<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/NCT03761030</url>
  </required_header>
  <id_info>
    <org_study_id>7733</org_study_id>
    <secondary_id>4R33MH110029-03</secondary_id>
    <nct_id>NCT03761030</nct_id>
  </id_info>
  <brief_title>L-DOPA vs. Placebo for Depression and Psychomotor Slowing in Older Adults</brief_title>
  <official_title>Targeting Dopaminergic Mechanisms of Slowing to Improve Late Life Depression</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>New York State Psychiatric Institute</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>New York State Psychiatric Institute</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Individuals with Late Life Depression (LLD) often have cognitive problems, particularly&#xD;
      problems with memory, attention, and problem solving, all of which contribute to&#xD;
      antidepressant non-response. Our group and others have shown that decreased thinking speed is&#xD;
      the central cause of functional problems in patients with LLD. Similarly, decreased walking&#xD;
      speed is associated with depression and carries additional risk for falls, hospitalization,&#xD;
      and death. Available evidence suggests that declining functionality in the brain's dopamine&#xD;
      system contributes to age-related cognitive and motor slowing. The central hypothesis of this&#xD;
      study is that by enhancing dopamine functioning in the brain and improving cognitive and&#xD;
      motor slowing, administration of carbidopa/levodopa (L-DOPA) will improve depressive symptoms&#xD;
      in older adults.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Enrolled participants were aged 60 and older with (1) a DSM 5 depressive disorder, (2)&#xD;
      significant depressive symptoms, and (3) decreased thinking or walking speed will receive 8&#xD;
      weeks of treatment with L-DOPA up to 450mg. We will test whether L-DOPA increases brain&#xD;
      dopamine release using neuroimaging and whether it speeds up thinking and walking speed. Data&#xD;
      collected in the proposed studies may help identify a new treatment for LLD, which could have&#xD;
      large public health ramifications given the prevalence, frequent treatment resistance, and&#xD;
      chronicity characteristic of LLD. This project also will elucidate the neurobiology of&#xD;
      slowing at molecular, structural, and functional levels of analysis, increasing our&#xD;
      understanding of the interplay between these aging-associated processes and the&#xD;
      pathophysiologic changes underlying late life neuropsychiatric disorders. Exploring patient&#xD;
      characteristics that predict response to L-DOPA may provide useful information to guide&#xD;
      differential therapeutics and develop personalized medicine for LLD.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    The project end date was reached prior to the full sample enrollment&#xD;
  </why_stopped>
  <start_date type="Actual">January 9, 2019</start_date>
  <completion_date type="Actual">September 8, 2021</completion_date>
  <primary_completion_date type="Actual">September 8, 2021</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>
    <masking_description>Double Blind</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Change From Baseline Hamilton Rating Scale for Depression 24-Item Scale to Study Completion (8 Weeks)</measure>
    <time_frame>Change from Baseline to 8 Weeks</time_frame>
    <description>The Hamilton Rating Scale for Depression (HRSD) is a 24-item questionnaire used as an indication of depression and a guide to evaluate recovery. Total scores range from 0-74, not including atypical symptoms sub-scale. A score of 16 or above is typically considered to indicate the presence of depressive symptoms. Higher scores indicate greater severity. Because the full sample was not enrolled and the results are considered unreliable, no statistical analysis was performed other than calculating means and standard deviations.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Digit Symbol Test</measure>
    <time_frame>Change from Baseline to 8 Weeks</time_frame>
    <description>The Digit Symbol test is a neuropsychological test measuring information processing speed. It consists of digit-symbol pairs (e.g. 1/-,2/┴ ... 7/Λ,8/X,9/=) followed by a list of digits. Under each digit the subject should write down the corresponding symbol as fast as possible. The number of correct symbols within the allowed time is measured. Score ranges from 0-133, with higher scores indicating higher information processing speed. Because the full sample was not enrolled and the results are considered unreliable, no statistical analysis was performed other than calculating means and standard deviations.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Single Task Gait Speed</measure>
    <time_frame>Change from Baseline to 8 Weeks</time_frame>
    <description>Patients' gait was assessed as walking speed in cm/s on a 15' walking course. Patients walked at their usual or normal speed for a total of 27' (starting and ending at a point 6 feet prior to and after the 15' course to eliminate acceleration and deceleration effects). Two trials were completed, and gait speed was based on the average of 2 trials. Because the full sample was not enrolled and the results are considered unreliable, no statistical analysis was performed other than calculating means and standard deviations.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Inventory of Depressive Symptomatology--Self Report (IDS-SR)</measure>
    <time_frame>Change from Baseline to 8 Weeks</time_frame>
    <description>The Inventory of Depressive Symptomatology--Self Report (IDS-SR) is a rating scale for depressive symptoms based on standard diagnostic criteria for Major Depressive Disorder. The scale ranges from 0-84 with higher scores indicating more severe depression. Because the full sample was not enrolled and the results are considered unreliable, no statistical analysis was performed other than calculating means and standard deviations.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pattern Comparison Test</measure>
    <time_frame>Change from Baseline to 8 Weeks</time_frame>
    <description>This test required participants to identify whether two visual patterns are the &quot;same&quot; or &quot;not the same&quot; (responses were made by pressing a &quot;yes&quot; or &quot;no&quot; button). Patterns were either identical or varied on one of three dimensions: color (all ages), adding/taking something away (all ages), or one versus many. Scores reflect the number of correct items completed in 90 s, with scores ranging from a minimum of 0 to a maximum of 30. Items were designed to minimize the number of errors that were made. Because the full sample was not enrolled and the results are considered unreliable, no statistical analysis was performed other than calculating means and standard deviations.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Letter Comparison Test</measure>
    <time_frame>Change from Baseline to 8 Weeks</time_frame>
    <description>Subjects were asked to determine whether two strings of letters are the same or different. There are 3 pages and the subject is given 30 seconds per page. Scoring is based on the number answered correctly. Scores range from 0 to 21, with the higher the number, the better the score. Because the full sample was not enrolled and the results are considered unreliable, no statistical analysis was performed other than calculating means and standard deviations.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">51</enrollment>
  <condition>Major Depressive Disorder</condition>
  <condition>Dysthymia</condition>
  <condition>Depression</condition>
  <arm_group>
    <arm_group_label>L-DOPA Arm</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Those assigned to L-DOPA will begin taking 37.5mg carbidopa/150 mg levodopa once daily (with placebo twice daily) for one week, then increase to 75mg carbidopa/300mg levodopa (37.5 mg carbidopa/150mg levodopa twice daily and placebo once daily) for one week, and finally increase to 112.5mg carbidopa/450mg levodopa (37.5 mg carbidopa/150mg levodopa three times daily and no placebo) for the final six weeks. Each subject assigned to the L-DOPA arm will be titrated to 450mg L-DOPA unless they cannot tolerate higher doses, in which case subjects will have their dosage reduced to the maximum tolerable dose</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo Arm</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Subjects assigned to the placebo arm will take placebo oral tablet three times daily throughout the study.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>L-DOPA</intervention_name>
    <description>We will be using generic sinemet 25/100 tablets in this study.</description>
    <arm_group_label>L-DOPA Arm</arm_group_label>
    <other_name>carbidopa/levodopa (Sinemet)</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo Oral Tablet</intervention_name>
    <description>25/100 placebo tablets</description>
    <arm_group_label>Placebo Arm</arm_group_label>
    <other_name>Placebo</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Aged 60 years and older&#xD;
&#xD;
          2. DSM 5 non-psychotic Major Depressive Disorder, Dysthymia, or Depression Not Otherwise&#xD;
             Specified&#xD;
&#xD;
          3. Hamilton Rating Scale for Depression (HRSD) &gt; 15&#xD;
&#xD;
          4. Decreased processing speed (defined as performance &gt; 0.5SD below age-adjusted norms on&#xD;
             Digit Symbol Substitution Test or Trail Making Test Part A) OR decreased gait speed&#xD;
             (defined as average walking speed over 15' course &lt; 1m/s)&#xD;
&#xD;
          5. Willing to and capable of providing informed consent and complying with study&#xD;
             procedures&#xD;
&#xD;
          6. Alternative standard treatments for MDD, Dysthymia, or Depression NOS (e.g.,&#xD;
             antidepressant medication or psychotherapy) have been discussed and the individual&#xD;
             agrees to be involved in an experimental treatment.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Diagnosis of substance abuse or dependence (excluding Tobacco Use Disorder) within the&#xD;
             past 12 months.&#xD;
&#xD;
          2. History of or current psychosis, psychotic disorder, mania, or bipolar disorder&#xD;
&#xD;
          3. Diagnosis of probable Alzheimer's Disease, Vascular Dementia, or Parkinson's Disease&#xD;
             (PD)&#xD;
&#xD;
          4. Mini Mental Status Exam (MMSE) &lt; 25&#xD;
&#xD;
          5. HRSD ≥ 28; HRSD suicide item &gt; 2 or the presence of significant suicide risk as judged&#xD;
             by clinician or Clinical Global Impressions (CGI)-Severity score of 7 at baseline.&#xD;
&#xD;
          6. Current or recent (within the past 4 weeks) treatment with antidepressants,&#xD;
             antipsychotics, dopaminergic agents, or mood stabilizers.&#xD;
&#xD;
          7. History of allergy, hypersensitivity reaction, or severe intolerance to L-DOPA&#xD;
&#xD;
          8. Acute, severe, or unstable medical or neurological illness&#xD;
&#xD;
          9. Mobility limiting osteoarthritis of any lower extremity joints, symptomatic lumbar&#xD;
             spine disease, mobility limiting history of joint replacement surgery, or history of&#xD;
             spine surgery&#xD;
&#xD;
             FOR SUBJECTS RECEIVING PET/MRI SCANS ONLY:&#xD;
&#xD;
         10. Having contraindication to MRI scanning (such as metal in body) or unable to tolerate&#xD;
             the scanning procedures&#xD;
&#xD;
         11. History of significant radioactivity exposure (nuclear medicine studies or&#xD;
             occupational exposure)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>60 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Bret Rutherford, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>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>
  <verification_date>May 2023</verification_date>
  <study_first_submitted>November 29, 2018</study_first_submitted>
  <study_first_submitted_qc>November 29, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 3, 2018</study_first_posted>
  <results_first_submitted>May 2, 2023</results_first_submitted>
  <results_first_submitted_qc>May 18, 2023</results_first_submitted_qc>
  <results_first_posted type="Actual">May 22, 2023</results_first_posted>
  <last_update_submitted>May 18, 2023</last_update_submitted>
  <last_update_submitted_qc>May 18, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">May 22, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>New York State Psychiatric Institute</investigator_affiliation>
    <investigator_full_name>Bret Rutherford</investigator_full_name>
    <investigator_title>Associate Professor of Clinical Psychiatry</investigator_title>
  </responsible_party>
  <keyword>Depressive symptoms</keyword>
  <keyword>Cognitive problems</keyword>
  <keyword>Antidepressant non-response</keyword>
  <keyword>Dopamine system</keyword>
  <keyword>Older Adults</keyword>
  <keyword>Motor slowing</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Depression</mesh_term>
    <mesh_term>Depressive Disorder</mesh_term>
    <mesh_term>Depressive Disorder, Major</mesh_term>
    <mesh_term>Dysthymic Disorder</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Levodopa</mesh_term>
    <mesh_term>Carbidopa</mesh_term>
    <mesh_term>Carbidopa, levodopa drug combination</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>November 28, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/30/NCT03761030/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>July 24, 2015</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/30/NCT03761030/SAP_001.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Informed Consent Form</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>November 28, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/30/NCT03761030/ICF_002.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>In total, 51 subjects were enrolled. Of the 51 enrolled, 20 subjects were found to be ineligible or did not continue in the study after enrolling. Thus, 51 participants enrolled and 31 were assigned to a treatment group and began the study.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>L-DOPA Arm</title>
          <description>Those assigned to L-DOPA will begin taking 37.5mg carbidopa/150 mg levodopa once daily (with placebo twice daily) for one week, then increase to 75mg carbidopa/300mg levodopa (37.5 mg carbidopa/150mg levodopa twice daily and placebo once daily) for one week, and finally increase to 112.5mg carbidopa/450mg levodopa (37.5 mg carbidopa/150mg levodopa three times daily and no placebo) for the final six weeks. Each subject assigned to the L-DOPA arm will be titrated to 450mg L-DOPA unless they cannot tolerate higher doses, in which case subjects will have their dosage reduced to the maximum tolerable dose&#xD;
L-DOPA: We will be using generic sinemet 25/100 tablets in this study.</description>
        </group>
        <group group_id="P2">
          <title>Placebo Arm</title>
          <description>Subjects assigned to the placebo arm will take placebo oral tablet three times daily throughout the study.&#xD;
Placebo Oral Tablet: 25/100 placebo tablets</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="16"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="13"/>
                <participants group_id="P2" count="12"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="4"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>L-DOPA Arm</title>
          <description>Those assigned to L-DOPA will begin taking 37.5mg carbidopa/150 mg levodopa once daily (with placebo twice daily) for one week, then increase to 75mg carbidopa/300mg levodopa (37.5 mg carbidopa/150mg levodopa twice daily and placebo once daily) for one week, and finally increase to 112.5mg carbidopa/450mg levodopa (37.5 mg carbidopa/150mg levodopa three times daily and no placebo) for the final six weeks. Each subject assigned to the L-DOPA arm will be titrated to 450mg L-DOPA unless they cannot tolerate higher doses, in which case subjects will have their dosage reduced to the maximum tolerable dose&#xD;
L-DOPA: We will be using generic sinemet 25/100 tablets in this study.</description>
        </group>
        <group group_id="B2">
          <title>Placebo Arm</title>
          <description>Subjects assigned to the placebo arm will take placebo oral tablet three times daily throughout the study.&#xD;
Placebo Oral Tablet: 25/100 placebo tablets</description>
        </group>
        <group group_id="B3">
          <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="16"/>
            <count group_id="B3" value="31"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="69.0" spread="7.3"/>
                    <measurement group_id="B2" value="66.7" spread="6.1"/>
                    <measurement group_id="B3" value="67.8" spread="6.7"/>
                  </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="9"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="19"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="12"/>
                  </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="1"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="13"/>
                    <measurement group_id="B2" value="11"/>
                    <measurement group_id="B3" value="24"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="2"/>
                  </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 group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="7"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="19"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" 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="16"/>
                    <measurement group_id="B3" value="31"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Hamilton Rating Scale for Depression (24 item)</title>
          <description>The Hamilton Rating Scale for Depression (HRSD) is a 24-item questionnaire used as an indication of depression and a guide to evaluate recovery. Total scores range from 0-74, not including atypical symptoms sub-scale. A score of 16 or above is typically considered to indicate the presence of depressive symptoms. Higher scores indicate greater severity.</description>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="21.1" spread="4.7"/>
                    <measurement group_id="B2" value="20.3" spread="3.9"/>
                    <measurement group_id="B3" value="20.7" spread="4.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Clinical Global Impressions--Severity</title>
          <description>The Clinical Global Impressions--Severity (CGI-S) scale measures the clinician's assessment of global illness severity. Scores range from 1 (normal, not at all ill) to 7 (among the most extremely ill patients). Higher scores denote more severe illness.</description>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="3.7" spread="0.6"/>
                    <measurement group_id="B2" value="4.3" spread="0.7"/>
                    <measurement group_id="B3" value="4.0" spread="0.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline Hamilton Rating Scale for Depression 24-Item Scale to Study Completion (8 Weeks)</title>
        <description>The Hamilton Rating Scale for Depression (HRSD) is a 24-item questionnaire used as an indication of depression and a guide to evaluate recovery. Total scores range from 0-74, not including atypical symptoms sub-scale. A score of 16 or above is typically considered to indicate the presence of depressive symptoms. Higher scores indicate greater severity. Because the full sample was not enrolled and the results are considered unreliable, no statistical analysis was performed other than calculating means and standard deviations.</description>
        <time_frame>Change from Baseline to 8 Weeks</time_frame>
        <population>Participants with Week 8 data available were analyzed.</population>
        <group_list>
          <group group_id="O1">
            <title>L-DOPA Arm</title>
            <description>Those assigned to L-DOPA will begin taking 37.5mg carbidopa/150 mg levodopa once daily (with placebo twice daily) for one week, then increase to 75mg carbidopa/300mg levodopa (37.5 mg carbidopa/150mg levodopa twice daily and placebo once daily) for one week, and finally increase to 112.5mg carbidopa/450mg levodopa (37.5 mg carbidopa/150mg levodopa three times daily and no placebo) for the final six weeks. Each subject assigned to the L-DOPA arm will be titrated to 450mg L-DOPA unless they cannot tolerate higher doses, in which case subjects will have their dosage reduced to the maximum tolerable dose&#xD;
L-DOPA: We will be using generic sinemet 25/100 tablets in this study.</description>
          </group>
          <group group_id="O2">
            <title>Placebo Arm</title>
            <description>Subjects assigned to the placebo arm will take placebo oral tablet three times daily throughout the study.&#xD;
Placebo Oral Tablet: 25/100 placebo tablets</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline Hamilton Rating Scale for Depression 24-Item Scale to Study Completion (8 Weeks)</title>
          <description>The Hamilton Rating Scale for Depression (HRSD) is a 24-item questionnaire used as an indication of depression and a guide to evaluate recovery. Total scores range from 0-74, not including atypical symptoms sub-scale. A score of 16 or above is typically considered to indicate the presence of depressive symptoms. Higher scores indicate greater severity. Because the full sample was not enrolled and the results are considered unreliable, no statistical analysis was performed other than calculating means and standard deviations.</description>
          <population>Participants with Week 8 data available 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="12"/>
                <count group_id="O2" value="13"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.2" spread="6.4"/>
                    <measurement group_id="O2" value="-3.6" spread="5.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Digit Symbol Test</title>
        <description>The Digit Symbol test is a neuropsychological test measuring information processing speed. It consists of digit-symbol pairs (e.g. 1/-,2/┴ ... 7/Λ,8/X,9/=) followed by a list of digits. Under each digit the subject should write down the corresponding symbol as fast as possible. The number of correct symbols within the allowed time is measured. Score ranges from 0-133, with higher scores indicating higher information processing speed. Because the full sample was not enrolled and the results are considered unreliable, no statistical analysis was performed other than calculating means and standard deviations.</description>
        <time_frame>Change from Baseline to 8 Weeks</time_frame>
        <population>Participants with Week 8 data available were analyzed.</population>
        <group_list>
          <group group_id="O1">
            <title>L-DOPA Arm</title>
            <description>Those assigned to L-DOPA will begin taking 37.5mg carbidopa/150 mg levodopa once daily (with placebo twice daily) for one week, then increase to 75mg carbidopa/300mg levodopa (37.5 mg carbidopa/150mg levodopa twice daily and placebo once daily) for one week, and finally increase to 112.5mg carbidopa/450mg levodopa (37.5 mg carbidopa/150mg levodopa three times daily and no placebo) for the final six weeks. Each subject assigned to the L-DOPA arm will be titrated to 450mg L-DOPA unless they cannot tolerate higher doses, in which case subjects will have their dosage reduced to the maximum tolerable dose&#xD;
L-DOPA: We will be using generic sinemet 25/100 tablets in this study.</description>
          </group>
          <group group_id="O2">
            <title>Placebo Arm</title>
            <description>Subjects assigned to the placebo arm will take placebo oral tablet three times daily throughout the study.&#xD;
Placebo Oral Tablet: 25/100 placebo tablets</description>
          </group>
        </group_list>
        <measure>
          <title>Digit Symbol Test</title>
          <description>The Digit Symbol test is a neuropsychological test measuring information processing speed. It consists of digit-symbol pairs (e.g. 1/-,2/┴ ... 7/Λ,8/X,9/=) followed by a list of digits. Under each digit the subject should write down the corresponding symbol as fast as possible. The number of correct symbols within the allowed time is measured. Score ranges from 0-133, with higher scores indicating higher information processing speed. Because the full sample was not enrolled and the results are considered unreliable, no statistical analysis was performed other than calculating means and standard deviations.</description>
          <population>Participants with Week 8 data available were analyzed.</population>
          <units>Number of items correctly completed</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="9"/>
                <count group_id="O2" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.8" spread="4.0"/>
                    <measurement group_id="O2" value="5.0" spread="3.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Single Task Gait Speed</title>
        <description>Patients' gait was assessed as walking speed in cm/s on a 15' walking course. Patients walked at their usual or normal speed for a total of 27' (starting and ending at a point 6 feet prior to and after the 15' course to eliminate acceleration and deceleration effects). Two trials were completed, and gait speed was based on the average of 2 trials. Because the full sample was not enrolled and the results are considered unreliable, no statistical analysis was performed other than calculating means and standard deviations.</description>
        <time_frame>Change from Baseline to 8 Weeks</time_frame>
        <population>Participants with Week 8 data available were analyzed</population>
        <group_list>
          <group group_id="O1">
            <title>L-DOPA Arm</title>
            <description>Those assigned to L-DOPA will begin taking 37.5mg carbidopa/150 mg levodopa once daily (with placebo twice daily) for one week, then increase to 75mg carbidopa/300mg levodopa (37.5 mg carbidopa/150mg levodopa twice daily and placebo once daily) for one week, and finally increase to 112.5mg carbidopa/450mg levodopa (37.5 mg carbidopa/150mg levodopa three times daily and no placebo) for the final six weeks. Each subject assigned to the L-DOPA arm will be titrated to 450mg L-DOPA unless they cannot tolerate higher doses, in which case subjects will have their dosage reduced to the maximum tolerable dose&#xD;
L-DOPA: We will be using generic sinemet 25/100 tablets in this study.</description>
          </group>
          <group group_id="O2">
            <title>Placebo Arm</title>
            <description>Subjects assigned to the placebo arm will take placebo oral tablet three times daily throughout the study.&#xD;
Placebo Oral Tablet: 25/100 placebo tablets</description>
          </group>
        </group_list>
        <measure>
          <title>Single Task Gait Speed</title>
          <description>Patients' gait was assessed as walking speed in cm/s on a 15' walking course. Patients walked at their usual or normal speed for a total of 27' (starting and ending at a point 6 feet prior to and after the 15' course to eliminate acceleration and deceleration effects). Two trials were completed, and gait speed was based on the average of 2 trials. Because the full sample was not enrolled and the results are considered unreliable, no statistical analysis was performed other than calculating means and standard deviations.</description>
          <population>Participants with Week 8 data available were analyzed</population>
          <units>cm/s</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
                <count group_id="O2" value="9"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.7" spread="14.9"/>
                    <measurement group_id="O2" value="-3.8" spread="14.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Inventory of Depressive Symptomatology--Self Report (IDS-SR)</title>
        <description>The Inventory of Depressive Symptomatology--Self Report (IDS-SR) is a rating scale for depressive symptoms based on standard diagnostic criteria for Major Depressive Disorder. The scale ranges from 0-84 with higher scores indicating more severe depression. Because the full sample was not enrolled and the results are considered unreliable, no statistical analysis was performed other than calculating means and standard deviations.</description>
        <time_frame>Change from Baseline to 8 Weeks</time_frame>
        <population>Participants with available Week 8 data were analyzed</population>
        <group_list>
          <group group_id="O1">
            <title>L-DOPA Arm</title>
            <description>Those assigned to L-DOPA will begin taking 37.5mg carbidopa/150 mg levodopa once daily (with placebo twice daily) for one week, then increase to 75mg carbidopa/300mg levodopa (37.5 mg carbidopa/150mg levodopa twice daily and placebo once daily) for one week, and finally increase to 112.5mg carbidopa/450mg levodopa (37.5 mg carbidopa/150mg levodopa three times daily and no placebo) for the final six weeks. Each subject assigned to the L-DOPA arm will be titrated to 450mg L-DOPA unless they cannot tolerate higher doses, in which case subjects will have their dosage reduced to the maximum tolerable dose&#xD;
L-DOPA: We will be using generic sinemet 25/100 tablets in this study.</description>
          </group>
          <group group_id="O2">
            <title>Placebo Arm</title>
            <description>Subjects assigned to the placebo arm will take placebo oral tablet three times daily throughout the study.&#xD;
Placebo Oral Tablet: 25/100 placebo tablets</description>
          </group>
        </group_list>
        <measure>
          <title>Inventory of Depressive Symptomatology--Self Report (IDS-SR)</title>
          <description>The Inventory of Depressive Symptomatology--Self Report (IDS-SR) is a rating scale for depressive symptoms based on standard diagnostic criteria for Major Depressive Disorder. The scale ranges from 0-84 with higher scores indicating more severe depression. Because the full sample was not enrolled and the results are considered unreliable, no statistical analysis was performed other than calculating means and standard deviations.</description>
          <population>Participants with available Week 8 data 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="10"/>
                <count group_id="O2" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-9.8" spread="7.1"/>
                    <measurement group_id="O2" value="-12.1" spread="15.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Pattern Comparison Test</title>
        <description>This test required participants to identify whether two visual patterns are the &quot;same&quot; or &quot;not the same&quot; (responses were made by pressing a &quot;yes&quot; or &quot;no&quot; button). Patterns were either identical or varied on one of three dimensions: color (all ages), adding/taking something away (all ages), or one versus many. Scores reflect the number of correct items completed in 90 s, with scores ranging from a minimum of 0 to a maximum of 30. Items were designed to minimize the number of errors that were made. Because the full sample was not enrolled and the results are considered unreliable, no statistical analysis was performed other than calculating means and standard deviations.</description>
        <time_frame>Change from Baseline to 8 Weeks</time_frame>
        <population>Participants with available Week 8 data were analyzed</population>
        <group_list>
          <group group_id="O1">
            <title>L-DOPA Arm</title>
            <description>Those assigned to L-DOPA will begin taking 37.5mg carbidopa/150 mg levodopa once daily (with placebo twice daily) for one week, then increase to 75mg carbidopa/300mg levodopa (37.5 mg carbidopa/150mg levodopa twice daily and placebo once daily) for one week, and finally increase to 112.5mg carbidopa/450mg levodopa (37.5 mg carbidopa/150mg levodopa three times daily and no placebo) for the final six weeks. Each subject assigned to the L-DOPA arm will be titrated to 450mg L-DOPA unless they cannot tolerate higher doses, in which case subjects will have their dosage reduced to the maximum tolerable dose&#xD;
L-DOPA: We will be using generic sinemet 25/100 tablets in this study.</description>
          </group>
          <group group_id="O2">
            <title>Placebo Arm</title>
            <description>Subjects assigned to the placebo arm will take placebo oral tablet three times daily throughout the study.&#xD;
Placebo Oral Tablet: 25/100 placebo tablets</description>
          </group>
        </group_list>
        <measure>
          <title>Pattern Comparison Test</title>
          <description>This test required participants to identify whether two visual patterns are the &quot;same&quot; or &quot;not the same&quot; (responses were made by pressing a &quot;yes&quot; or &quot;no&quot; button). Patterns were either identical or varied on one of three dimensions: color (all ages), adding/taking something away (all ages), or one versus many. Scores reflect the number of correct items completed in 90 s, with scores ranging from a minimum of 0 to a maximum of 30. Items were designed to minimize the number of errors that were made. Because the full sample was not enrolled and the results are considered unreliable, no statistical analysis was performed other than calculating means and standard deviations.</description>
          <population>Participants with available Week 8 data were analyzed</population>
          <units>Number of items correctly completed</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="11"/>
                <count group_id="O2" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.6" spread="2.1"/>
                    <measurement group_id="O2" value="1.2" spread="2.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Letter Comparison Test</title>
        <description>Subjects were asked to determine whether two strings of letters are the same or different. There are 3 pages and the subject is given 30 seconds per page. Scoring is based on the number answered correctly. Scores range from 0 to 21, with the higher the number, the better the score. Because the full sample was not enrolled and the results are considered unreliable, no statistical analysis was performed other than calculating means and standard deviations.</description>
        <time_frame>Change from Baseline to 8 Weeks</time_frame>
        <population>Participants with available Week 8 data were analyzed</population>
        <group_list>
          <group group_id="O1">
            <title>L-DOPA Arm</title>
            <description>Those assigned to L-DOPA will begin taking 37.5mg carbidopa/150 mg levodopa once daily (with placebo twice daily) for one week, then increase to 75mg carbidopa/300mg levodopa (37.5 mg carbidopa/150mg levodopa twice daily and placebo once daily) for one week, and finally increase to 112.5mg carbidopa/450mg levodopa (37.5 mg carbidopa/150mg levodopa three times daily and no placebo) for the final six weeks. Each subject assigned to the L-DOPA arm will be titrated to 450mg L-DOPA unless they cannot tolerate higher doses, in which case subjects will have their dosage reduced to the maximum tolerable dose&#xD;
L-DOPA: We will be using generic sinemet 25/100 tablets in this study.</description>
          </group>
          <group group_id="O2">
            <title>Placebo Arm</title>
            <description>Subjects assigned to the placebo arm will take placebo oral tablet three times daily throughout the study.&#xD;
Placebo Oral Tablet: 25/100 placebo tablets</description>
          </group>
        </group_list>
        <measure>
          <title>Letter Comparison Test</title>
          <description>Subjects were asked to determine whether two strings of letters are the same or different. There are 3 pages and the subject is given 30 seconds per page. Scoring is based on the number answered correctly. Scores range from 0 to 21, with the higher the number, the better the score. Because the full sample was not enrolled and the results are considered unreliable, no statistical analysis was performed other than calculating means and standard deviations.</description>
          <population>Participants with available Week 8 data were analyzed</population>
          <units>Number of items correctly completed</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="11"/>
                <count group_id="O2" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.2" spread="1.6"/>
                    <measurement group_id="O2" value="0.7" spread="1.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Subjects were monitored over a period of 8 weeks.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>L-DOPA Arm</title>
          <description>Those assigned to L-DOPA will begin taking 37.5mg carbidopa/150 mg levodopa once daily (with placebo twice daily) for one week, then increase to 75mg carbidopa/300mg levodopa (37.5 mg carbidopa/150mg levodopa twice daily and placebo once daily) for one week, and finally increase to 112.5mg carbidopa/450mg levodopa (37.5 mg carbidopa/150mg levodopa three times daily and no placebo) for the final six weeks. Each subject assigned to the L-DOPA arm will be titrated to 450mg L-DOPA unless they cannot tolerate higher doses, in which case subjects will have their dosage reduced to the maximum tolerable dose&#xD;
L-DOPA: We will be using generic sinemet 25/100 tablets in this study.</description>
        </group>
        <group group_id="E2">
          <title>Placebo Arm</title>
          <description>Subjects assigned to the placebo arm will take placebo oral tablet three times daily throughout the study.&#xD;
Placebo Oral Tablet: 25/100 placebo tablets</description>
        </group>
      </group_list>
      <serious_events>
        <default_assessment>Systematic Assessment</default_assessment>
        <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="1" subjects_at_risk="16"/>
              </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="2" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Hospitalization for infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Death by suicide</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="16"/>
              </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="14" subjects_at_risk="15"/>
                <counts group_id="E2" subjects_affected="15" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Blurred vision</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="15"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="8" subjects_affected="5" subjects_at_risk="15"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Dry mouth</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="15"/>
                <counts group_id="E2" events="4" subjects_affected="4" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="15"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="15"/>
                <counts group_id="E2" events="3" subjects_affected="2" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Stomach/throat discomfort</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="15"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Increased appetite</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Weight loss</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Decreased appetite</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E2" events="4" subjects_affected="4" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Diverticulitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Hot flashes</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="15"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Malaise/weakness</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Poor balance</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Toe fracture</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Neck/back pain</sub_title>
                <counts group_id="E1" events="6" subjects_affected="5" subjects_at_risk="15"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Joint/limb pain</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="15"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Leg/ankle swelling</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="15"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Muscle tightness/rigidity</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Bursitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Incidental MRI finding</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="15"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="15"/>
                <counts group_id="E2" events="5" subjects_affected="5" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Numbness</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Word finding difficulty</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Anxiety during neuroimaging</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" events="7" subjects_affected="6" subjects_at_risk="15"/>
                <counts group_id="E2" events="7" subjects_affected="6" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Drowsiness</sub_title>
                <counts group_id="E1" events="6" subjects_affected="5" subjects_at_risk="15"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Excitement</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="15"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Vivid dreams</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Irritability</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Forgetfulness</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Suicidal ideation</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Panic</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Increased urination</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="15"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Cloudy urine</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Sighing</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Nasal congestion</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Hyperventilation</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Itching</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="15"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Increased sweating</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" events="6" subjects_affected="6" subjects_at_risk="15"/>
                <counts group_id="E2" events="4" subjects_affected="4" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Increased heart rate</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="15"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Decreased heart rate</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Abnormal heart rhythm</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Palpitations</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT 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>Data collected in the trial have been presented as required but are considered unreliable.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Dr. Bret Rutherford</name_or_title>
      <organization>New York State Psychiatric Institute</organization>
      <phone>646 774 8660</phone>
      <email>bret.rutherford@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/NCT03761030
org study id: 7733
secondary id: 4R33MH110029-03
nct id: NCT03761030
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
Individuals with Late Life Depression (LLD) often have cognitive problems, particularly
      problems with memory, attention, and problem solving, all of which contribute to
      antidepressant non-response. Our group and others have shown that decreased thinking speed is
      the central cause of functional problems in patients with LLD. Similarly, decreased walking
      speed is associated with depression and carries additional risk for falls, hospitalization,
      and death. Available evidence suggests that declining functionality in the brain's dopamine
      system contributes to age-related cognitive and motor slowing. The central hypothesis of this
      study is that by enhancing dopamine functioning in the brain and improving cognitive and
      motor slowing, administration of carbidopa/levodopa (L-DOPA) will improve depressive symptoms
      in older adults.
Enrolled participants were aged 60 and older with (1) a DSM 5 depressive disorder, (2)
      significant depressive symptoms, and (3) decreased thinking or walking speed will receive 8
      weeks of treatment with L-DOPA up to 450mg. We will test whether L-DOPA increases brain
      dopamine release using neuroimaging and whether it speeds up thinking and walking speed. Data
      collected in the proposed studies may help identify a new treatment for LLD, which could have
      large public health ramifications given the prevalence, frequent treatment resistance, and
      chronicity characteristic of LLD. This project also will elucidate the neurobiology of
      slowing at molecular, structural, and functional levels of analysis, increasing our
      understanding of the interplay between these aging-associated processes and the
      pathophysiologic changes underlying late life neuropsychiatric disorders. Exploring patient
      characteristics that predict response to L-DOPA may provide useful information to guide
      differential therapeutics and develop personalized medicine for LLD.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
masking description: Double Blind
measure: Change From Baseline Hamilton Rating Scale for Depression 24-Item Scale to Study Completion (8 Weeks)
time frame: Change from Baseline to 8 Weeks
description: The Hamilton Rating Scale for Depression (HRSD) is a 24-item questionnaire used as an indication of depression and a guide to evaluate recovery. Total scores range from 0-74, not including atypical symptoms sub-scale. A score of 16 or above is typically considered to indicate the presence of depressive symptoms. Higher scores indicate greater severity. Because the full sample was not enrolled and the results are considered unreliable, no statistical analysis was performed other than calculating means and standard deviations.
measure: Digit Symbol Test
time frame: Change from Baseline to 8 Weeks
description: The Digit Symbol test is a neuropsychological test measuring information processing speed. It consists of digit-symbol pairs (e.g. 1/-,2/┴ ... 7/Λ,8/X,9/=) followed by a list of digits. Under each digit the subject should write down the corresponding symbol as fast as possible. The number of correct symbols within the allowed time is measured. Score ranges from 0-133, with higher scores indicating higher information processing speed. Because the full sample was not enrolled and the results are considered unreliable, no statistical analysis was performed other than calculating means and standard deviations.
measure: Single Task Gait Speed
time frame: Change from Baseline to 8 Weeks
description: Patients' gait was assessed as walking speed in cm/s on a 15' walking course. Patients walked at their usual or normal speed for a total of 27' (starting and ending at a point 6 feet prior to and after the 15' course to eliminate acceleration and deceleration effects). Two trials were completed, and gait speed was based on the average of 2 trials. Because the full sample was not enrolled and the results are considered unreliable, no statistical analysis was performed other than calculating means and standard deviations.
measure: Inventory of Depressive Symptomatology--Self Report (IDS-SR)
time frame: Change from Baseline to 8 Weeks
description: The Inventory of Depressive Symptomatology--Self Report (IDS-SR) is a rating scale for depressive symptoms based on standard diagnostic criteria for Major Depressive Disorder. The scale ranges from 0-84 with higher scores indicating more severe depression. Because the full sample was not enrolled and the results are considered unreliable, no statistical analysis was performed other than calculating means and standard deviations.
measure: Pattern Comparison Test
time frame: Change from Baseline to 8 Weeks
description: This test required participants to identify whether two visual patterns are the "same" or "not the same" (responses were made by pressing a "yes" or "no" button). Patterns were either identical or varied on one of three dimensions: color (all ages), adding/taking something away (all ages), or one versus many. Scores reflect the number of correct items completed in 90 s, with scores ranging from a minimum of 0 to a maximum of 30. Items were designed to minimize the number of errors that were made. Because the full sample was not enrolled and the results are considered unreliable, no statistical analysis was performed other than calculating means and standard deviations.
measure: Letter Comparison Test
time frame: Change from Baseline to 8 Weeks
description: Subjects were asked to determine whether two strings of letters are the same or different. There are 3 pages and the subject is given 30 seconds per page. Scoring is based on the number answered correctly. Scores range from 0 to 21, with the higher the number, the better the score. Because the full sample was not enrolled and the results are considered unreliable, no statistical analysis was performed other than calculating means and standard deviations.
arm group label: L-DOPA Arm
arm group type: Experimental
description: Those assigned to L-DOPA will begin taking 37.5mg carbidopa/150 mg levodopa once daily (with placebo twice daily) for one week, then increase to 75mg carbidopa/300mg levodopa (37.5 mg carbidopa/150mg levodopa twice daily and placebo once daily) for one week, and finally increase to 112.5mg carbidopa/450mg levodopa (37.5 mg carbidopa/150mg levodopa three times daily and no placebo) for the final six weeks. Each subject assigned to the L-DOPA arm will be titrated to 450mg L-DOPA unless they cannot tolerate higher doses, in which case subjects will have their dosage reduced to the maximum tolerable dose
arm group label: Placebo Arm
arm group type: Placebo Comparator
description: Subjects assigned to the placebo arm will take placebo oral tablet three times daily throughout the study.
intervention type: Drug
intervention name: L-DOPA
description: We will be using generic sinemet 25/100 tablets in this study.
arm group label: L-DOPA Arm
other name: carbidopa/levodopa (Sinemet)
intervention type: Drug
intervention name: Placebo Oral Tablet
description: 25/100 placebo tablets
arm group label: Placebo Arm
other name: Placebo
criteria: 
gender: All
minimum age: 60 Years
maximum age: N/A
healthy volunteers: No
last name: Bret Rutherford, MD
role: Principal Investigator
affiliation: New York State Psychiatric Institute
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: New York State Psychiatric Institute
investigator full name: Bret Rutherford
investigator title: Associate Professor of Clinical Psychiatry
mesh term: Depression
mesh term: Depressive Disorder
mesh term: Depressive Disorder, Major
mesh term: Dysthymic Disorder
mesh term: Levodopa
mesh term: Carbidopa
mesh term: Carbidopa, levodopa drug combination
sharing ipd: No
provided document: 
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: Data collected in the trial have been presented as required but are considered unreliable.
point of contact: 