<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/NCT04493320</url>
  </required_header>
  <id_info>
    <org_study_id>7976</org_study_id>
    <secondary_id>R01MH123660-01</secondary_id>
    <nct_id>NCT04493320</nct_id>
  </id_info>
  <brief_title>1/2-Dopaminergic Dysfunction in Late-Life Depression (The D3 Study)</brief_title>
  <official_title>1/2-Dopaminergic Dysfunction in Late-Life Depression (The D3 Study)</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>
    <collaborator>
      <agency>Vanderbilt University Medical Center</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Columbia University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Emory University</agency>
      <agency_class>Other</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>
  </oversight_info>
  <brief_summary>
    <textblock>
      Growing evidence suggests that dopamine contributes to key cognitive, emotional, and motor&#xD;
      functions across the lifespan. In Late-Life Depression (LLD), dysfunction in these areas is&#xD;
      common, predicts poor outcomes, and manifests as difficulties in motivation and effort along&#xD;
      with cognitive and gait impairment. While studies of dopamine function in early and midlife&#xD;
      depression primarily focus on individuals' ability to feel pleasure and respond to rewards,&#xD;
      they often exclude the cognitive and physical function domains relevant for older adults&#xD;
      despite a recognized decline in dopamine function with normal aging. The objectives of this&#xD;
      collaborative R01 proposal between Columbia University/New York State Psychiatric Institute&#xD;
      and Vanderbilt University Medical Center are to: 1) characterize dopaminergic dysfunction in&#xD;
      LLD across cognitive, emotional, and motor domains at several levels of analysis (cellular&#xD;
      Positron Emission Tomography [PET], circuit Magnetic Resonance Imaging [MRI], and behavioral&#xD;
      / self-report); and 2) examine the responsivity of dopamine-related circuits and behavior to&#xD;
      stimulation with carbidopa/levodopa (L-DOPA).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Supported by pilot data, this project builds on past work demonstrating that dopamine&#xD;
      function declines with aging, that dopaminergic dysfunction contributes to deficits in&#xD;
      behavior, and that L-DOPA administration improves cognitive and motor performance. The&#xD;
      long-term goal of this line of research is to determine how dopaminergic dysfunction&#xD;
      contributes to clinical presentations of LLD, how responsive behavioral symptoms are to&#xD;
      modulation of dopamine function, and to identify novel targets for future interventions.&#xD;
      Investigator's approach is to enroll 30 psychiatrically healthy elders and 60 depressed&#xD;
      elders at Columbia/NYSPI exhibiting either slowed processing speed or slowed gait speed.&#xD;
      Participants will undergo thorough clinical evaluations and complete PET imaging measuring&#xD;
      different aspects of the brain's dopamine system, neuromelanin-sensitive MRI measurement of&#xD;
      longterm dopamine transmission, functional MRI focused on effort-based decision making and&#xD;
      reward processing, a comprehensive neurocognitive evaluation, a physical performance&#xD;
      evaluation, and measurement of inflammatory markers. To assess responsivity of the dopamine&#xD;
      system to modulation, depressed subjects then will be randomized to L-DOPA or placebo for 3&#xD;
      weeks, followed by repeat multimodal MRI and cognitive/behavioral assessments. In a second&#xD;
      phase, participants will receive the opposite intervention for an additional 3 weeks followed&#xD;
      by clinical and cognitive assessments only. This proposal is significant and innovative, as&#xD;
      no prior published study has comprehensively examined dopamine-dependent behaviors in LLD.&#xD;
      This will inform treatment approaches focusing on facilitating cognition and movement,&#xD;
      reducing the effort cost of voluntary behavior, and promoting behavioral activation.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Study terminated by sponsor (NIMH)&#xD;
  </why_stopped>
  <start_date type="Actual">February 10, 2021</start_date>
  <completion_date type="Actual">October 27, 2021</completion_date>
  <primary_completion_date type="Actual">October 27, 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>Crossover Assignment</intervention_model>
    <intervention_model_description>Double blind crossover study</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in Effort Expenditure for Rewards Task (EEfRT) Following Step 1</measure>
    <time_frame>Change from Baseline to 3 weeks (post Step 1)</time_frame>
    <description>In this task participants decide whether to work harder for a larger reward (high number of finger presses with their pinky) or expend less energy (low number of presses with a dominant index finger) for a lesser reward, with lower rewards being $1 dollar and higher rewards ranging from $1.20 to $5. Participants receive information about the probability of winning on each trial regardless of their pick and one trial from each run is randomly picked for payout. The primary output on this task is the percentage of time participants choose the high cost / high reward option on the EEfRT. 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.&#xD;
This task was not completed following Step 2 of the study, so there are no EEfRT data reported for change in task performance following Step 2.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in Digit Symbol Test Following Step 1</measure>
    <time_frame>Change from Baseline to 3 weeks (post Step 1)</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>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in Digit Symbol Test Following Step 2</measure>
    <time_frame>Change from Week 3 to Week 7 (post-Step 2)</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>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in Pattern Comparison Test Following Step 1</measure>
    <time_frame>Change from Baseline to 3 weeks (post Step 1)</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>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in Pattern Comparison Test Following Step 2</measure>
    <time_frame>Change from Week 3 to Week 7 (post-Step 2)</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>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in Letter Comparison Test Following Step 1</measure>
    <time_frame>Change from Baseline to 3 weeks (post Step 1)</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>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in Letter Comparison Test Following Step 2</measure>
    <time_frame>Change from Week 3 to Week 7 (post-Step 2)</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>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in Single Task Gait Speed Test Following Step 1</measure>
    <time_frame>Change from Baseline to 3 weeks (post Step 1)</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>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in Single Task Gait Speed Test Following Step 2</measure>
    <time_frame>Change from Week 3 to Week 7 (post-Step 2)</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>
  </primary_outcome>
  <primary_outcome>
    <measure>[18F]-FDOPA PET Measure in Striatal Region of Interest</measure>
    <time_frame>Baseline (prior to LDOPA or placebo administration)</time_frame>
    <description>[18F]-FDOPA PET quantifies dopamine synthesis capacity in specific brain regions. Lower [18F]-FDOPA uptake in the striatum has been associated with increased depression severity and worse cognitive and motor function in patients. Because [18F]-FDOPA uptake may be sensitive to deficits in dopamine synthesis capacity in older depressed patients, in this study depressed participants at baseline underwent a PET scan to quantify relative [18F]-FDOPA influx rate in the nucleus accumbens bilaterally. Time activity curves (TACs) were extracted within the nucleus accumbens region of interest (ROI) as the average radioactivity in the ROI over time. The occipital lobe, which has the lowest dopamine concentration in the brain, was used as the &quot;reference region&quot; to yield the Kocc measure of [18F]-FDOPA influx rate. Higher [18F]-FDOPA influx rate (kocc) numbers indicate greater relative influx rate and therefore greater dopamine synthesis capacity.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in Montgomery Asberg Depression Rating Scale Following Step 1</measure>
    <time_frame>Change from Baseline to 3 weeks (post Step 1)</time_frame>
    <description>Secondary outcome measured by the total score of the clinician rated MADRS, a measure of depression severity. The MADRS total score range is 0-60, where higher scores indicate greater depression 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>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Montgomery Asberg Depression Rating Scale Following Step 2</measure>
    <time_frame>Change from Week 4 to Week 7 (post-Step 2)</time_frame>
    <description>Secondary outcome measured by the total score of the clinician rated MADRS, a measure of depression severity. The MADRS total score range is 0-60, where higher scores indicate greater depression severity. In contrast to other measures, which were not available at Week 4, Week 4 was selected as the baseline for post-Step 2 change on the MADRS since it followed the taper period taking place between study Steps. 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>Change in Quick Inventory for Depressive Symptomatology (QIDS) Following Step 1</measure>
    <time_frame>Change from Baseline to 3 weeks (post Step 1)</time_frame>
    <description>QIDS-16-item, a participant-rated measure of depressive symptomatology. The total score ranges from 0 to 27, with higher scores indicative of 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>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Quick Inventory for Depressive Symptomatology (QIDS) Following Step 2</measure>
    <time_frame>Change from Week 4 to Week 7 (post-Step 2)</time_frame>
    <description>QIDS-16-item, a participant-rated measure of depressive symptomatology. The total score ranges from 0 to 27, with higher scores indicative of greater severity. In contrast to other measures, which were not available at Week 4, Week 4 was selected as the baseline for post-Step 2 change on the QIDS since it followed the taper period taking place between study Steps. 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">5</enrollment>
  <condition>Depression</condition>
  <condition>Cognitive Impairment</condition>
  <condition>Gait Impairment</condition>
  <arm_group>
    <arm_group_label>L-DOPA, Then Placebo</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Step 1 (3 Weeks): Participants will first receive 150 mg of L-DOPA daily in Week 1, 300 mg of L-DOPA in Week 2, and 450 mg L-DOPA in Week 3.&#xD;
Participants will then enter a 1 week taper period.&#xD;
Step 2 (3 Weeks): Participants will receive L-DOPA matching placebo tablets daily.&#xD;
Participants will then enter a 1-week taper period.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo, Then L-DOPA</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Step 1 (3 Weeks): Participants will receive 3 L-DOPA matching placebo tablets daily. Participants will then enter a 1-week taper period.&#xD;
Step 2 (3 Weeks): Participants will first receive 150 mg of L-DOPA daily in Week 1, 300 mg of L-DOPA in Week 2, and 450 mg L-DOPA in Week 3.&#xD;
Participants will then enter a 1-week taper period.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Carbidopa/levodopa</intervention_name>
    <description>150-450mg carbidopa/levodopa 3 times daily</description>
    <arm_group_label>L-DOPA, Then Placebo</arm_group_label>
    <arm_group_label>Placebo, Then L-DOPA</arm_group_label>
    <other_name>L-DOPA</other_name>
    <other_name>Sinemet</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Carbidopa/levodopa-matched placebo tablet 3 times daily</description>
    <arm_group_label>L-DOPA, Then Placebo</arm_group_label>
    <arm_group_label>Placebo, Then L-DOPA</arm_group_label>
    <other_name>Placebo tablet</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Depressed Subjects:&#xD;
&#xD;
          1. Age 60 years or older (female subjects will be post-menopausal by virtue of their age,&#xD;
             but last menstrual period month and year will be documented in the study database)&#xD;
&#xD;
          2. Diagnosis and Statistical Manual (DSM-5) diagnosis of Major Depressive Disorder (MDD)&#xD;
             or Persistent Depressive Disorder (PDD)&#xD;
&#xD;
          3. Montgomery Asberg Depression Rating Scale Score (MADRS) &gt;=15&#xD;
&#xD;
          4. Decreased processing speed or decreased gait speed&#xD;
&#xD;
          5. Capable of providing informed consent and complying with study procedures&#xD;
&#xD;
          6. Alternative standard treatments for MDD or PDD have been discussed and the individual&#xD;
             agrees to be involved in an experimental treatment&#xD;
&#xD;
        Psychiatrically Healthy Elders:&#xD;
&#xD;
          1. Age 60 years or older years old&#xD;
&#xD;
          2. MADRS &lt; 8&#xD;
&#xD;
          3. Capable of providing informed consent and complying with study procedures&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Depressed Subjects:&#xD;
&#xD;
          1. Diagnosis of Substance Use Disorder (excluding Tobacco Use Disorder) in the past 12&#xD;
             months&#xD;
&#xD;
          2. History of psychosis (except brief psychosis associated with transient medical&#xD;
             conditions [e.g., delirium, urinary tract infection, etc], psychotic disorder, mania,&#xD;
             or bipolar disorder.&#xD;
&#xD;
          3. Primary neurological disorder, including dementia, stroke, Parkinson's disease, or&#xD;
             epilepsy.&#xD;
&#xD;
          4. Mini Mental State Examination (MMSE) &lt; 24&#xD;
&#xD;
          5. MADRS suicide item &gt;4 or other indication of acute suicidality&#xD;
&#xD;
          6. Current or recent (within the past 2 weeks) treatment with antidepressants,&#xD;
             antipsychotics, or mood stabilizers&#xD;
&#xD;
          7. History of hypersensitivity, allergy, or intolerance to L-DOPA&#xD;
&#xD;
          8. Any physical or intellectual disability adversely affecting ability to complete&#xD;
             assessments.&#xD;
&#xD;
          9. Acute, severe, or unstable medical illness&#xD;
&#xD;
         10. Mobility limiting osteoarthritis of any lower extremity joints, symptomatic lumbar&#xD;
             spine disease, or history of joint replacement or spine surgery that limits mobility&#xD;
&#xD;
         11. Contraindication to MRI scanning (Metal implants, pacemaker, metal prostheses, metal&#xD;
             orthodontic appliances in the body unless there is confirmation that the substance is&#xD;
             MRI compatible.)&#xD;
&#xD;
         12. History of significant radioactivity exposure (nuclear medicine studies or&#xD;
             occupational exposure)&#xD;
&#xD;
         13. Has a medical condition managed with medication and/or device and the managing&#xD;
             physician considers the condition and/or its management a contraindication to the&#xD;
             research use of L-DOPA in this participant&#xD;
&#xD;
        Psychiatrically Healthy Elders:&#xD;
&#xD;
          1. Any personal history of DSM-5 disorder&#xD;
&#xD;
          2. Family history of MDD in first-degree relative&#xD;
&#xD;
          3. Plus, Exclusion criteria 8-12 above&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>60 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Bret R 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>July 27, 2020</study_first_submitted>
  <study_first_submitted_qc>July 27, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 30, 2020</study_first_posted>
  <results_first_submitted>May 9, 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>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Depression</mesh_term>
    <mesh_term>Depressive 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>July 24, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/20/NCT04493320/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>October 3, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/20/NCT04493320/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>July 24, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/20/NCT04493320/ICF_002.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>In total, 5 depressed subjects were enrolled. Of the 5 enrolled, 1 subject was found to be ineligible. Thus, 5 participants enrolled and 4 were assigned to a treatment group and began the study.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>L-DOPA, Then Placebo</title>
          <description>Step 1 (3 Weeks): Participants will first receive 150 mg of L-DOPA daily in Week 1, 300 mg of L-DOPA in Week 2, and 450 mg L-DOPA in Week 3.&#xD;
Participants will then enter a 1 week taper period.&#xD;
Step 2 (3 Weeks): Participants will receive L-DOPA matching placebo tablets daily.&#xD;
Participants will then enter a 1-week taper period.&#xD;
Carbidopa/levodopa: 150-450mg carbidopa/levodopa 3 times daily&#xD;
Placebo: Carbidopa/levodopa-matched placebo tablet 3 times daily</description>
        </group>
        <group group_id="P2">
          <title>Placebo, Then L-DOPA</title>
          <description>Step 1 (3 Weeks): Participants will receive 3 L-DOPA matching placebo tablets daily. Participants will then enter a 1-week taper period.&#xD;
Step 2 (3 Weeks): Participants will first receive 150 mg of L-DOPA daily in Week 1, 300 mg of L-DOPA in Week 2, and 450 mg L-DOPA in Week 3.&#xD;
Participants will then enter a 1-week taper period.&#xD;
Carbidopa/levodopa: 150-450mg carbidopa/levodopa 3 times daily&#xD;
Placebo: Carbidopa/levodopa-matched placebo tablet 3 times daily</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>L-DOPA, Then Placebo</title>
          <description>Step 1 (3 Weeks): Participants will first receive 150 mg of L-DOPA daily in Week 1, 300 mg of L-DOPA in Week 2, and 450 mg L-DOPA in Week 3.&#xD;
Participants will then enter a 1 week taper period.&#xD;
Step 2 (3 Weeks): Participants will receive L-DOPA matching placebo tablets daily.&#xD;
Participants will then enter a 1-week taper period.&#xD;
Carbidopa/levodopa: 150-450mg carbidopa/levodopa 3 times daily&#xD;
Placebo: Carbidopa/levodopa-matched placebo tablet 3 times daily</description>
        </group>
        <group group_id="B2">
          <title>Placebo, Then L-DOPA</title>
          <description>Step 1 (3 Weeks): Participants will receive 3 L-DOPA matching placebo tablets daily. Participants will then enter a 1-week taper period.&#xD;
Step 2 (3 Weeks): Participants will first receive 150 mg of L-DOPA daily in Week 1, 300 mg of L-DOPA in Week 2, and 450 mg L-DOPA in Week 3.&#xD;
Participants will then enter a 1-week taper period.&#xD;
Carbidopa/levodopa: 150-450mg carbidopa/levodopa 3 times daily&#xD;
Placebo: Carbidopa/levodopa-matched placebo tablet 3 times daily</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="2"/>
            <count group_id="B2" value="2"/>
            <count group_id="B3" value="4"/>
          </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="74.5" spread="16.3"/>
                    <measurement group_id="B2" value="65.5" spread="7.8"/>
                    <measurement group_id="B3" value="70.0" spread="11.6"/>
                  </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 group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="3"/>
                  </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 group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</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>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="0"/>
                    <measurement group_id="B3" value="0"/>
                  </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="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</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>More than one race</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>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>Montgomery Asberg Depression Rating Scale</title>
          <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="24.5" spread="5.0"/>
                    <measurement group_id="B2" value="36.5" spread="12.0"/>
                    <measurement group_id="B3" value="25.5" spread="7.6"/>
                  </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="5.0" spread="0.0"/>
                    <measurement group_id="B2" value="4.0" spread="0.0"/>
                    <measurement group_id="B3" value="4.3" spread="0.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Quick Inventory for Depressive Symptomatology</title>
          <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="10.0" spread="0.0"/>
                    <measurement group_id="B2" value="15.0" spread="4.2"/>
                    <measurement group_id="B3" value="13.3" spread="4.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change in Effort Expenditure for Rewards Task (EEfRT) Following Step 1</title>
        <description>In this task participants decide whether to work harder for a larger reward (high number of finger presses with their pinky) or expend less energy (low number of presses with a dominant index finger) for a lesser reward, with lower rewards being $1 dollar and higher rewards ranging from $1.20 to $5. Participants receive information about the probability of winning on each trial regardless of their pick and one trial from each run is randomly picked for payout. The primary output on this task is the percentage of time participants choose the high cost / high reward option on the EEfRT. 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.&#xD;
This task was not completed following Step 2 of the study, so there are no EEfRT data reported for change in task performance following Step 2.</description>
        <time_frame>Change from Baseline to 3 weeks (post Step 1)</time_frame>
        <population>Participants with Baseline and Week 3 data available were analyzed</population>
        <group_list>
          <group group_id="O1">
            <title>L-DOPA, Then Placebo</title>
            <description>Step 1 (3 Weeks): Participants will first receive 150 mg of L-DOPA daily in Week 1, 300 mg of L-DOPA in Week 2, and 450 mg L-DOPA in Week 3.&#xD;
Participants will then enter a 1 week taper period.&#xD;
Step 2 (3 Weeks): Participants will receive L-DOPA matching placebo tablets daily.&#xD;
Participants will then enter a 1-week taper period.&#xD;
Carbidopa/levodopa: 150-450mg carbidopa/levodopa 3 times daily&#xD;
Placebo: Carbidopa/levodopa-matched placebo tablet 3 times daily</description>
          </group>
          <group group_id="O2">
            <title>Placebo, Then L-DOPA</title>
            <description>Step 1 (3 Weeks): Participants will receive 3 L-DOPA matching placebo tablets daily. Participants will then enter a 1-week taper period.&#xD;
Step 2 (3 Weeks): Participants will first receive 150 mg of L-DOPA daily in Week 1, 300 mg of L-DOPA in Week 2, and 450 mg L-DOPA in Week 3.&#xD;
Participants will then enter a 1-week taper period.&#xD;
Carbidopa/levodopa: 150-450mg carbidopa/levodopa 3 times daily&#xD;
Placebo: Carbidopa/levodopa-matched placebo tablet 3 times daily</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Effort Expenditure for Rewards Task (EEfRT) Following Step 1</title>
          <description>In this task participants decide whether to work harder for a larger reward (high number of finger presses with their pinky) or expend less energy (low number of presses with a dominant index finger) for a lesser reward, with lower rewards being $1 dollar and higher rewards ranging from $1.20 to $5. Participants receive information about the probability of winning on each trial regardless of their pick and one trial from each run is randomly picked for payout. The primary output on this task is the percentage of time participants choose the high cost / high reward option on the EEfRT. 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.&#xD;
This task was not completed following Step 2 of the study, so there are no EEfRT data reported for change in task performance following Step 2.</description>
          <population>Participants with Baseline and Week 3 data available were analyzed</population>
          <units>percentage of high effort choices</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="1"/>
                <count group_id="O2" value="2"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.18" spread="NA">Standard Deviation is not calculable for 1 participant.</measurement>
                    <measurement group_id="O2" value="0.0" spread="0.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Change in Digit Symbol Test Following Step 1</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 3 weeks (post Step 1)</time_frame>
        <population>Participants with Baseline and Week 3 data available were analyzed</population>
        <group_list>
          <group group_id="O1">
            <title>L-DOPA, Then Placebo</title>
            <description>Step 1 (3 Weeks): Participants will first receive 150 mg of L-DOPA daily in Week 1, 300 mg of L-DOPA in Week 2, and 450 mg L-DOPA in Week 3.&#xD;
Participants will then enter a 1 week taper period.&#xD;
Step 2 (3 Weeks): Participants will receive L-DOPA matching placebo tablets daily.&#xD;
Participants will then enter a 1-week taper period.&#xD;
Carbidopa/levodopa: 150-450mg carbidopa/levodopa 3 times daily&#xD;
Placebo: Carbidopa/levodopa-matched placebo tablet 3 times daily</description>
          </group>
          <group group_id="O2">
            <title>Placebo, Then L-DOPA</title>
            <description>Step 1 (3 Weeks): Participants will receive 3 L-DOPA matching placebo tablets daily. Participants will then enter a 1-week taper period.&#xD;
Step 2 (3 Weeks): Participants will first receive 150 mg of L-DOPA daily in Week 1, 300 mg of L-DOPA in Week 2, and 450 mg L-DOPA in Week 3.&#xD;
Participants will then enter a 1-week taper period.&#xD;
Carbidopa/levodopa: 150-450mg carbidopa/levodopa 3 times daily&#xD;
Placebo: Carbidopa/levodopa-matched placebo tablet 3 times daily</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Digit Symbol Test Following Step 1</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 Baseline and Week 3 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="2"/>
                <count group_id="O2" value="2"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.5" spread="2.1"/>
                    <measurement group_id="O2" value="9.0" spread="7.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Change in Digit Symbol Test Following Step 2</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 Week 3 to Week 7 (post-Step 2)</time_frame>
        <population>Participants with Week 3 and Week 7 data available were analyzed</population>
        <group_list>
          <group group_id="O1">
            <title>L-DOPA, Then Placebo</title>
            <description>Step 1 (3 Weeks): Participants will first receive 150 mg of L-DOPA daily in Week 1, 300 mg of L-DOPA in Week 2, and 450 mg L-DOPA in Week 3.&#xD;
Participants will then enter a 1 week taper period.&#xD;
Step 2 (3 Weeks): Participants will receive L-DOPA matching placebo tablets daily.&#xD;
Participants will then enter a 1-week taper period.&#xD;
Carbidopa/levodopa: 150-450mg carbidopa/levodopa 3 times daily&#xD;
Placebo: Carbidopa/levodopa-matched placebo tablet 3 times daily</description>
          </group>
          <group group_id="O2">
            <title>Placebo, Then L-DOPA</title>
            <description>Step 1 (3 Weeks): Participants will receive 3 L-DOPA matching placebo tablets daily. Participants will then enter a 1-week taper period.&#xD;
Step 2 (3 Weeks): Participants will first receive 150 mg of L-DOPA daily in Week 1, 300 mg of L-DOPA in Week 2, and 450 mg L-DOPA in Week 3.&#xD;
Participants will then enter a 1-week taper period.&#xD;
Carbidopa/levodopa: 150-450mg carbidopa/levodopa 3 times daily&#xD;
Placebo: Carbidopa/levodopa-matched placebo tablet 3 times daily</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Digit Symbol Test Following Step 2</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 3 and Week 7 data available were analyzed</population>
          <units>Number of items correctly completed</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="1"/>
                <count group_id="O2" value="1"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.0"/>
                    <measurement group_id="O2" value="4.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Change in Pattern Comparison Test Following Step 1</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 3 weeks (post Step 1)</time_frame>
        <population>Participants with Baseline and Week 3 data available were analyzed</population>
        <group_list>
          <group group_id="O1">
            <title>L-DOPA, Then Placebo</title>
            <description>Step 1 (3 Weeks): Participants will first receive 150 mg of L-DOPA daily in Week 1, 300 mg of L-DOPA in Week 2, and 450 mg L-DOPA in Week 3.&#xD;
Participants will then enter a 1 week taper period.&#xD;
Step 2 (3 Weeks): Participants will receive L-DOPA matching placebo tablets daily.&#xD;
Participants will then enter a 1-week taper period.&#xD;
Carbidopa/levodopa: 150-450mg carbidopa/levodopa 3 times daily&#xD;
Placebo: Carbidopa/levodopa-matched placebo tablet 3 times daily</description>
          </group>
          <group group_id="O2">
            <title>Placebo, Then L-DOPA</title>
            <description>Step 1 (3 Weeks): Participants will receive 3 L-DOPA matching placebo tablets daily. Participants will then enter a 1-week taper period.&#xD;
Step 2 (3 Weeks): Participants will first receive 150 mg of L-DOPA daily in Week 1, 300 mg of L-DOPA in Week 2, and 450 mg L-DOPA in Week 3.&#xD;
Participants will then enter a 1-week taper period.&#xD;
Carbidopa/levodopa: 150-450mg carbidopa/levodopa 3 times daily&#xD;
Placebo: Carbidopa/levodopa-matched placebo tablet 3 times daily</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Pattern Comparison Test Following Step 1</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 Baseline and Week 3 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="2"/>
                <count group_id="O2" value="2"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.0" spread="1.4"/>
                    <measurement group_id="O2" value="1.75" spread="1.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Change in Pattern Comparison Test Following Step 2</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 Week 3 to Week 7 (post-Step 2)</time_frame>
        <population>Participants with Week 3 and Week 7 data available were analyzed</population>
        <group_list>
          <group group_id="O1">
            <title>L-DOPA, Then Placebo</title>
            <description>Step 1 (3 Weeks): Participants will first receive 150 mg of L-DOPA daily in Week 1, 300 mg of L-DOPA in Week 2, and 450 mg L-DOPA in Week 3.&#xD;
Participants will then enter a 1 week taper period.&#xD;
Step 2 (3 Weeks): Participants will receive L-DOPA matching placebo tablets daily.&#xD;
Participants will then enter a 1-week taper period.&#xD;
Carbidopa/levodopa: 150-450mg carbidopa/levodopa 3 times daily&#xD;
Placebo: Carbidopa/levodopa-matched placebo tablet 3 times daily</description>
          </group>
          <group group_id="O2">
            <title>Placebo, Then L-DOPA</title>
            <description>Step 1 (3 Weeks): Participants will receive 3 L-DOPA matching placebo tablets daily. Participants will then enter a 1-week taper period.&#xD;
Step 2 (3 Weeks): Participants will first receive 150 mg of L-DOPA daily in Week 1, 300 mg of L-DOPA in Week 2, and 450 mg L-DOPA in Week 3.&#xD;
Participants will then enter a 1-week taper period.&#xD;
Carbidopa/levodopa: 150-450mg carbidopa/levodopa 3 times daily&#xD;
Placebo: Carbidopa/levodopa-matched placebo tablet 3 times daily</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Pattern Comparison Test Following Step 2</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 Week 3 and Week 7 data available were analyzed</population>
          <units>Number of items correctly completed</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="1"/>
                <count group_id="O2" value="1"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.0"/>
                    <measurement group_id="O2" value="-3.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Change in Letter Comparison Test Following Step 1</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 3 weeks (post Step 1)</time_frame>
        <population>Participants with Baseline and Week 3 data available were analyzed</population>
        <group_list>
          <group group_id="O1">
            <title>L-DOPA, Then Placebo</title>
            <description>Step 1 (3 Weeks): Participants will first receive 150 mg of L-DOPA daily in Week 1, 300 mg of L-DOPA in Week 2, and 450 mg L-DOPA in Week 3.&#xD;
Participants will then enter a 1 week taper period.&#xD;
Step 2 (3 Weeks): Participants will receive L-DOPA matching placebo tablets daily.&#xD;
Participants will then enter a 1-week taper period.&#xD;
Carbidopa/levodopa: 150-450mg carbidopa/levodopa 3 times daily&#xD;
Placebo: Carbidopa/levodopa-matched placebo tablet 3 times daily</description>
          </group>
          <group group_id="O2">
            <title>Placebo, Then L-DOPA</title>
            <description>Step 1 (3 Weeks): Participants will receive 3 L-DOPA matching placebo tablets daily. Participants will then enter a 1-week taper period.&#xD;
Step 2 (3 Weeks): Participants will first receive 150 mg of L-DOPA daily in Week 1, 300 mg of L-DOPA in Week 2, and 450 mg L-DOPA in Week 3.&#xD;
Participants will then enter a 1-week taper period.&#xD;
Carbidopa/levodopa: 150-450mg carbidopa/levodopa 3 times daily&#xD;
Placebo: Carbidopa/levodopa-matched placebo tablet 3 times daily</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Letter Comparison Test Following Step 1</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 Baseline and Week 3 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="2"/>
                <count group_id="O2" value="2"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.5" spread="0.0"/>
                    <measurement group_id="O2" value="-0.25" spread="2.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Change in Letter Comparison Test Following Step 2</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 Week 3 to Week 7 (post-Step 2)</time_frame>
        <population>Participants with Week 3 and Week 7 data available were analyzed</population>
        <group_list>
          <group group_id="O1">
            <title>L-DOPA, Then Placebo</title>
            <description>Step 1 (3 Weeks): Participants will first receive 150 mg of L-DOPA daily in Week 1, 300 mg of L-DOPA in Week 2, and 450 mg L-DOPA in Week 3.&#xD;
Participants will then enter a 1 week taper period.&#xD;
Step 2 (3 Weeks): Participants will receive L-DOPA matching placebo tablets daily.&#xD;
Participants will then enter a 1-week taper period.&#xD;
Carbidopa/levodopa: 150-450mg carbidopa/levodopa 3 times daily&#xD;
Placebo: Carbidopa/levodopa-matched placebo tablet 3 times daily</description>
          </group>
          <group group_id="O2">
            <title>Placebo, Then L-DOPA</title>
            <description>Step 1 (3 Weeks): Participants will receive 3 L-DOPA matching placebo tablets daily. Participants will then enter a 1-week taper period.&#xD;
Step 2 (3 Weeks): Participants will first receive 150 mg of L-DOPA daily in Week 1, 300 mg of L-DOPA in Week 2, and 450 mg L-DOPA in Week 3.&#xD;
Participants will then enter a 1-week taper period.&#xD;
Carbidopa/levodopa: 150-450mg carbidopa/levodopa 3 times daily&#xD;
Placebo: Carbidopa/levodopa-matched placebo tablet 3 times daily</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Letter Comparison Test Following Step 2</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 Week 3 and Week 7 data available were analyzed</population>
          <units>Number of items correctly completed</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="1"/>
                <count group_id="O2" value="1"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.5"/>
                    <measurement group_id="O2" value="-1.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Change in Single Task Gait Speed Test Following Step 1</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 3 weeks (post Step 1)</time_frame>
        <population>Participants with Baseline and Week 3 data available were analyzed</population>
        <group_list>
          <group group_id="O1">
            <title>L-DOPA, Then Placebo</title>
            <description>Step 1 (3 Weeks): Participants will first receive 150 mg of L-DOPA daily in Week 1, 300 mg of L-DOPA in Week 2, and 450 mg L-DOPA in Week 3.&#xD;
Participants will then enter a 1 week taper period.&#xD;
Step 2 (3 Weeks): Participants will receive L-DOPA matching placebo tablets daily.&#xD;
Participants will then enter a 1-week taper period.&#xD;
Carbidopa/levodopa: 150-450mg carbidopa/levodopa 3 times daily&#xD;
Placebo: Carbidopa/levodopa-matched placebo tablet 3 times daily</description>
          </group>
          <group group_id="O2">
            <title>Placebo, Then L-DOPA</title>
            <description>Step 1 (3 Weeks): Participants will receive 3 L-DOPA matching placebo tablets daily. Participants will then enter a 1-week taper period.&#xD;
Step 2 (3 Weeks): Participants will first receive 150 mg of L-DOPA daily in Week 1, 300 mg of L-DOPA in Week 2, and 450 mg L-DOPA in Week 3.&#xD;
Participants will then enter a 1-week taper period.&#xD;
Carbidopa/levodopa: 150-450mg carbidopa/levodopa 3 times daily&#xD;
Placebo: Carbidopa/levodopa-matched placebo tablet 3 times daily</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Single Task Gait Speed Test Following Step 1</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 Baseline and Week 3 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="2"/>
                <count group_id="O2" value="2"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.6" spread="5.9"/>
                    <measurement group_id="O2" value="11.9" spread="11.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Change in Single Task Gait Speed Test Following Step 2</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 Week 3 to Week 7 (post-Step 2)</time_frame>
        <population>Participants with Week 3 and Week 7 data available were analyzed</population>
        <group_list>
          <group group_id="O1">
            <title>L-DOPA, Then Placebo</title>
            <description>Step 1 (3 Weeks): Participants will first receive 150 mg of L-DOPA daily in Week 1, 300 mg of L-DOPA in Week 2, and 450 mg L-DOPA in Week 3.&#xD;
Participants will then enter a 1 week taper period.&#xD;
Step 2 (3 Weeks): Participants will receive L-DOPA matching placebo tablets daily.&#xD;
Participants will then enter a 1-week taper period.&#xD;
Carbidopa/levodopa: 150-450mg carbidopa/levodopa 3 times daily&#xD;
Placebo: Carbidopa/levodopa-matched placebo tablet 3 times daily</description>
          </group>
          <group group_id="O2">
            <title>Placebo, Then L-DOPA</title>
            <description>Step 1 (3 Weeks): Participants will receive 3 L-DOPA matching placebo tablets daily. Participants will then enter a 1-week taper period.&#xD;
Step 2 (3 Weeks): Participants will first receive 150 mg of L-DOPA daily in Week 1, 300 mg of L-DOPA in Week 2, and 450 mg L-DOPA in Week 3.&#xD;
Participants will then enter a 1-week taper period.&#xD;
Carbidopa/levodopa: 150-450mg carbidopa/levodopa 3 times daily&#xD;
Placebo: Carbidopa/levodopa-matched placebo tablet 3 times daily</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Single Task Gait Speed Test Following Step 2</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 3 and Week 7 data available were analyzed</population>
          <units>cm/s</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="1"/>
                <count group_id="O2" value="1"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-17.2"/>
                    <measurement group_id="O2" value="7.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>[18F]-FDOPA PET Measure in Striatal Region of Interest</title>
        <description>[18F]-FDOPA PET quantifies dopamine synthesis capacity in specific brain regions. Lower [18F]-FDOPA uptake in the striatum has been associated with increased depression severity and worse cognitive and motor function in patients. Because [18F]-FDOPA uptake may be sensitive to deficits in dopamine synthesis capacity in older depressed patients, in this study depressed participants at baseline underwent a PET scan to quantify relative [18F]-FDOPA influx rate in the nucleus accumbens bilaterally. Time activity curves (TACs) were extracted within the nucleus accumbens region of interest (ROI) as the average radioactivity in the ROI over time. The occipital lobe, which has the lowest dopamine concentration in the brain, was used as the &quot;reference region&quot; to yield the Kocc measure of [18F]-FDOPA influx rate. Higher [18F]-FDOPA influx rate (kocc) numbers indicate greater relative influx rate and therefore greater dopamine synthesis capacity.</description>
        <time_frame>Baseline (prior to LDOPA or placebo administration)</time_frame>
        <population>Participants who had a baseline [18F]-FDOPA PET scan</population>
        <group_list>
          <group group_id="O1">
            <title>L-DOPA, Then Placebo</title>
            <description>Step 1 (3 Weeks): Participants will first receive 150 mg of L-DOPA daily in Week 1, 300 mg of L-DOPA in Week 2, and 450 mg L-DOPA in Week 3.&#xD;
Participants will then enter a 1 week taper period.&#xD;
Step 2 (3 Weeks): Participants will receive L-DOPA matching placebo tablets daily.&#xD;
Participants will then enter a 1-week taper period.&#xD;
Carbidopa/levodopa: 150-450mg carbidopa/levodopa 3 times daily&#xD;
Placebo: Carbidopa/levodopa-matched placebo tablet 3 times daily</description>
          </group>
          <group group_id="O2">
            <title>Placebo, Then L-DOPA</title>
            <description>Step 1 (3 Weeks): Participants will receive 3 L-DOPA matching placebo tablets daily. Participants will then enter a 1-week taper period.&#xD;
Step 2 (3 Weeks): Participants will first receive 150 mg of L-DOPA daily in Week 1, 300 mg of L-DOPA in Week 2, and 450 mg L-DOPA in Week 3.&#xD;
Participants will then enter a 1-week taper period.&#xD;
Carbidopa/levodopa: 150-450mg carbidopa/levodopa 3 times daily&#xD;
Placebo: Carbidopa/levodopa-matched placebo tablet 3 times daily</description>
          </group>
        </group_list>
        <measure>
          <title>[18F]-FDOPA PET Measure in Striatal Region of Interest</title>
          <description>[18F]-FDOPA PET quantifies dopamine synthesis capacity in specific brain regions. Lower [18F]-FDOPA uptake in the striatum has been associated with increased depression severity and worse cognitive and motor function in patients. Because [18F]-FDOPA uptake may be sensitive to deficits in dopamine synthesis capacity in older depressed patients, in this study depressed participants at baseline underwent a PET scan to quantify relative [18F]-FDOPA influx rate in the nucleus accumbens bilaterally. Time activity curves (TACs) were extracted within the nucleus accumbens region of interest (ROI) as the average radioactivity in the ROI over time. The occipital lobe, which has the lowest dopamine concentration in the brain, was used as the &quot;reference region&quot; to yield the Kocc measure of [18F]-FDOPA influx rate. Higher [18F]-FDOPA influx rate (kocc) numbers indicate greater relative influx rate and therefore greater dopamine synthesis capacity.</description>
          <population>Participants who had a baseline [18F]-FDOPA PET scan</population>
          <units>min^-1</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="1"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0107"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Montgomery Asberg Depression Rating Scale Following Step 1</title>
        <description>Secondary outcome measured by the total score of the clinician rated MADRS, a measure of depression severity. The MADRS total score range is 0-60, where higher scores indicate greater depression 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 3 weeks (post Step 1)</time_frame>
        <population>Participants with Baseline and Week 3 data available were analyzed</population>
        <group_list>
          <group group_id="O1">
            <title>L-DOPA, Then Placebo</title>
            <description>Step 1 (3 Weeks): Participants will first receive 150 mg of L-DOPA daily in Week 1, 300 mg of L-DOPA in Week 2, and 450 mg L-DOPA in Week 3.&#xD;
Participants will then enter a 1 week taper period.&#xD;
Step 2 (3 Weeks): Participants will receive L-DOPA matching placebo tablets daily.&#xD;
Participants will then enter a 1-week taper period.&#xD;
Carbidopa/levodopa: 150-450mg carbidopa/levodopa 3 times daily&#xD;
Placebo: Carbidopa/levodopa-matched placebo tablet 3 times daily</description>
          </group>
          <group group_id="O2">
            <title>Placebo, Then L-DOPA</title>
            <description>Step 1 (3 Weeks): Participants will receive 3 L-DOPA matching placebo tablets daily. Participants will then enter a 1-week taper period.&#xD;
Step 2 (3 Weeks): Participants will first receive 150 mg of L-DOPA daily in Week 1, 300 mg of L-DOPA in Week 2, and 450 mg L-DOPA in Week 3.&#xD;
Participants will then enter a 1-week taper period.&#xD;
Carbidopa/levodopa: 150-450mg carbidopa/levodopa 3 times daily&#xD;
Placebo: Carbidopa/levodopa-matched placebo tablet 3 times daily</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Montgomery Asberg Depression Rating Scale Following Step 1</title>
          <description>Secondary outcome measured by the total score of the clinician rated MADRS, a measure of depression severity. The MADRS total score range is 0-60, where higher scores indicate greater depression 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 Baseline and Week 3 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="2"/>
                <count group_id="O2" value="2"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.0" spread="9.9"/>
                    <measurement group_id="O2" value="-3.0" spread="2.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Montgomery Asberg Depression Rating Scale Following Step 2</title>
        <description>Secondary outcome measured by the total score of the clinician rated MADRS, a measure of depression severity. The MADRS total score range is 0-60, where higher scores indicate greater depression severity. In contrast to other measures, which were not available at Week 4, Week 4 was selected as the baseline for post-Step 2 change on the MADRS since it followed the taper period taking place between study Steps. 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 Week 4 to Week 7 (post-Step 2)</time_frame>
        <population>Participants with Week 4 and Week 7 data available were analyzed</population>
        <group_list>
          <group group_id="O1">
            <title>L-DOPA, Then Placebo</title>
            <description>Step 1 (3 Weeks): Participants will first receive 150 mg of L-DOPA daily in Week 1, 300 mg of L-DOPA in Week 2, and 450 mg L-DOPA in Week 3.&#xD;
Participants will then enter a 1 week taper period.&#xD;
Step 2 (3 Weeks): Participants will receive L-DOPA matching placebo tablets daily.&#xD;
Participants will then enter a 1-week taper period.&#xD;
Carbidopa/levodopa: 150-450mg carbidopa/levodopa 3 times daily&#xD;
Placebo: Carbidopa/levodopa-matched placebo tablet 3 times daily</description>
          </group>
          <group group_id="O2">
            <title>Placebo, Then L-DOPA</title>
            <description>Step 1 (3 Weeks): Participants will receive 3 L-DOPA matching placebo tablets daily. Participants will then enter a 1-week taper period.&#xD;
Step 2 (3 Weeks): Participants will first receive 150 mg of L-DOPA daily in Week 1, 300 mg of L-DOPA in Week 2, and 450 mg L-DOPA in Week 3.&#xD;
Participants will then enter a 1-week taper period.&#xD;
Carbidopa/levodopa: 150-450mg carbidopa/levodopa 3 times daily&#xD;
Placebo: Carbidopa/levodopa-matched placebo tablet 3 times daily</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Montgomery Asberg Depression Rating Scale Following Step 2</title>
          <description>Secondary outcome measured by the total score of the clinician rated MADRS, a measure of depression severity. The MADRS total score range is 0-60, where higher scores indicate greater depression severity. In contrast to other measures, which were not available at Week 4, Week 4 was selected as the baseline for post-Step 2 change on the MADRS since it followed the taper period taking place between study Steps. 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 4 and Week 7 data available were analyzed</population>
          <units>units on a scale</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="1"/>
                <count group_id="O2" value="1"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.0"/>
                    <measurement group_id="O2" value="2.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Quick Inventory for Depressive Symptomatology (QIDS) Following Step 1</title>
        <description>QIDS-16-item, a participant-rated measure of depressive symptomatology. The total score ranges from 0 to 27, with higher scores indicative of 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 3 weeks (post Step 1)</time_frame>
        <population>Participants with Baseline and Week 3 data available were analyzed</population>
        <group_list>
          <group group_id="O1">
            <title>L-DOPA, Then Placebo</title>
            <description>Step 1 (3 Weeks): Participants will first receive 150 mg of L-DOPA daily in Week 1, 300 mg of L-DOPA in Week 2, and 450 mg L-DOPA in Week 3.&#xD;
Participants will then enter a 1 week taper period.&#xD;
Step 2 (3 Weeks): Participants will receive L-DOPA matching placebo tablets daily.&#xD;
Participants will then enter a 1-week taper period.&#xD;
Carbidopa/levodopa: 150-450mg carbidopa/levodopa 3 times daily&#xD;
Placebo: Carbidopa/levodopa-matched placebo tablet 3 times daily</description>
          </group>
          <group group_id="O2">
            <title>Placebo, Then L-DOPA</title>
            <description>Step 1 (3 Weeks): Participants will receive 3 L-DOPA matching placebo tablets daily. Participants will then enter a 1-week taper period.&#xD;
Step 2 (3 Weeks): Participants will first receive 150 mg of L-DOPA daily in Week 1, 300 mg of L-DOPA in Week 2, and 450 mg L-DOPA in Week 3.&#xD;
Participants will then enter a 1-week taper period.&#xD;
Carbidopa/levodopa: 150-450mg carbidopa/levodopa 3 times daily&#xD;
Placebo: Carbidopa/levodopa-matched placebo tablet 3 times daily</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Quick Inventory for Depressive Symptomatology (QIDS) Following Step 1</title>
          <description>QIDS-16-item, a participant-rated measure of depressive symptomatology. The total score ranges from 0 to 27, with higher scores indicative of 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 Baseline and Week 3 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="1"/>
                <count group_id="O2" value="2"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.0" spread="0.0"/>
                    <measurement group_id="O2" value="-5.0" spread="5.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Quick Inventory for Depressive Symptomatology (QIDS) Following Step 2</title>
        <description>QIDS-16-item, a participant-rated measure of depressive symptomatology. The total score ranges from 0 to 27, with higher scores indicative of greater severity. In contrast to other measures, which were not available at Week 4, Week 4 was selected as the baseline for post-Step 2 change on the QIDS since it followed the taper period taking place between study Steps. 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 Week 4 to Week 7 (post-Step 2)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>L-DOPA, Then Placebo</title>
            <description>Step 1 (3 Weeks): Participants will first receive 150 mg of L-DOPA daily in Week 1, 300 mg of L-DOPA in Week 2, and 450 mg L-DOPA in Week 3.&#xD;
Participants will then enter a 1 week taper period.&#xD;
Step 2 (3 Weeks): Participants will receive L-DOPA matching placebo tablets daily.&#xD;
Participants will then enter a 1-week taper period.&#xD;
Carbidopa/levodopa: 150-450mg carbidopa/levodopa 3 times daily&#xD;
Placebo: Carbidopa/levodopa-matched placebo tablet 3 times daily</description>
          </group>
          <group group_id="O2">
            <title>Placebo, Then L-DOPA</title>
            <description>Step 1 (3 Weeks): Participants will receive 3 L-DOPA matching placebo tablets daily. Participants will then enter a 1-week taper period.&#xD;
Step 2 (3 Weeks): Participants will first receive 150 mg of L-DOPA daily in Week 1, 300 mg of L-DOPA in Week 2, and 450 mg L-DOPA in Week 3.&#xD;
Participants will then enter a 1-week taper period.&#xD;
Carbidopa/levodopa: 150-450mg carbidopa/levodopa 3 times daily&#xD;
Placebo: Carbidopa/levodopa-matched placebo tablet 3 times daily</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Quick Inventory for Depressive Symptomatology (QIDS) Following Step 2</title>
          <description>QIDS-16-item, a participant-rated measure of depressive symptomatology. The total score ranges from 0 to 27, with higher scores indicative of greater severity. In contrast to other measures, which were not available at Week 4, Week 4 was selected as the baseline for post-Step 2 change on the QIDS since it followed the taper period taking place between study Steps. 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>
          <units>units on a scale</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="1"/>
                <count group_id="O2" value="1"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.0"/>
                    <measurement group_id="O2" value="0.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Subjects were monitored over a period of 7 weeks.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>L-DOPA</title>
          <description>This trial entailed the administration of either L-DOPA or placebo in Step 1, followed by crossover to the other treatment assignment in Step 2 (i.e., L-DOPA followed by placebo or placebo followed by L-DOPA). Adverse events are grouped here by treatment assignment (L-DOPA or placebo). This arm pertains to the administration of L-DOPA in Step 1 and Step 2 of the study.</description>
        </group>
        <group group_id="E2">
          <title>Placebo</title>
          <description>This trial entailed the administration of either L-DOPA or placebo in Step 1, followed by crossover to the other treatment assignment in Step 2 (i.e., L-DOPA followed by placebo or placebo followed by L-DOPA). Adverse events are grouped here by treatment assignment (L-DOPA or placebo). This arm pertains to the administration of placebo in Step 1 and Step 2 of the study.</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="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</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="3" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Dry mouth</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Faintness</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Drowsiness</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Increased blood pressure</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </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/NCT04493320
org study id: 7976
secondary id: R01MH123660-01
nct id: NCT04493320
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
Growing evidence suggests that dopamine contributes to key cognitive, emotional, and motor
      functions across the lifespan. In Late-Life Depression (LLD), dysfunction in these areas is
      common, predicts poor outcomes, and manifests as difficulties in motivation and effort along
      with cognitive and gait impairment. While studies of dopamine function in early and midlife
      depression primarily focus on individuals' ability to feel pleasure and respond to rewards,
      they often exclude the cognitive and physical function domains relevant for older adults
      despite a recognized decline in dopamine function with normal aging. The objectives of this
      collaborative R01 proposal between Columbia University/New York State Psychiatric Institute
      and Vanderbilt University Medical Center are to: 1) characterize dopaminergic dysfunction in
      LLD across cognitive, emotional, and motor domains at several levels of analysis (cellular
      Positron Emission Tomography [PET], circuit Magnetic Resonance Imaging [MRI], and behavioral
      / self-report); and 2) examine the responsivity of dopamine-related circuits and behavior to
      stimulation with carbidopa/levodopa (L-DOPA).
Supported by pilot data, this project builds on past work demonstrating that dopamine
      function declines with aging, that dopaminergic dysfunction contributes to deficits in
      behavior, and that L-DOPA administration improves cognitive and motor performance. The
      long-term goal of this line of research is to determine how dopaminergic dysfunction
      contributes to clinical presentations of LLD, how responsive behavioral symptoms are to
      modulation of dopamine function, and to identify novel targets for future interventions.
      Investigator's approach is to enroll 30 psychiatrically healthy elders and 60 depressed
      elders at Columbia/NYSPI exhibiting either slowed processing speed or slowed gait speed.
      Participants will undergo thorough clinical evaluations and complete PET imaging measuring
      different aspects of the brain's dopamine system, neuromelanin-sensitive MRI measurement of
      longterm dopamine transmission, functional MRI focused on effort-based decision making and
      reward processing, a comprehensive neurocognitive evaluation, a physical performance
      evaluation, and measurement of inflammatory markers. To assess responsivity of the dopamine
      system to modulation, depressed subjects then will be randomized to L-DOPA or placebo for 3
      weeks, followed by repeat multimodal MRI and cognitive/behavioral assessments. In a second
      phase, participants will receive the opposite intervention for an additional 3 weeks followed
      by clinical and cognitive assessments only. This proposal is significant and innovative, as
      no prior published study has comprehensively examined dopamine-dependent behaviors in LLD.
      This will inform treatment approaches focusing on facilitating cognition and movement,
      reducing the effort cost of voluntary behavior, and promoting behavioral activation.
allocation: Randomized
intervention model: Crossover Assignment
intervention model description: Double blind crossover study
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Change in Effort Expenditure for Rewards Task (EEfRT) Following Step 1
time frame: Change from Baseline to 3 weeks (post Step 1)
description: In this task participants decide whether to work harder for a larger reward (high number of finger presses with their pinky) or expend less energy (low number of presses with a dominant index finger) for a lesser reward, with lower rewards being $1 dollar and higher rewards ranging from $1.20 to $5. Participants receive information about the probability of winning on each trial regardless of their pick and one trial from each run is randomly picked for payout. The primary output on this task is the percentage of time participants choose the high cost / high reward option on the EEfRT. 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.
This task was not completed following Step 2 of the study, so there are no EEfRT data reported for change in task performance following Step 2.
measure: Change in Digit Symbol Test Following Step 1
time frame: Change from Baseline to 3 weeks (post Step 1)
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: Change in Digit Symbol Test Following Step 2
time frame: Change from Week 3 to Week 7 (post-Step 2)
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: Change in Pattern Comparison Test Following Step 1
time frame: Change from Baseline to 3 weeks (post Step 1)
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: Change in Pattern Comparison Test Following Step 2
time frame: Change from Week 3 to Week 7 (post-Step 2)
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: Change in Letter Comparison Test Following Step 1
time frame: Change from Baseline to 3 weeks (post Step 1)
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.
measure: Change in Letter Comparison Test Following Step 2
time frame: Change from Week 3 to Week 7 (post-Step 2)
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.
measure: Change in Single Task Gait Speed Test Following Step 1
time frame: Change from Baseline to 3 weeks (post Step 1)
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: Change in Single Task Gait Speed Test Following Step 2
time frame: Change from Week 3 to Week 7 (post-Step 2)
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: [18F]-FDOPA PET Measure in Striatal Region of Interest
time frame: Baseline (prior to LDOPA or placebo administration)
description: [18F]-FDOPA PET quantifies dopamine synthesis capacity in specific brain regions. Lower [18F]-FDOPA uptake in the striatum has been associated with increased depression severity and worse cognitive and motor function in patients. Because [18F]-FDOPA uptake may be sensitive to deficits in dopamine synthesis capacity in older depressed patients, in this study depressed participants at baseline underwent a PET scan to quantify relative [18F]-FDOPA influx rate in the nucleus accumbens bilaterally. Time activity curves (TACs) were extracted within the nucleus accumbens region of interest (ROI) as the average radioactivity in the ROI over time. The occipital lobe, which has the lowest dopamine concentration in the brain, was used as the "reference region" to yield the Kocc measure of [18F]-FDOPA influx rate. Higher [18F]-FDOPA influx rate (kocc) numbers indicate greater relative influx rate and therefore greater dopamine synthesis capacity.
measure: Change in Montgomery Asberg Depression Rating Scale Following Step 1
time frame: Change from Baseline to 3 weeks (post Step 1)
description: Secondary outcome measured by the total score of the clinician rated MADRS, a measure of depression severity. The MADRS total score range is 0-60, where higher scores indicate greater depression 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: Change in Montgomery Asberg Depression Rating Scale Following Step 2
time frame: Change from Week 4 to Week 7 (post-Step 2)
description: Secondary outcome measured by the total score of the clinician rated MADRS, a measure of depression severity. The MADRS total score range is 0-60, where higher scores indicate greater depression severity. In contrast to other measures, which were not available at Week 4, Week 4 was selected as the baseline for post-Step 2 change on the MADRS since it followed the taper period taking place between study Steps. 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: Change in Quick Inventory for Depressive Symptomatology (QIDS) Following Step 1
time frame: Change from Baseline to 3 weeks (post Step 1)
description: QIDS-16-item, a participant-rated measure of depressive symptomatology. The total score ranges from 0 to 27, with higher scores indicative of 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: Change in Quick Inventory for Depressive Symptomatology (QIDS) Following Step 2
time frame: Change from Week 4 to Week 7 (post-Step 2)
description: QIDS-16-item, a participant-rated measure of depressive symptomatology. The total score ranges from 0 to 27, with higher scores indicative of greater severity. In contrast to other measures, which were not available at Week 4, Week 4 was selected as the baseline for post-Step 2 change on the QIDS since it followed the taper period taking place between study Steps. 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, Then Placebo
arm group type: Experimental
description: Step 1 (3 Weeks): Participants will first receive 150 mg of L-DOPA daily in Week 1, 300 mg of L-DOPA in Week 2, and 450 mg L-DOPA in Week 3.
Participants will then enter a 1 week taper period.
Step 2 (3 Weeks): Participants will receive L-DOPA matching placebo tablets daily.
Participants will then enter a 1-week taper period.
arm group label: Placebo, Then L-DOPA
arm group type: Experimental
description: Step 1 (3 Weeks): Participants will receive 3 L-DOPA matching placebo tablets daily. Participants will then enter a 1-week taper period.
Step 2 (3 Weeks): Participants will first receive 150 mg of L-DOPA daily in Week 1, 300 mg of L-DOPA in Week 2, and 450 mg L-DOPA in Week 3.
Participants will then enter a 1-week taper period.
intervention type: Drug
intervention name: Carbidopa/levodopa
description: 150-450mg carbidopa/levodopa 3 times daily
arm group label: L-DOPA, Then Placebo
arm group label: Placebo, Then L-DOPA
other name: L-DOPA
other name: Sinemet
intervention type: Drug
intervention name: Placebo
description: Carbidopa/levodopa-matched placebo tablet 3 times daily
arm group label: L-DOPA, Then Placebo
arm group label: Placebo, Then L-DOPA
other name: Placebo tablet
criteria: 
gender: All
minimum age: 60 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Bret R 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: 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: 