<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/NCT03765138</url>
  </required_header>
  <id_info>
    <org_study_id>Research Foundation for Mental</org_study_id>
    <nct_id>NCT03765138</nct_id>
  </id_info>
  <brief_title>Combined Treatment of Prolonged Exposure and Pramipexole for Posttraumatic Stress Disorder and Depression</brief_title>
  <official_title>Combined Prolonged Exposure and Pramipexole Treatment for Patients With PTSD and Depression</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Research Foundation for Mental Hygiene, Inc.</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Research Foundation for Mental Hygiene, Inc.</source>
  <oversight_info>
    <has_dmc>No</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>
      This pilot study aims to test the safety, feasibility, and initial efficacy of combined 10&#xD;
      week treatment of prolonged exposure (PE) and Pramipexole in patients with comorbid&#xD;
      posttraumatic stress disorder (PTSD) and depression (MDD). Resting state functional&#xD;
      connectivity (rsFC) will be assessed at baseline and en of treatment.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Approximately half of the individuals with posttraumatic stress disorder (PTSD) present with&#xD;
      major depressive disorder (MDD). Compared to PTSD alone, patients with comorbid PTSD-MDD&#xD;
      demonstrate greater distress and poorer treatment outcome. Functional magnetic resonance&#xD;
      imaging (fMRI) show that relative to PTSD alone, PTSD-MDD is associated with decreased&#xD;
      resting state functional connectivity (rs-FC) in both fear- and reward-processing circuits.&#xD;
      In addition, our data suggest that Prolonged Exposure (PE), first-line PTSD treatment, may&#xD;
      successfully target impairments in the fear circuits, but not in the reward circuits, which&#xD;
      may explain the treatment-refractory quality of PTSD-MDD.&#xD;
&#xD;
      The goal of this pilot study is to test the feasibility, safety and initial efficacy of an&#xD;
      integrated therapeutic approach targeting both fear and reward impairments in PTSD-MDD&#xD;
      patients. Specifically, the investigators will examine a combination treatment with PE, shown&#xD;
      to effectively address fear circuitry deficits, and Pramipexole, a dopamine agonist, shown to&#xD;
      increase reward circuit function and to have promise in treating depression but not&#xD;
      previously studied in PTSD. The central hypothesis is that combined PE/Pramipexole will a)&#xD;
      improve PTSD and depressive symptoms in PTSD-MDD patients, and b) increase functional&#xD;
      connectivity of fear and reward pathways as measured by fMRI rs-FC. In this pilot study, 15&#xD;
      adults aged 18-60 years with PTSD-MDD will receive combined 10-week of PE and Pramipexole up&#xD;
      to the maximum dose of 4mg a day. Clinical assessment will be conducted at baseline, week 5,&#xD;
      post treatment and at 3-month follow up. Behaviorally assessments including the probabilistic&#xD;
      reward task (PRT) and attention allocation tasks, and fMRI scans for resting state functional&#xD;
      connectivity (rs-FC) will be conducted at baseline and end of treatment.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Patient recruitment difficulties&#xD;
  </why_stopped>
  <start_date type="Actual">February 19, 2019</start_date>
  <completion_date type="Actual">August 26, 2019</completion_date>
  <primary_completion_date type="Actual">August 26, 2019</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in PTSD Symptoms as Measured by the Clinician Administered PTSD Scale for DSM-5 (CAPS-5)</measure>
    <time_frame>Baseline, Week 5, Week 10, 3 month follow up</time_frame>
    <description>The CAPS is the gold standard in PTSD assessment. It is a 30-item structured interview used for current (past week or month) and lifetime diagnosis of PTSD. The CAPS was designed to be administered by clinicians and clinical researchers who have a working knowledge of PTSD. The full interview takes 45-60 minutes to administer. Scores range from 0 to 80 with higher values represent a worse outcome.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in Depressive Symptoms as Measured by the Hamilton Rating Scale for Depression (HRSD).</measure>
    <time_frame>Baseline, Week 5, Week 10, 3 month follow up</time_frame>
    <description>The Hamilton Rating Scale for Depression is a 17-item instrument that was designed to measure frequency and intensity of depressive symptoms in individuals with major depressive disorder. Ratings are made using either a five- or a three-point scale, yielding total scores from 0 to 61, with higher values represent a worse outcome.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Changes in Functional Connectivity of Fear and Reward Pathways as Measured by Functional Magentic Resonance Imaging (fMRI) Resting State Functional Connectivity (Rs-FC).</measure>
    <time_frame>baseline and week 10.</time_frame>
    <description>The investigators will use fMRI scans at baseline and posttreatment to assess connectivity in fear and reward circuits</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">1</enrollment>
  <condition>PTSD</condition>
  <condition>MDD</condition>
  <arm_group>
    <arm_group_label>PE/Pramipexole</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Experimental: Prolonged Exposure/Pramipexole Prolonged Exposure (PE) Therapy consists of 10 sessions of 90-minute duration, normally conducted once a week. In addition to receiving PE as described above, patients will have Pramipexole treatment.</description>
  </arm_group>
  <intervention>
    <intervention_type>Combination Product</intervention_type>
    <intervention_name>PE/Pramipexole</intervention_name>
    <description>Experimental: PE/Pramipexole Prolonged Exposure (PE) Therapy consists of 10 sessions of 90-minute duration, normally conducted once a week. Elements of PE include imaginal and in vivo exposure to trauma reminders; breathing retraining; cognitive restructuring; and PTSD psychoeducation.&#xD;
Pramipexole: In addition to receiving PE as described above, patients will have Pramipexole treatment. Daily dose will be started at 0.25 mg/day and increased by 0.25 mg/day every 3-4 days to a target of 2.5mg day by week 5. Beginning week 6 daily dose will be increased weekly by 0.5 mg/day to a maximum dose of 4mg. Dose will be increased as tolerated unless the patient has achieved remission and will be decreased in the event of intolerable adverse events.</description>
    <arm_group_label>PE/Pramipexole</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Males or females between the ages of 18 and 60&#xD;
&#xD;
          2. Current DSM-V diagnosis of PTSD comorbid with MDD&#xD;
&#xD;
          3. CAPS-5 ≥ 25, and 17-item HRSD ≥ 17&#xD;
&#xD;
          4. Able to give consent, fluent in English&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Prior or current diagnosis with traumatic brain injury, bipolar disorder, psychotic&#xD;
             disorder, gambling or impulse control disorders, or dementia&#xD;
&#xD;
          2. History of psychosis, psychotic disorder, mania or bipolar disorder&#xD;
&#xD;
          3. Severe substance use disorder excluding nicotine (i.e., nicotine use disorder and&#xD;
             mild-moderate alcohol/cannabis use disorder are accepted)&#xD;
&#xD;
          4. Individuals at risk for suicide based on history and current mental state. BDI-II&#xD;
             suicide item &gt; 2 or CGI-Severity baseline score of 7.&#xD;
&#xD;
          5. Treatment with antidepressants or other psychotropic medication in the past 4 weeks&#xD;
             (or 6 weeks for fluoxetine; an exception will be made for zolpidem used intermittently&#xD;
             for sleep).&#xD;
&#xD;
          6. Pregnancy or plans to become pregnant during the period of the study.&#xD;
&#xD;
          7. Current psychotherapy&#xD;
&#xD;
          8. Current unstable or untreated medical illness&#xD;
&#xD;
          9. Any condition that would exclude clinical MRI exam (e.g. pacemaker, paramagnetic&#xD;
             metallic prosthesis, surgical clips, shrapnel, necessity for constant medicinal patch,&#xD;
             some tattoos, severe obesity, claustrophobia)&#xD;
&#xD;
         10. History of untoward reaction to pramipexole&#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>Yuval Neria, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Columbia Psyhciatry and New York State Psychiatric Institute</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>New York State Psychiatric Institute</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10032</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://www.columbiapsychiatry.org/research-clinics/ptsd-research-and-treatment-program</url>
    <description>PTSD Research and Treatment Program at Columbia Psychaitry</description>
  </link>
  <verification_date>November 2019</verification_date>
  <study_first_submitted>December 2, 2018</study_first_submitted>
  <study_first_submitted_qc>December 3, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 5, 2018</study_first_posted>
  <results_first_submitted>September 19, 2019</results_first_submitted>
  <results_first_submitted_qc>November 7, 2019</results_first_submitted_qc>
  <results_first_posted type="Actual">November 26, 2019</results_first_posted>
  <last_update_submitted>November 7, 2019</last_update_submitted>
  <last_update_submitted_qc>November 7, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">November 26, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Research Foundation for Mental Hygiene, Inc.</investigator_affiliation>
    <investigator_full_name>Yuval Y Neria</investigator_full_name>
    <investigator_title>Professor of Medical Psychology</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Depression</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pramipexole</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>December 12, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/38/NCT03765138/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>PE/Pramipexole</title>
          <description>Experimental: Prolonged Exposure (PE)/Pramipexole PE Therapy consists of 10 sessions of 90-minute duration, normally conducted once a week. In addition to receiving PE as described above, patients will have Pramipexole treatment.&#xD;
PE/Pramipexole: Experimental: PE/Pramipexole PE Therapy consists of 10 sessions of 90-minute duration, normally conducted once a week. Elements of PE include imaginal and in vivo exposure to trauma reminders; breathing retraining; cognitive restructuring; and PTSD psychoeducation.&#xD;
Pramipexole: In addition to receiving PE as described above, patients will have Pramipexole treatment. Daily dose will be started at 0.25 mg/day and increased by 0.25 mg/day every 3-4 days to a target of 2.5mg day by week 5. Beginning week 6 daily dose will be increased weekly by 0.5 mg/day to a maximum dose of 4mg. Dose will be increased as tolerated unless the patient has achieved remission and will be decreased in the event of intolerance.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>PE/Pramipexole</title>
          <description>Experimental: Prolonged Exposure (PE)/Pramipexole PE Therapy consists of 10 sessions of 90-minute duration, normally conducted once a week. In addition to receiving PE as described above, patients will have Pramipexole treatment.&#xD;
PE/Pramipexole: Experimental: PE/Pramipexole PE Therapy consists of 10 sessions of 90-minute duration, normally conducted once a week. Elements of PE include imaginal and in vivo exposure to trauma reminders; breathing retraining; cognitive restructuring; and PTSD psychoeducation.&#xD;
Pramipexole: In addition to receiving PE as described above, patients will have Pramipexole treatment. Daily dose will be started at 0.25 mg/day and increased by 0.25 mg/day every 3-4 days to a target of 2.5mg day by week 5. Beginning week 6 daily dose will be increased weekly by 0.5 mg/day to a maximum dose of 4mg. Dose will be increased as tolerated unless the patient has achieved remission and will be decreased in the event of intolerance.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="1"/>
          </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_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" 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="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change in PTSD Symptoms as Measured by the Clinician Administered PTSD Scale for DSM-5 (CAPS-5)</title>
        <description>The CAPS is the gold standard in PTSD assessment. It is a 30-item structured interview used for current (past week or month) and lifetime diagnosis of PTSD. The CAPS was designed to be administered by clinicians and clinical researchers who have a working knowledge of PTSD. The full interview takes 45-60 minutes to administer. Scores range from 0 to 80 with higher values represent a worse outcome.</description>
        <time_frame>Baseline, Week 5, Week 10, 3 month follow up</time_frame>
        <population>Participant did not complete protocol.</population>
        <group_list>
          <group group_id="O1">
            <title>PE/Pramipexole</title>
            <description>Experimental: Prolonged Exposure (PE)/Pramipexole PE Therapy consists of 10 sessions of 90-minute duration, normally conducted once a week. In addition to receiving PE as described above, patients will have Pramipexole treatment.&#xD;
PE/Pramipexole: Experimental: PE/Pramipexole PE Therapy consists of 10 sessions of 90-minute duration, normally conducted once a week. Elements of PE include imaginal and in vivo exposure to trauma reminders; breathing retraining; cognitive restructuring; and PTSD psychoeducation.&#xD;
Pramipexole: In addition to receiving PE as described above, patients will have Pramipexole treatment. Daily dose will be started at 0.25 mg/day and increased by 0.25 mg/day every 3-4 days to a target of 2.5mg day by week 5. Beginning week 6 daily dose will be increased weekly by 0.5 mg/day to a maximum dose of 4mg. Dose will be increased as tolerated unless the patient has achieved remission and will be decreased in the event of intolerance.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in PTSD Symptoms as Measured by the Clinician Administered PTSD Scale for DSM-5 (CAPS-5)</title>
          <description>The CAPS is the gold standard in PTSD assessment. It is a 30-item structured interview used for current (past week or month) and lifetime diagnosis of PTSD. The CAPS was designed to be administered by clinicians and clinical researchers who have a working knowledge of PTSD. The full interview takes 45-60 minutes to administer. Scores range from 0 to 80 with higher values represent a worse outcome.</description>
          <population>Participant did not complete protocol.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Change in Depressive Symptoms as Measured by the Hamilton Rating Scale for Depression (HRSD).</title>
        <description>The Hamilton Rating Scale for Depression is a 17-item instrument that was designed to measure frequency and intensity of depressive symptoms in individuals with major depressive disorder. Ratings are made using either a five- or a three-point scale, yielding total scores from 0 to 61, with higher values represent a worse outcome.</description>
        <time_frame>Baseline, Week 5, Week 10, 3 month follow up</time_frame>
        <population>Study discontinued</population>
        <group_list>
          <group group_id="O1">
            <title>PE/Pramipexole</title>
            <description>Experimental: Prolonged Exposure/Pramipexole Prolonged Exposure (PE) Therapy consists of 10 sessions of 90-minute duration, normally conducted once a week. In addition to receiving PE as described above, patients will have Pramipexole treatment.&#xD;
PE/Pramipexole: Experimental: PE/Pramipexole Prolonged Exposure (PE) Therapy consists of 10 sessions of 90-minute duration, normally conducted once a week. Elements of PE include imaginal and in vivo exposure to trauma reminders; breathing retraining; cognitive restructuring; and PTSD psychoeducation.&#xD;
Pramipexole: In addition to receiving PE as described above, patients will have Pramipexole treatment. Daily dose will be started at 0.25 mg/day and increased by 0.25 mg/day every 3-4 days to a target of 2.5mg day by week 5. Beginning week 6 daily dose will be increased weekly by 0.5 mg/day to a maximum dose of 4mg. Dose will be increased as tolerated unless the patient has achieved remission.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Depressive Symptoms as Measured by the Hamilton Rating Scale for Depression (HRSD).</title>
          <description>The Hamilton Rating Scale for Depression is a 17-item instrument that was designed to measure frequency and intensity of depressive symptoms in individuals with major depressive disorder. Ratings are made using either a five- or a three-point scale, yielding total scores from 0 to 61, with higher values represent a worse outcome.</description>
          <population>Study discontinued</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Changes in Functional Connectivity of Fear and Reward Pathways as Measured by Functional Magentic Resonance Imaging (fMRI) Resting State Functional Connectivity (Rs-FC).</title>
        <description>The investigators will use fMRI scans at baseline and posttreatment to assess connectivity in fear and reward circuits</description>
        <time_frame>baseline and week 10.</time_frame>
        <population>Study discontinued</population>
        <group_list>
          <group group_id="O1">
            <title>PE/Pramipexole</title>
            <description>Experimental: Prolonged Exposure/Pramipexole Prolonged Exposure (PE) Therapy consists of 10 sessions of 90-minute duration, normally conducted once a week. In addition to receiving PE as described above, patients will have Pramipexole treatment.&#xD;
PE/Pramipexole: Experimental: PE/Pramipexole Prolonged Exposure (PE) Therapy consists of 10 sessions of 90-minute duration, normally conducted once a week. Elements of PE include imaginal and in vivo exposure to trauma reminders; breathing retraining; cognitive restructuring; and PTSD psychoeducation.&#xD;
Pramipexole: In addition to receiving PE as described above, patients will have Pramipexole treatment. Daily dose will be started at 0.25 mg/day and increased by 0.25 mg/day every 3-4 days to a target of 2.5mg day by week 5. Beginning week 6 daily dose will be increased weekly by 0.5 mg/day to a maximum dose of 4mg. Dose will be increased as tolerated unless the patient has achieved remission.</description>
          </group>
        </group_list>
        <measure>
          <title>Changes in Functional Connectivity of Fear and Reward Pathways as Measured by Functional Magentic Resonance Imaging (fMRI) Resting State Functional Connectivity (Rs-FC).</title>
          <description>The investigators will use fMRI scans at baseline and posttreatment to assess connectivity in fear and reward circuits</description>
          <population>Study discontinued</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Up to 5 months</time_frame>
      <group_list>
        <group group_id="E1">
          <title>PE/Pramipexole</title>
          <description>Experimental: Prolonged Exposure (PE)/Pramipexole PE Therapy consists of 10 sessions of 90-minute duration, normally conducted once a week. In addition to receiving PE as described above, patients will have Pramipexole treatment.&#xD;
PE/Pramipexole: Experimental: PE/Pramipexole PE Therapy consists of 10 sessions of 90-minute duration, normally conducted once a week. Elements of PE include imaginal and in vivo exposure to trauma reminders; breathing retraining; cognitive restructuring; and PTSD psychoeducation.&#xD;
Pramipexole: In addition to receiving PE as described above, patients will have Pramipexole treatment. Daily dose will be started at 0.25 mg/day and increased by 0.25 mg/day every 3-4 days to a target of 2.5mg day by week 5. Beginning week 6 daily dose will be increased weekly by 0.5 mg/day to a maximum dose of 4mg. Dose will be increased as tolerated unless the patient has achieved remission and will be decreased in the event of intolerance.</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="1"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
              </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="1"/>
              </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. Yuval Neria</name_or_title>
      <organization>Columbia University Medical Center/New York State Psychiatric Institute</organization>
      <phone>646-774-8092</phone>
      <email>Yuval.Neria@nyspi.columbia.edu</email>
    </point_of_contact>
  </clinical_results>
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03765138
org study id: Research Foundation for Mental
nct id: NCT03765138
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This pilot study aims to test the safety, feasibility, and initial efficacy of combined 10
      week treatment of prolonged exposure (PE) and Pramipexole in patients with comorbid
      posttraumatic stress disorder (PTSD) and depression (MDD). Resting state functional
      connectivity (rsFC) will be assessed at baseline and en of treatment.
Approximately half of the individuals with posttraumatic stress disorder (PTSD) present with
      major depressive disorder (MDD). Compared to PTSD alone, patients with comorbid PTSD-MDD
      demonstrate greater distress and poorer treatment outcome. Functional magnetic resonance
      imaging (fMRI) show that relative to PTSD alone, PTSD-MDD is associated with decreased
      resting state functional connectivity (rs-FC) in both fear- and reward-processing circuits.
      In addition, our data suggest that Prolonged Exposure (PE), first-line PTSD treatment, may
      successfully target impairments in the fear circuits, but not in the reward circuits, which
      may explain the treatment-refractory quality of PTSD-MDD.

      The goal of this pilot study is to test the feasibility, safety and initial efficacy of an
      integrated therapeutic approach targeting both fear and reward impairments in PTSD-MDD
      patients. Specifically, the investigators will examine a combination treatment with PE, shown
      to effectively address fear circuitry deficits, and Pramipexole, a dopamine agonist, shown to
      increase reward circuit function and to have promise in treating depression but not
      previously studied in PTSD. The central hypothesis is that combined PE/Pramipexole will a)
      improve PTSD and depressive symptoms in PTSD-MDD patients, and b) increase functional
      connectivity of fear and reward pathways as measured by fMRI rs-FC. In this pilot study, 15
      adults aged 18-60 years with PTSD-MDD will receive combined 10-week of PE and Pramipexole up
      to the maximum dose of 4mg a day. Clinical assessment will be conducted at baseline, week 5,
      post treatment and at 3-month follow up. Behaviorally assessments including the probabilistic
      reward task (PRT) and attention allocation tasks, and fMRI scans for resting state functional
      connectivity (rs-FC) will be conducted at baseline and end of treatment.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Change in PTSD Symptoms as Measured by the Clinician Administered PTSD Scale for DSM-5 (CAPS-5)
time frame: Baseline, Week 5, Week 10, 3 month follow up
description: The CAPS is the gold standard in PTSD assessment. It is a 30-item structured interview used for current (past week or month) and lifetime diagnosis of PTSD. The CAPS was designed to be administered by clinicians and clinical researchers who have a working knowledge of PTSD. The full interview takes 45-60 minutes to administer. Scores range from 0 to 80 with higher values represent a worse outcome.
measure: Change in Depressive Symptoms as Measured by the Hamilton Rating Scale for Depression (HRSD).
time frame: Baseline, Week 5, Week 10, 3 month follow up
description: The Hamilton Rating Scale for Depression is a 17-item instrument that was designed to measure frequency and intensity of depressive symptoms in individuals with major depressive disorder. Ratings are made using either a five- or a three-point scale, yielding total scores from 0 to 61, with higher values represent a worse outcome.
measure: Changes in Functional Connectivity of Fear and Reward Pathways as Measured by Functional Magentic Resonance Imaging (fMRI) Resting State Functional Connectivity (Rs-FC).
time frame: baseline and week 10.
description: The investigators will use fMRI scans at baseline and posttreatment to assess connectivity in fear and reward circuits
arm group label: PE/Pramipexole
arm group type: Experimental
description: Experimental: Prolonged Exposure/Pramipexole Prolonged Exposure (PE) Therapy consists of 10 sessions of 90-minute duration, normally conducted once a week. In addition to receiving PE as described above, patients will have Pramipexole treatment.
intervention type: Combination Product
intervention name: PE/Pramipexole
description: Experimental: PE/Pramipexole Prolonged Exposure (PE) Therapy consists of 10 sessions of 90-minute duration, normally conducted once a week. Elements of PE include imaginal and in vivo exposure to trauma reminders; breathing retraining; cognitive restructuring; and PTSD psychoeducation.
Pramipexole: In addition to receiving PE as described above, patients will have Pramipexole treatment. Daily dose will be started at 0.25 mg/day and increased by 0.25 mg/day every 3-4 days to a target of 2.5mg day by week 5. Beginning week 6 daily dose will be increased weekly by 0.5 mg/day to a maximum dose of 4mg. Dose will be increased as tolerated unless the patient has achieved remission and will be decreased in the event of intolerable adverse events.
arm group label: PE/Pramipexole
criteria: 
gender: All
minimum age: 18 Years
maximum age: 60 Years
healthy volunteers: No
last name: Yuval Neria, PhD
role: Principal Investigator
affiliation: Columbia Psyhciatry and New York State Psychiatric Institute
facility: 
country: United States
url: https://www.columbiapsychiatry.org/research-clinics/ptsd-research-and-treatment-program
description: PTSD Research and Treatment Program at Columbia Psychaitry
responsible party type: Principal Investigator
investigator affiliation: Research Foundation for Mental Hygiene, Inc.
investigator full name: Yuval Y Neria
investigator title: Professor of Medical Psychology
mesh term: Depression
mesh term: Pramipexole
sharing ipd: No
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 