. They do not undergo intervention therefore they are assessed at baseline only.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Following a three month double blind phase, subjects will be treated with open label paroxetine at a variable dosage of 10-40 mg to reach individual therapeutic levels for three months.</description>
    <arm_group_label>Placebo Group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Paroxetine</intervention_name>
    <description>Following a three month double blind phase, subjects will be treated with open label paroxetine at a variable dosage of 10-40 mg to reach individual therapeutic levels for three months.</description>
    <arm_group_label>Paroxetine Group</arm_group_label>
    <arm_group_label>Placebo Group</arm_group_label>
    <other_name>Paxil</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Positron Emission Tomography (PET) Imaging</intervention_name>
    <description>Participants will undergo positron emission tomography (PET) imaging of the brain with O-15 radiolabelled water with exposure to traumatic scripts</description>
    <arm_group_label>PTSD Negative</arm_group_label>
    <arm_group_label>Paroxetine Group</arm_group_label>
    <arm_group_label>Placebo Group</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Subjects meet criteria for current PTSD as determined by the Structured Clinical&#xD;
             Interview for DSMIV (SCID) interview for PTSD and the Clinician Administered PTSD&#xD;
             Scale (CAPS) and have a score of greater than 60 on the CAPS&#xD;
&#xD;
          -  history of penetrative sexual abuse which occurred once a month or more, for a period&#xD;
             of greater than a year at some time between the ages of 4-13, as assessed by the Early&#xD;
             Trauma Inventory (ETI)&#xD;
&#xD;
          -  are free of psychotropic medication for four weeks before the study (subjects will not&#xD;
             be taken off of medication for the purpose of the study).&#xD;
&#xD;
          -  Non-PTSD subjects will be included based on the same criteria with the exception that&#xD;
             they do not meet criteria for PTSD.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  a history of shrapnel or other foreign bodies which would preclude MRI scanning&#xD;
&#xD;
          -  meningitis&#xD;
&#xD;
          -  traumatic brain injury&#xD;
&#xD;
          -  neurological disorder or organic mental disorder&#xD;
&#xD;
          -  history of loss of consciousness&#xD;
&#xD;
          -  alcohol abuse or substance abuse or dependence based on the SCID within the past 24&#xD;
             months&#xD;
&#xD;
          -  positive pregnancy test as measured by a serum beta-HCG or urine pregnancy test on the&#xD;
             morning of the PET scan. Women will be counseled about the risks of pregnancy during&#xD;
             the course of the study&#xD;
&#xD;
          -  current or lifetime history of schizophrenia, schizoaffective disorder, or bulimia,&#xD;
             based on the SCID&#xD;
&#xD;
          -  a history of serious medical or neurological illness, such as cardiovascular,&#xD;
             gastrointestinal, hepatic, renal, neurologic or other systemic illness&#xD;
&#xD;
          -  evidence of a major medical or neurological illness on physical examination or as a&#xD;
             result of laboratory studies (CBC, BUN, creatinine, blood sugar, electrolytes, liver&#xD;
             and thyroid function tests, urinalysis, and EKG)&#xD;
&#xD;
          -  positive urine toxicology screen&#xD;
&#xD;
          -  history of ongoing violence such as domestic abuse as measured by the ETI-lifetime&#xD;
&#xD;
          -  post-menopausal status as measured by menstrual history.&#xD;
&#xD;
          -  Non-PTSD subjects will additionally be excluded with current major depression or other&#xD;
             major psychiatric disorder based on the SCID.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>James D. Bremner, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Professor</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Emory University</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30306</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>June 2017</verification_date>
  <study_first_submitted>September 6, 2012</study_first_submitted>
  <study_first_submitted_qc>September 6, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 10, 2012</study_first_posted>
  <results_first_submitted>November 28, 2016</results_first_submitted>
  <results_first_submitted_qc>June 26, 2017</results_first_submitted_qc>
  <results_first_posted type="Actual">June 28, 2017</results_first_posted>
  <last_update_submitted>June 26, 2017</last_update_submitted>
  <last_update_submitted_qc>June 26, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">June 28, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Emory University</investigator_affiliation>
    <investigator_full_name>J. Douglas Bremner, M.D.</investigator_full_name>
    <investigator_title>Professor of Psychiatry and Radiology</investigator_title>
  </responsible_party>
  <keyword>PTSD</keyword>
  <keyword>childhood abuse</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Stress Disorders, Post-Traumatic</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Paroxetine</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Participants were recruited from the Emory Clinic and Emory University Hospitals from September 2006 to November 2013.</recruitment_details>
      <pre_assignment_details>Of the 91 participants who were consented, 7 were excluded due to not meeting screening criteria.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Paroxetine Group</title>
          <description>Women who have experienced early childhood abuse and have PTSD were randomized in a double blind fashion to receive paroxetine for a three month period followed by an open label phase of three months.&#xD;
Paroxetine: Following a three month double blind phase, subjects were treated with open label paroxetine at a variable dosage of 10-40 mg to reach individual therapeutic levels for three months.&#xD;
Positron Emission Tomography (PET) Imaging: Participants underwent positron emission tomography (PET) imaging of the brain with O-15 radiolabelled water while completing memory tasks.</description>
        </group>
        <group group_id="P2">
          <title>Placebo Group</title>
          <description>Women who have experienced early childhood abuse and have PTSD were randomized in a double blind fashion to receive placebo for a three month period followed by an open label phase of paroxetine for three months.&#xD;
Placebo: Following a three month double blind phase, subjects were treated with open label paroxetine at a variable dosage of 10-40 mg to reach individual therapeutic levels for three months.&#xD;
Paroxetine: Following a three month double blind phase, subjects were treated with open label paroxetine at a variable dosage of 10-40 mg to reach individual therapeutic levels for three months.&#xD;
Positron Emission Tomography (PET) Imaging: Participants underwent positron emission tomography (PET) imaging of the brain with O-15 radiolabelled water while completing memory tasks.</description>
        </group>
        <group group_id="P3">
          <title>PTSD Negative</title>
          <description>Women who have experienced early childhood abuse and do not have PTSD served as a control group and completed baseline assessments&#xD;
Positron Emission Tomography (PET) Imaging: Participants underwent positron emission tomography (PET) imaging of the brain with O-15 radiolabelled water while completing memory tasks.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="15"/>
                <participants group_id="P2" count="13"/>
                <participants group_id="P3" count="56"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="7"/>
                <participants group_id="P2" count="6"/>
                <participants group_id="P3" count="17"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="8"/>
                <participants group_id="P2" count="7"/>
                <participants group_id="P3" count="39"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Protocol Violation</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="5"/>
                <participants group_id="P3" count="33"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="2"/>
                <participants group_id="P3" count="6"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Paroxetine Group</title>
          <description>Women who have experienced early childhood abuse and have PTSD were randomized in a double blind fashion to receive paroxetine for a three month period followed by an open label phase of three months.&#xD;
Paroxetine: Following a three month double blind phase, subjects were treated with open label paroxetine at a variable dosage of 10-40 mg to reach individual therapeutic levels for three months.&#xD;
Positron Emission Tomography (PET) Imaging: Participants underwent positron emission tomography (PET) imaging of the brain with O-15 radiolabelled water while completing memory tasks.</description>
        </group>
        <group group_id="B2">
          <title>Placebo Group</title>
          <description>Women who have experienced early childhood abuse and have PTSD were randomized in a double blind fashion to receive placebo for a three month period followed by an open label phase of paroxetine for three months.&#xD;
Placebo: Following a three month double blind phase, subjects were treated with open label paroxetine at a variable dosage of 10-40 mg to reach individual therapeutic levels for three months.&#xD;
Paroxetine: Following a three month double blind phase, subjects were treated with open label paroxetine at a variable dosage of 10-40 mg to reach individual therapeutic levels for three months.&#xD;
Positron Emission Tomography (PET) Imaging: Participants underwent positron emission tomography (PET) imaging of the brain with O-15 radiolabelled water while completing memory tasks.</description>
        </group>
        <group group_id="B3">
          <title>PTSD Negative</title>
          <description>Women who have experienced early childhood abuse and do not have PTSD served as a control group and completed baseline assessments&#xD;
Positron Emission Tomography (PET) Imaging: Participants underwent positron emission tomography (PET) imaging of the brain with O-15 radiolabelled water while completing memory tasks.</description>
        </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="15"/>
            <count group_id="B2" value="13"/>
            <count group_id="B3" value="56"/>
            <count group_id="B4" value="84"/>
          </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="15"/>
                    <measurement group_id="B2" value="13"/>
                    <measurement group_id="B3" value="56"/>
                    <measurement group_id="B4" value="84"/>
                  </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="15"/>
                    <measurement group_id="B2" value="13"/>
                    <measurement group_id="B3" value="56"/>
                    <measurement group_id="B4" value="84"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</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>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="15"/>
                    <measurement group_id="B2" value="13"/>
                    <measurement group_id="B3" value="56"/>
                    <measurement group_id="B4" value="84"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Mean Clinical Administered PTSD Scale for DSM-IV (CAPS) Score</title>
        <description>The CAPS is a 30-item questionnaire of PTSD symptomatology that provides continuous measures of symptom severity and frequency. CAPS-IV total symptom severity score is calculated by summing severity scores for the 17 DSM-IV PTSD symptoms. Each symptom is rated for severity based on frequency and intensity on a scale of 0-4 for a total possible severity score per symptom of 8. Criterion E (items 18-19) is duration of symptoms (minimum of one month to make the diagnosis). Items 20-30 are optional. CAPS score is based on items 1-17, CAPS score has a potential range of 0-136, with higher scores indicating greater severity of PTSD symptoms. CAPS was performed before and after treatment with paroxetine or placebo in PTSD patients.</description>
        <time_frame>Baseline, End of Study (Up to 52 Weeks)</time_frame>
        <population>Data for participants who completed all study visits were analyzed.</population>
        <group_list>
          <group group_id="O1">
            <title>Paroxetine Group</title>
            <description>Women who have experienced early childhood abuse and have PTSD were randomized in a double blind fashion to receive paroxetine for a three month period followed by an open label phase of three months.&#xD;
Paroxetine: Following a three month double blind phase, subjects were treated with open label paroxetine at a variable dosage of 10-40 mg to reach individual therapeutic levels for three months.&#xD;
Positron Emission Tomography (PET) Imaging: Participants underwent positron emission tomography (PET) imaging of the brain with O-15 radiolabelled water while completing memory tasks.</description>
          </group>
          <group group_id="O2">
            <title>Placebo Group</title>
            <description>Women who have experienced early childhood abuse and have PTSD were randomized in a double blind fashion to receive placebo for a three month period followed by an open label phase of paroxetine for three months.&#xD;
Placebo: Following a three month double blind phase, subjects were treated with open label paroxetine at a variable dosage of 10-40 mg to reach individual therapeutic levels for three months.&#xD;
Paroxetine: Following a three month double blind phase, subjects were treated with open label paroxetine at a variable dosage of 10-40 mg to reach individual therapeutic levels for three months.&#xD;
Positron Emission Tomography (PET) Imaging: Participants underwent positron emission tomography (PET) imaging of the brain with O-15 radiolabelled water while completing memory tasks.</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Clinical Administered PTSD Scale for DSM-IV (CAPS) Score</title>
          <description>The CAPS is a 30-item questionnaire of PTSD symptomatology that provides continuous measures of symptom severity and frequency. CAPS-IV total symptom severity score is calculated by summing severity scores for the 17 DSM-IV PTSD symptoms. Each symptom is rated for severity based on frequency and intensity on a scale of 0-4 for a total possible severity score per symptom of 8. Criterion E (items 18-19) is duration of symptoms (minimum of one month to make the diagnosis). Items 20-30 are optional. CAPS score is based on items 1-17, CAPS score has a potential range of 0-136, with higher scores indicating greater severity of PTSD symptoms. CAPS was performed before and after treatment with paroxetine or placebo in PTSD patients.</description>
          <population>Data for participants who completed all study visits were analyzed.</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
                <count group_id="O2" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="31" spread="10"/>
                    <measurement group_id="O2" value="30" spread="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>End of Study (Up to 52 Weeks)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="20" spread="10"/>
                    <measurement group_id="O2" value="25" spread="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Brain Blood Flow Assessed by Statistical Parametric Mapping (SPM)</title>
        <description>Participants were exposed to traumatic scripts versus neutral scripts before and after treatment with paroxetine or placebo. Brain blood flow was measured using statistical parametric mapping (SPM) which analyzes brain imaging data sequences. Statistical Parametric Mapping software is only capable of producing a single z-score for each Arm/Group. Data for each participant can not be generated using this software and therefore are not available to summarize in the data table below. Regional blood flow was compared for stress and neutral conditions and before and after treatment with paroxetine or placebo. Higher z-scores indicate an increase in regional blood flow to the medial prefrontal cortex under stress conditions for the 3 month time point relative to baseline. Statistical Parametric Mapping software is only capable of producing a single z-score for each Arm/Group.</description>
        <time_frame>Baseline, 3 Months Post Treatment</time_frame>
        <population>Statistical analyses yielded image data sets in which the values assigned to individual voxels correspond to the t-statistic of the difference in brain blood flow between conditions. Statistical images were displayed with values of z score units.</population>
        <group_list>
          <group group_id="O1">
            <title>Paroxetine Group</title>
            <description>Women who have experienced early childhood abuse and have PTSD were randomized in a double blind fashion to receive paroxetine for a three month period followed by an open label phase of three months.&#xD;
Paroxetine: Following a three month double blind phase, subjects were treated with open label paroxetine at a variable dosage of 10-40 mg to reach individual therapeutic levels for three months.&#xD;
Positron Emission Tomography (PET) Imaging: Participants underwent positron emission tomography (PET) imaging of the brain with O-15 radiolabelled water while completing memory tasks.</description>
          </group>
          <group group_id="O2">
            <title>Placebo Group</title>
            <description>Women who have experienced early childhood abuse and have PTSD were randomized in a double blind fashion to receive placebo for a three month period followed by an open label phase of paroxetine for three months.&#xD;
Placebo: Following a three month double blind phase, subjects were treated with open label paroxetine at a variable dosage of 10-40 mg to reach individual therapeutic levels for three months.&#xD;
Paroxetine: Following a three month double blind phase, subjects were treated with open label paroxetine at a variable dosage of 10-40 mg to reach individual therapeutic levels for three months.&#xD;
Positron Emission Tomography (PET) Imaging: Participants underwent positron emission tomography (PET) imaging of the brain with O-15 radiolabelled water while completing memory tasks.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Brain Blood Flow Assessed by Statistical Parametric Mapping (SPM)</title>
          <description>Participants were exposed to traumatic scripts versus neutral scripts before and after treatment with paroxetine or placebo. Brain blood flow was measured using statistical parametric mapping (SPM) which analyzes brain imaging data sequences. Statistical Parametric Mapping software is only capable of producing a single z-score for each Arm/Group. Data for each participant can not be generated using this software and therefore are not available to summarize in the data table below. Regional blood flow was compared for stress and neutral conditions and before and after treatment with paroxetine or placebo. Higher z-scores indicate an increase in regional blood flow to the medial prefrontal cortex under stress conditions for the 3 month time point relative to baseline. Statistical Parametric Mapping software is only capable of producing a single z-score for each Arm/Group.</description>
          <population>Statistical analyses yielded image data sets in which the values assigned to individual voxels correspond to the t-statistic of the difference in brain blood flow between conditions. Statistical images were displayed with values of z score units.</population>
          <units>z-scores</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
                <count group_id="O2" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="22"/>
                    <measurement group_id="O2" value="2.68"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse events were collected for the duration of the study and open label period (2 years). Adverse events were collected for all participants who began the study.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Paroxetine Group</title>
          <description>Women who have experienced early childhood abuse and have PTSD will be randomized in a double blind fashion to receive paroxetine for a three month period followed by an open label phase of three months.&#xD;
Paroxetine: Following a three month double blind phase, subjects will be treated with open label paroxetine at a variable dosage of 10-40 mg to reach individual therapeutic levels for three months.&#xD;
Positron Emission Tomography (PET) Imaging: Participants will undergo positron emission tomography (PET) imaging of the brain with O-15 radiolabelled water while completing memory tasks.</description>
        </group>
        <group group_id="E2">
          <title>Placebo Group</title>
          <description>Women who have experienced early childhood abuse and have PTSD will be randomized in a double blind fashion to receive placebo for a three month period followed by an open label phase of paroxetine for three months.&#xD;
Placebo: Following a three month double blind phase, subjects will be treated with open label paroxetine at a variable dosage of 10-40 mg to reach individual therapeutic levels for three months.&#xD;
Paroxetine: Following a three month double blind phase, subjects will be treated with open label paroxetine at a variable dosage of 10-40 mg to reach individual therapeutic levels for three months.&#xD;
Positron Emission Tomography (PET) Imaging: Participants will undergo positron emission tomography (PET) imaging of the brain with O-15 radiolabelled water while completing memory tasks.</description>
        </group>
        <group group_id="E3">
          <title>PTSD Negative</title>
          <description>Women who have experienced early childhood abuse and do not have PTSD will serve as a control group and complete baseline assessments&#xD;
Positron Emission Tomography (PET) Imaging: Participants will undergo positron emission tomography (PET) imaging of the brain with O-15 radiolabelled water while completing memory tasks.</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="15"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="56"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="56"/>
              </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="15"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="56"/>
              </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>Dr. J. Douglas Bremner</name_or_title>
      <organization>Emory University</organization>
      <phone>404-712-9569</phone>
      <email>doug.bremner@emory.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/NCT01681849
org study id: IRB00000857
secondary id: R01MH056120
nct id: NCT01681849
lead sponsor: 
collaborator: 
has dmc: Yes
The purpose of this study was to assess the effects of the medication paroxetine on symptoms
      of posttraumatic stress disorder (PTSD) and the brain in women with a history of PTSD related
      to childhood abuse. The hypothesis is that paroxetine will result in an improvement in PTSD
      symptoms accompanied by changes in brain functional response to reminders of childhood
      trauma.
The main purpose of this study was to look at the effects of paroxetine on PTSD symptoms and
      brain function in women with posttraumatic stress disorder (PTSD) related to childhood abuse.
      Participants underwent baseline assessment with of PTSD symptoms measured with the Clinician
      Administered PTSD Scale (CAPS) and brain function during exposure to traumatic scripts of
      childhood abuse. Participants then were treated in a randomized double-blind fashion with
      paroxetine or placebo for three months, followed by a repeat of these assessments.

      Specific Aims of this proposal were therefore to:

        -  Assess the effects of paroxetine on PTSD symptoms

        -  Assess the effects of paroxetine on brain function in conjunction with exposure to
           traumatic scripts using positron emission tomography (PET) with O-15 water
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Mean Clinical Administered PTSD Scale for DSM-IV (CAPS) Score
time frame: Baseline, End of Study (Up to 52 Weeks)
description: The CAPS is a 30-item questionnaire of PTSD symptomatology that provides continuous measures of symptom severity and frequency. CAPS-IV total symptom severity score is calculated by summing severity scores for the 17 DSM-IV PTSD symptoms. Each symptom is rated for severity based on frequency and intensity on a scale of 0-4 for a total possible severity score per symptom of 8. Criterion E (items 18-19) is duration of symptoms (minimum of one month to make the diagnosis). Items 20-30 are optional. CAPS score is based on items 1-17, CAPS score has a potential range of 0-136, with higher scores indicating greater severity of PTSD symptoms. CAPS was performed before and after treatment with paroxetine or placebo in PTSD patients.
measure: Change in Brain Blood Flow Assessed by Statistical Parametric Mapping (SPM)
time frame: Baseline, 3 Months Post Treatment
description: Participants were exposed to traumatic scripts versus neutral scripts before and after treatment with paroxetine or placebo. Brain blood flow was measured using statistical parametric mapping (SPM) which analyzes brain imaging data sequences. Statistical Parametric Mapping software is only capable of producing a single z-score for each Arm/Group. Data for each participant can not be generated using this software and therefore are not available to summarize in the data table below. Regional blood flow was compared for stress and neutral conditions and before and after treatment with paroxetine or placebo. Higher z-scores indicate an increase in regional blood flow to the medial prefrontal cortex under stress conditions for the 3 month time point relative to baseline. Statistical Parametric Mapping software is only capable of producing a single z-score for each Arm/Group.
arm group label: Paroxetine Group
arm group type: Experimental
description: Women who have experienced early childhood abuse and have PTSD will be randomized in a double blind fashion to receive paroxetine for a three month period followed by an open label phase of three months.
arm group label: Placebo Group
arm group type: Placebo Comparator
description: Women who have experienced early childhood abuse and have PTSD will be randomized in a double blind fashion to receive placebo for a three month period followed by an open label phase of paroxetine for three months.
arm group label: PTSD Negative
arm group type: Other
description: Women who have experienced early childhood abuse and do not have PTSD will serve as a control group and complete baseline assessments. They do not undergo intervention therefore they are assessed at baseline only.
intervention type: Drug
intervention name: Placebo
description: Following a three month double blind phase, subjects will be treated with open label paroxetine at a variable dosage of 10-40 mg to reach individual therapeutic levels for three months.
arm group label: Placebo Group
intervention type: Drug
intervention name: Paroxetine
description: Following a three month double blind phase, subjects will be treated with open label paroxetine at a variable dosage of 10-40 mg to reach individual therapeutic levels for three months.
arm group label: Paroxetine Group
arm group label: Placebo Group
other name: Paxil
intervention type: Other
intervention name: Positron Emission Tomography (PET) Imaging
description: Participants will undergo positron emission tomography (PET) imaging of the brain with O-15 radiolabelled water with exposure to traumatic scripts
arm group label: PTSD Negative
arm group label: Paroxetine Group
arm group label: Placebo Group
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: Accepts Healthy Volunteers
last name: James D. Bremner, MD
role: Principal Investigator
affiliation: Professor
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Emory University
investigator full name: J. Douglas Bremner, M.D.
investigator title: Professor of Psychiatry and Radiology
mesh term: Stress Disorders, Post-Traumatic
mesh term: Paroxetine
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 