<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/NCT02968433</url>
  </required_header>
  <id_info>
    <org_study_id>IRB 38417</org_study_id>
    <nct_id>NCT02968433</nct_id>
  </id_info>
  <brief_title>The Stanford Parkinson's Disease Plasma Study</brief_title>
  <acronym>SPDP</acronym>
  <official_title>The Stanford Parkinson's Disease Plasma (SPDP) Study: Intravenously-Administered Plasma From Young Donors for Treatment of Moderate Parkinson's Disease</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Stanford University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Stanford University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to demonstrate that young plasma infusions can be performed&#xD;
      safely in patients with Parkinson's Disease (PD). Secondary outcomes will include behavioral&#xD;
      and laboratory data that will support the next study that will inquire whether young plasma&#xD;
      infusions improve or slow the progression of cognitive, mood and/or motor impairment and rate&#xD;
      markers of the disease.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Parkinson's disease (PD) is a neurodegenerative disease that affects over 1.6 million people&#xD;
      in the United States and whose incidence increases with age, affecting over 1% of people over&#xD;
      the age of 65. The neuropathological processes involved in PD are widespread throughout the&#xD;
      brain, and are reflected in a constellation of motor, cognitive, mood and other non-motor&#xD;
      symptoms. Treatments to date have largely focused on dopamine replacement strategies or deep&#xD;
      brain stimulation, both symptomatic treatments.&#xD;
&#xD;
      As neurodegenerative diseases progress, there are major changes throughout the body and&#xD;
      brain. These changes are transmitted in the body via the circulatory system between organs,&#xD;
      tissues and cells. Recent findings from multiple laboratories have shown that infusions of&#xD;
      young plasma into aging rodents can have beneficial effects on cognitive functions. This&#xD;
      suggests that the circulating components of plasma can improve cognitive and disease-relevant&#xD;
      symptoms. This has motivated the field to treat multiple disorders with blood products and&#xD;
      their constituent active components.&#xD;
&#xD;
      The established safety of blood transfusions allows the investigators to test whether&#xD;
      infusions of young plasma can ease the neurological symptoms in human subjects with&#xD;
      neurodegenerative diseases. A related study of plasma infusions has already been completed at&#xD;
      Stanford in patients with Alzheimer's disease (ClinicalTrials.gov identifier NCT02256306).&#xD;
&#xD;
      The investigator proposes to test the safety and efficacy of transfusing young plasma into PD&#xD;
      participants, in order to establish its effects on motor and cognitive functions in&#xD;
      participants in a Phase 1 study. The successful completion of this study will inform the&#xD;
      design of future, larger and multicenter studies with the goal to determine whether infusions&#xD;
      of young plasma can ameliorate the neurodegenerative symptoms and underlying pathophysiology&#xD;
      in Parkinson's disease.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 2016</start_date>
  <completion_date type="Actual">December 2019</completion_date>
  <primary_completion_date type="Actual">December 2019</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Related and Unrelated Adverse Events</measure>
    <time_frame>8 weeks</time_frame>
    <description>The primary outcome measure is the number of adverse events across all participants that might be related to young plasma infusions as a novel treatment to Parkinson's Disease symptoms. Adverse events were categorized as probably, possibly, or not related to the study intervention.</description>
  </primary_outcome>
  <other_outcome>
    <measure>Change in Quantitative Data of Cognitive Ability (Neuropsychological Battery)</measure>
    <time_frame>8 weeks</time_frame>
    <description>Change in quantitative data of cognitive ability. Raw scores and normative scores were calculated for all measures according to standardized procedures across all 3 time points.&#xD;
The cognitive test battery included:&#xD;
Trail Making Test Part A (0-92; lower scores indicate better performance) and B (0-300; lower scores indicate better performance)&#xD;
Digit Symbol Modalities Test (Oral: 0-110 and Written: 0-110; higher scores indicate better performance)&#xD;
Animal Naming Test (0-no maximum; higher scores indicate better performance)&#xD;
Controlled Oral Word Association Test (COWAT) (0-no maximum; higher score indicates better performance)&#xD;
CogStateTM Groton Maze Learning Test (GML) (minimum score is 0; lower scores indicate better performance)&#xD;
Wechsler Abbreviated Scale of Intelligence-II (WASI-II) Block Design (0-71; higher scores indicate better performance) and Matrix Reasoning (0-30; higher scores indicate better performance)</description>
  </other_outcome>
  <other_outcome>
    <measure>Change in Quality of Life</measure>
    <time_frame>8 weeks</time_frame>
    <description>Quality of life (QOL) changes were tracked using the self-report Parkinson's Disease Questionnaire-39 (PDQ-39). The PDQ-39 includes 8 sub-scales: Mobility (raw score range 0-40), Activities of Daily Living (raw score range 0-24), Emotional Well-Being (raw score range 0-24), Stigma (raw score range 0-16), Social Support (raw score range 0-12), Cognition (raw score range 0-16), Communication (raw score range 0-12), and Bodily Discomfort (raw score range 0-12). Subscales scores are totaled then converted to a percentage to calculate the Total score (0 to 100, higher scores indicating the more problems). Ratings are based on participant experiences over the course of the prior month. Lower scores represent better quality of life for all scores.</description>
  </other_outcome>
  <other_outcome>
    <measure>Change in Quantitative Data of Motor Movements up to 8 Weeks</measure>
    <time_frame>8 weeks</time_frame>
    <description>The second outcome measure is the change in the quantitative data of current motor movement ability.&#xD;
Patients completed a repetitive Wrist Flexion Extension (rWFE) task with both hands, off therapy at the baseline, immediate-post, and delayed-post visits. Patients were instructed to flex and extend their hands at the wrist as quickly as possible after a &quot;Go&quot; command was given and to stop when instructed. This movement was self-paced, lasted 30 seconds, and was measured using wearable sensors attached to the dorsum of each hand (Motus Bioengineering, Inc.). Variables of interest included the mean angular velocity (Vrms), the variability of mean angular velocity, (CV Vrms), and rhythmicity, defined as the regularity of the interstrike interval (CV ISI). MA = more affected; LA = less affected.</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">16</enrollment>
  <condition>Parkinson Disease(PD)</condition>
  <arm_group>
    <arm_group_label>Infusions of Young Plasma</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>All participants will undergo neuropsychological, neuropsychiatric, and kinematic assessments prior to receiving infusions of young plasma as the treatment.&#xD;
Participants will receive 1 unit of young plasma, twice a week over a four week duration.&#xD;
After the four weeks of plasma infusions, participants will undergo neuropsychological, neuropsychiatric and kinematic reassessments. No deception will be used.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Infusions of young plasma</intervention_name>
    <description>Participants will receive four twice- weekly infusions of 1 unit young plasma (male, ages between 18-25)</description>
    <arm_group_label>Infusions of Young Plasma</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  A diagnosis of clinically probable or established Parkinson's Disease (MDS criteria)&#xD;
&#xD;
          -  Subject must be on a stable dose of dopaminergic medication and/or Deep Brain&#xD;
             Stimulation (DBS) parameters for at least 4 weeks prior to screening and for the&#xD;
             duration of the study&#xD;
&#xD;
          -  Subject must be competent to sign consent&#xD;
&#xD;
          -  Subject must be willing to commit to being available for testing and infusions for 6&#xD;
             consecutive weeks (2 testing consecutive weeks, 4 infusion consecutive weeks) followed&#xD;
             by two visits a month after final infusion.&#xD;
&#xD;
          -  The availability of a study partner who knows the patient well and is willing to&#xD;
             accompany the subject to all trial (optional if participant is able to consent and&#xD;
             travel by self)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  The participation in any other interventional clinical trial&#xD;
&#xD;
          -  The inability to travel to Stanford&#xD;
&#xD;
          -  Inability to walk without assistance in the off or on medication state&#xD;
&#xD;
          -  The clinically determined presence of dementia&#xD;
&#xD;
          -  A clinical suspicion/diagnosis of Multiple System Atrophy (MSA), Progressive&#xD;
             Supranuclear Palsy (PSP), Lewy Body Dementia (LBD), Essential Tremor (ET)&#xD;
&#xD;
          -  Subject's pregnancy or likelihood of pregnancy within the next 6 months.&#xD;
&#xD;
          -  Subject's positive test results for Hepatitis B, Hepatitis C or HIV at screening&#xD;
&#xD;
          -  Any other condition or situation that the investigator believes may interfere with the&#xD;
             safety of the subject or the intent and conduct of the study&#xD;
&#xD;
          -  Subject's medical history of:&#xD;
&#xD;
        Stroke Anaphylaxis Gout- may cause an increase in uric acid Prior adverse reaction to any&#xD;
        human blood product Any history of a blood coagulation disorder or hypercoagulability&#xD;
        Congestive heart failure Uncontrolled hypertension Renal failure Prior intolerance to&#xD;
        intravenous fluids Recent history of uncontrolled atrial fibrillation immunoglobulin A&#xD;
        deficiency (by history)&#xD;
&#xD;
          -  Subject's relation to medications or other treatments:&#xD;
&#xD;
          -  Any concurrent use of an anticoagulant therapy. Antiplatelet drugs (e.g., aspirin or&#xD;
             clopidogrel) are acceptable.&#xD;
&#xD;
          -  The use of Inosine, which may alter urate levels&#xD;
&#xD;
          -  Initiation or change in the dosage of a cholinesterase inhibitor or memantine during&#xD;
             the trial. A participant already on a cholinesterase inhibitor or memantine must be on&#xD;
             a stable dose for at least one month prior to Screening.&#xD;
&#xD;
          -  Concurrent participation in another interventional treatment trial for Parkinson's&#xD;
             disease. If there was prior participation, the last dose of the investigational agent&#xD;
             must have been at least 6 months prior to Screening.&#xD;
&#xD;
          -  Treatment with any human blood product, including intravenous immunoglobulin, during&#xD;
             the 6 months prior to Screening or during the trial.&#xD;
&#xD;
          -  Concurrent daily treatment with benzodiazepines, typical or atypical antipsychotics,&#xD;
             long-acting opioids, or other medications that, in the investigator's opinion,&#xD;
             interfere with cognition. Intermittent treatment with short-acting benzodiazepines or&#xD;
             atypical antipsychotics may be permitted, provided that no dose is administered within&#xD;
             the 72 hours preceding any cognitive assessment.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>50 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Helen Bronte-Stewart, MS, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Stanford University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Stanford Movement Disorders Clinic</name>
      <address>
        <city>Stanford</city>
        <state>California</state>
        <zip>94304</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Sha SJ, Deutsch GK, Tian L, Richardson K, Coburn M, Gaudioso JL, Marcal T, Solomon E, Boumis A, Bet A, Mennes M, van Oort E, Beckmann CF, Braithwaite SP, Jackson S, Nikolich K, Stephens D, Kerchner GA, Wyss-Coray T. Safety, Tolerability, and Feasibility of Young Plasma Infusion in the Plasma for Alzheimer Symptom Amelioration Study: A Randomized Clinical Trial. JAMA Neurol. 2019 Jan 1;76(1):35-40. doi: 10.1001/jamaneurol.2018.3288.</citation>
    <PMID>30383097</PMID>
  </reference>
  <reference>
    <citation>Villeda SA, Luo J, Mosher KI, Zou B, Britschgi M, Bieri G, Stan TM, Fainberg N, Ding Z, Eggel A, Lucin KM, Czirr E, Park JS, Couillard-Despres S, Aigner L, Li G, Peskind ER, Kaye JA, Quinn JF, Galasko DR, Xie XS, Rando TA, Wyss-Coray T. The ageing systemic milieu negatively regulates neurogenesis and cognitive function. Nature. 2011 Aug 31;477(7362):90-4. doi: 10.1038/nature10357.</citation>
    <PMID>21886162</PMID>
  </reference>
  <reference>
    <citation>Villeda SA, Plambeck KE, Middeldorp J, Castellano JM, Mosher KI, Luo J, Smith LK, Bieri G, Lin K, Berdnik D, Wabl R, Udeochu J, Wheatley EG, Zou B, Simmons DA, Xie XS, Longo FM, Wyss-Coray T. Young blood reverses age-related impairments in cognitive function and synaptic plasticity in mice. Nat Med. 2014 Jun;20(6):659-63. doi: 10.1038/nm.3569. Epub 2014 May 4.</citation>
    <PMID>24793238</PMID>
  </reference>
  <results_reference>
    <citation>Parker JE, Martinez A, Deutsch GK, Prabhakar V, Lising M, Kapphahn KI, Anidi CM, Neuville R, Coburn M, Shah N, Bronte-Stewart HM. Safety of Plasma Infusions in Parkinson's Disease. Mov Disord. 2020 Nov;35(11):1905-1913. doi: 10.1002/mds.28198. Epub 2020 Jul 7.</citation>
    <PMID>32633860</PMID>
  </results_reference>
  <verification_date>December 2020</verification_date>
  <study_first_submitted>November 14, 2016</study_first_submitted>
  <study_first_submitted_qc>November 16, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 18, 2016</study_first_posted>
  <results_first_submitted>July 13, 2020</results_first_submitted>
  <results_first_submitted_qc>December 3, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">December 30, 2020</results_first_posted>
  <last_update_submitted>December 3, 2020</last_update_submitted>
  <last_update_submitted_qc>December 3, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">December 30, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Stanford University</investigator_affiliation>
    <investigator_full_name>Helen M. Bronte-Stewart</investigator_full_name>
    <investigator_title>Primary Investigator</investigator_title>
  </responsible_party>
  <keyword>Young Male Plasma</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Parkinson Disease</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>July 23, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/33/NCT02968433/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Infusions of Young Plasma</title>
          <description>All participants will undergo neuropsychological, neuropsychiatric, and kinematic assessments prior to receiving infusions of young plasma as the treatment.&#xD;
Participants will receive 1 unit of young plasma, twice a week over a four week duration.&#xD;
After the four weeks of plasma infusions, participants will undergo neuropsychological, neuropsychiatric and kinematic reassessments. No deception will be used.&#xD;
Infusions of young plasma: Participants will receive four twice- weekly infusions of 1 unit young plasma (male, ages between 18-25)</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="16"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="15"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Participants who completed the study</population>
      <group_list>
        <group group_id="B1">
          <title>Infusions of Young Plasma</title>
          <description>All participants will undergo neuropsychological, neuropsychiatric, and kinematic assessments prior to receiving infusions of young plasma as the treatment.&#xD;
Participants will receive 1 unit of young plasma, twice a week over a four week duration.&#xD;
After the four weeks of plasma infusions, participants will undergo neuropsychological, neuropsychiatric and kinematic reassessments. No deception will be used.&#xD;
Infusions of young plasma: Participants will receive four twice- weekly infusions of 1 unit young plasma (male, ages between 18-25)</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="15"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <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="63" spread="8.3"/>
                  </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="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Number of Related and Unrelated Adverse Events</title>
        <description>The primary outcome measure is the number of adverse events across all participants that might be related to young plasma infusions as a novel treatment to Parkinson's Disease symptoms. Adverse events were categorized as probably, possibly, or not related to the study intervention.</description>
        <time_frame>8 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Infusions of Young Plasma</title>
            <description>All participants will undergo neuropsychological, neuropsychiatric, and kinematic assessments prior to receiving infusions of young plasma as the treatment.&#xD;
Participants will receive 1 unit of young plasma, twice a week over a four week duration.&#xD;
After the four weeks of plasma infusions, participants will undergo neuropsychological, neuropsychiatric and kinematic reassessments. No deception will be used.&#xD;
Infusions of young plasma: Participants will receive four twice- weekly infusions of 1 unit young plasma (male, ages between 18-25)</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Related and Unrelated Adverse Events</title>
          <description>The primary outcome measure is the number of adverse events across all participants that might be related to young plasma infusions as a novel treatment to Parkinson's Disease symptoms. Adverse events were categorized as probably, possibly, or not related to the study intervention.</description>
          <units>events</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="16"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Number of probably related AEs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Number of possibly related AEs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Number of unrelated AEs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="36"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Change in Quantitative Data of Cognitive Ability (Neuropsychological Battery)</title>
        <description>Change in quantitative data of cognitive ability. Raw scores and normative scores were calculated for all measures according to standardized procedures across all 3 time points.&#xD;
The cognitive test battery included:&#xD;
Trail Making Test Part A (0-92; lower scores indicate better performance) and B (0-300; lower scores indicate better performance)&#xD;
Digit Symbol Modalities Test (Oral: 0-110 and Written: 0-110; higher scores indicate better performance)&#xD;
Animal Naming Test (0-no maximum; higher scores indicate better performance)&#xD;
Controlled Oral Word Association Test (COWAT) (0-no maximum; higher score indicates better performance)&#xD;
CogStateTM Groton Maze Learning Test (GML) (minimum score is 0; lower scores indicate better performance)&#xD;
Wechsler Abbreviated Scale of Intelligence-II (WASI-II) Block Design (0-71; higher scores indicate better performance) and Matrix Reasoning (0-30; higher scores indicate better performance)</description>
        <time_frame>8 weeks</time_frame>
        <population>Participants who completed the protocol are included in the analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Baseline</title>
            <description>Before any treatment-related intervention began</description>
          </group>
          <group group_id="O2">
            <title>Immediate-post Evaluation</title>
            <description>Immediately after the last plasma infusion</description>
          </group>
          <group group_id="O3">
            <title>Delayed-post Evaluation</title>
            <description>4-weeks after the last plasma infusion</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Quantitative Data of Cognitive Ability (Neuropsychological Battery)</title>
          <description>Change in quantitative data of cognitive ability. Raw scores and normative scores were calculated for all measures according to standardized procedures across all 3 time points.&#xD;
The cognitive test battery included:&#xD;
Trail Making Test Part A (0-92; lower scores indicate better performance) and B (0-300; lower scores indicate better performance)&#xD;
Digit Symbol Modalities Test (Oral: 0-110 and Written: 0-110; higher scores indicate better performance)&#xD;
Animal Naming Test (0-no maximum; higher scores indicate better performance)&#xD;
Controlled Oral Word Association Test (COWAT) (0-no maximum; higher score indicates better performance)&#xD;
CogStateTM Groton Maze Learning Test (GML) (minimum score is 0; lower scores indicate better performance)&#xD;
Wechsler Abbreviated Scale of Intelligence-II (WASI-II) Block Design (0-71; higher scores indicate better performance) and Matrix Reasoning (0-30; higher scores indicate better performance)</description>
          <population>Participants who completed the protocol are included in the analysis.</population>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="15"/>
                <count group_id="O2" value="15"/>
                <count group_id="O3" value="15"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>WASI-II Block Construction</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="34.73" lower_limit="27.45" upper_limit="42.02"/>
                    <measurement group_id="O2" value="35.60" lower_limit="28.32" upper_limit="42.88"/>
                    <measurement group_id="O3" value="37.47" lower_limit="30.18" upper_limit="44.75"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>WASI-II Matrix Reasoning</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="17.47" lower_limit="14.87" upper_limit="20.06"/>
                    <measurement group_id="O2" value="17.27" lower_limit="14.67" upper_limit="19.86"/>
                    <measurement group_id="O3" value="20.13" lower_limit="17.54" upper_limit="22.73"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Symbol Digit Modalities Test - Written</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="44.80" lower_limit="39.14" upper_limit="50.46"/>
                    <measurement group_id="O2" value="47.07" lower_limit="41.40" upper_limit="52.73"/>
                    <measurement group_id="O3" value="49.40" lower_limit="43.74" upper_limit="55.06"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Symbol Digit Modalities Test - Oral</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="53.67" lower_limit="46.89" upper_limit="60.44"/>
                    <measurement group_id="O2" value="57.40" lower_limit="50.62" upper_limit="64.18"/>
                    <measurement group_id="O3" value="57.73" lower_limit="50.96" upper_limit="64.51"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Trail Making Test-A</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="32.53" lower_limit="27.63" upper_limit="37.44"/>
                    <measurement group_id="O2" value="29.27" lower_limit="24.36" upper_limit="34.17"/>
                    <measurement group_id="O3" value="29.07" lower_limit="24.16" upper_limit="33.97"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Trail Making Test-B</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="83.20" lower_limit="62.64" upper_limit="103.76"/>
                    <measurement group_id="O2" value="72.87" lower_limit="52.31" upper_limit="93.42"/>
                    <measurement group_id="O3" value="73.53" lower_limit="52.98" upper_limit="94.09"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Phonemic fluency (COWAT; Letters-FAS)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="43.13" lower_limit="34.75" upper_limit="47.52"/>
                    <measurement group_id="O2" value="44.73" lower_limit="38.35" upper_limit="51.12"/>
                    <measurement group_id="O3" value="48.07" lower_limit="41.68" upper_limit="54.45"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Semantic fluency (Animal naming)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="21.40" lower_limit="19.17" upper_limit="23.63"/>
                    <measurement group_id="O2" value="22.40" lower_limit="20.17" upper_limit="24.63"/>
                    <measurement group_id="O3" value="23.07" lower_limit="20.84" upper_limit="25.29"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>CogState (GML)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="71.47" lower_limit="53.15" upper_limit="89.79"/>
                    <measurement group_id="O2" value="54.87" lower_limit="36.55" upper_limit="73.19"/>
                    <measurement group_id="O3" value="60.53" lower_limit="42.21" upper_limit="78.85"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Change in Quality of Life</title>
        <description>Quality of life (QOL) changes were tracked using the self-report Parkinson's Disease Questionnaire-39 (PDQ-39). The PDQ-39 includes 8 sub-scales: Mobility (raw score range 0-40), Activities of Daily Living (raw score range 0-24), Emotional Well-Being (raw score range 0-24), Stigma (raw score range 0-16), Social Support (raw score range 0-12), Cognition (raw score range 0-16), Communication (raw score range 0-12), and Bodily Discomfort (raw score range 0-12). Subscales scores are totaled then converted to a percentage to calculate the Total score (0 to 100, higher scores indicating the more problems). Ratings are based on participant experiences over the course of the prior month. Lower scores represent better quality of life for all scores.</description>
        <time_frame>8 weeks</time_frame>
        <population>Participants who completed the protocol are included in the analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Baseline</title>
            <description>Before any treatment-related intervention began</description>
          </group>
          <group group_id="O2">
            <title>Immediate-post Evaluation</title>
            <description>Immediately after the last plasma infusion</description>
          </group>
          <group group_id="O3">
            <title>Delayed-post Evaluation</title>
            <description>4-weeks after the last plasma infusion</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Quality of Life</title>
          <description>Quality of life (QOL) changes were tracked using the self-report Parkinson's Disease Questionnaire-39 (PDQ-39). The PDQ-39 includes 8 sub-scales: Mobility (raw score range 0-40), Activities of Daily Living (raw score range 0-24), Emotional Well-Being (raw score range 0-24), Stigma (raw score range 0-16), Social Support (raw score range 0-12), Cognition (raw score range 0-16), Communication (raw score range 0-12), and Bodily Discomfort (raw score range 0-12). Subscales scores are totaled then converted to a percentage to calculate the Total score (0 to 100, higher scores indicating the more problems). Ratings are based on participant experiences over the course of the prior month. Lower scores represent better quality of life for all scores.</description>
          <population>Participants who completed the protocol are included in the analysis.</population>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="15"/>
                <count group_id="O2" value="15"/>
                <count group_id="O3" value="15"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Total PDQ-39 Score</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="71.81" lower_limit="59.51" upper_limit="84.10"/>
                    <measurement group_id="O2" value="66.73" lower_limit="54.49" upper_limit="78.98"/>
                    <measurement group_id="O3" value="64.40" lower_limit="52.16" upper_limit="76.64"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Mobility</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="17.33" lower_limit="13.38" upper_limit="21.28"/>
                    <measurement group_id="O2" value="16.47" lower_limit="12.53" upper_limit="20.41"/>
                    <measurement group_id="O3" value="15.80" lower_limit="11.86" upper_limit="19.74"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Activities of Daily Living</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12.05" lower_limit="10.29" upper_limit="13.82"/>
                    <measurement group_id="O2" value="11.60" lower_limit="9.85" upper_limit="13.35"/>
                    <measurement group_id="O3" value="10.53" lower_limit="8.79" upper_limit="12.28"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Emotional Well-Being</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10.60" lower_limit="7.75" upper_limit="13.45"/>
                    <measurement group_id="O2" value="10.13" lower_limit="7.30" upper_limit="12.97"/>
                    <measurement group_id="O3" value="10.00" lower_limit="7.16" upper_limit="12.84"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Stigma</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.42" lower_limit="6.22" upper_limit="8.63"/>
                    <measurement group_id="O2" value="6.20" lower_limit="5.01" upper_limit="7.39"/>
                    <measurement group_id="O3" value="5.53" lower_limit="4.34" upper_limit="6.72"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Social support</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.57" lower_limit="3.99" upper_limit="7.16"/>
                    <measurement group_id="O2" value="5.00" lower_limit="3.43" upper_limit="6.57"/>
                    <measurement group_id="O3" value="5.33" lower_limit="3.76" upper_limit="6.90"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cognition</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.90" lower_limit="5.53" upper_limit="8.28"/>
                    <measurement group_id="O2" value="6.87" lower_limit="5.50" upper_limit="8.23"/>
                    <measurement group_id="O3" value="6.80" lower_limit="5.43" upper_limit="8.17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Communication</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.33" lower_limit="4.31" upper_limit="6.36"/>
                    <measurement group_id="O2" value="5.20" lower_limit="4.19" upper_limit="6.21"/>
                    <measurement group_id="O3" value="4.60" lower_limit="3.59" upper_limit="5.61"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Bodily Discomfort</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.53" lower_limit="5.25" upper_limit="7.82"/>
                    <measurement group_id="O2" value="5.27" lower_limit="4.00" upper_limit="6.53"/>
                    <measurement group_id="O3" value="5.80" lower_limit="4.53" upper_limit="7.07"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Change in Quantitative Data of Motor Movements up to 8 Weeks</title>
        <description>The second outcome measure is the change in the quantitative data of current motor movement ability.&#xD;
Patients completed a repetitive Wrist Flexion Extension (rWFE) task with both hands, off therapy at the baseline, immediate-post, and delayed-post visits. Patients were instructed to flex and extend their hands at the wrist as quickly as possible after a &quot;Go&quot; command was given and to stop when instructed. This movement was self-paced, lasted 30 seconds, and was measured using wearable sensors attached to the dorsum of each hand (Motus Bioengineering, Inc.). Variables of interest included the mean angular velocity (Vrms), the variability of mean angular velocity, (CV Vrms), and rhythmicity, defined as the regularity of the interstrike interval (CV ISI). MA = more affected; LA = less affected.</description>
        <time_frame>8 weeks</time_frame>
        <population>Patients who completed the rWFE task at baseline and at both outcome visits and who had analyzable data are included in the analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Baseline</title>
            <description>Baseline rWFE task was completed before any treatment-related intervention.</description>
          </group>
          <group group_id="O2">
            <title>Immediate-post Evaluation</title>
            <description>Immediate-post rWFE task was completed on the day following the last infusion.</description>
          </group>
          <group group_id="O3">
            <title>Delayed-post Evaluation</title>
            <description>Delayed-post rWFE task was completed 4-weeks after the final infusion.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Quantitative Data of Motor Movements up to 8 Weeks</title>
          <description>The second outcome measure is the change in the quantitative data of current motor movement ability.&#xD;
Patients completed a repetitive Wrist Flexion Extension (rWFE) task with both hands, off therapy at the baseline, immediate-post, and delayed-post visits. Patients were instructed to flex and extend their hands at the wrist as quickly as possible after a &quot;Go&quot; command was given and to stop when instructed. This movement was self-paced, lasted 30 seconds, and was measured using wearable sensors attached to the dorsum of each hand (Motus Bioengineering, Inc.). Variables of interest included the mean angular velocity (Vrms), the variability of mean angular velocity, (CV Vrms), and rhythmicity, defined as the regularity of the interstrike interval (CV ISI). MA = more affected; LA = less affected.</description>
          <population>Patients who completed the rWFE task at baseline and at both outcome visits and who had analyzable data are included in the analysis.</population>
          <units>Degrees/sec</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="12"/>
                <count group_id="O2" value="12"/>
                <count group_id="O3" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>MA Vrms</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="305.13" lower_limit="196.72" upper_limit="413.54"/>
                    <measurement group_id="O2" value="339.66" lower_limit="231.24" upper_limit="448.07"/>
                    <measurement group_id="O3" value="312.39" lower_limit="203.98" upper_limit="420.81"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>MA CV Vrms</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.29" lower_limit="0.2" upper_limit="0.38"/>
                    <measurement group_id="O2" value="0.19" lower_limit="0.10" upper_limit="0.29"/>
                    <measurement group_id="O3" value="0.26" lower_limit="0.17" upper_limit="0.35"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>MA CV ISI</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.16" lower_limit="0.07" upper_limit="0.26"/>
                    <measurement group_id="O2" value="0.11" lower_limit="0.01" upper_limit="0.20"/>
                    <measurement group_id="O3" value="0.17" lower_limit="0.08" upper_limit="0.27"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>LA Vrms</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="414.47" lower_limit="295.08" upper_limit="533.86"/>
                    <measurement group_id="O2" value="411.26" lower_limit="291.87" upper_limit="530.65"/>
                    <measurement group_id="O3" value="403.00" lower_limit="283.61" upper_limit="522.39"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>LA CV Vrms</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.16" lower_limit="0.09" upper_limit="0.22"/>
                    <measurement group_id="O2" value="0.17" lower_limit="0.12" upper_limit="0.24"/>
                    <measurement group_id="O3" value="0.18" lower_limit="0.11" upper_limit="0.24"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>LA CV ISI</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.09" lower_limit="0.05" upper_limit="0.14"/>
                    <measurement group_id="O2" value="0.09" lower_limit="0.04" upper_limit="0.13"/>
                    <measurement group_id="O3" value="0.10" lower_limit="0.05" upper_limit="0.15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse events were monitored during the entirety of the trial, starting at baseline and continuing through the 4 week post-infusion mark (8 week total).</time_frame>
      <desc>Adverse events were categorized using the CTCAE v4.0.</desc>
      <group_list>
        <group group_id="E1">
          <title>Infusions of Young Plasma</title>
          <description>All participants will undergo neuropsychological, neuropsychiatric, and kinematic assessments prior to receiving infusions of young plasma as the treatment.&#xD;
Participants will receive 1 unit of young plasma, twice a week over a four week duration.&#xD;
After the four weeks of plasma infusions, participants will undergo neuropsychological, neuropsychiatric and kinematic reassessments. No deception will be used.&#xD;
Infusions of young plasma: Participants will receive four twice- weekly infusions of 1 unit young plasma (male, ages between 18-25)</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="16"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="13" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Bloating</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Stomach pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Gastrointestinal disorders</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Chest tightness</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Flu-like symptoms</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Tremor</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Involuntary movement</sub_title>
                <counts group_id="E1" events="8" subjects_affected="5" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Sleep disturbance</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Musculoskeletal and connective tissue disorder</sub_title>
                <counts group_id="E1" events="4" subjects_affected="3" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Generalized muscle weakness</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Nervous system disturbance</sub_title>
                <counts group_id="E1" events="4" subjects_affected="3" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Urinary frequency distrubance</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Sore throat</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Bruising</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Skin and subcutaneous tissue disorder</sub_title>
                <counts group_id="E1" events="15" subjects_affected="8" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Dr. Helen Bronte-Stewart</name_or_title>
      <organization>Stanford University</organization>
      <phone>650-723-6709</phone>
      <email>hbsmovlab@gmail.com</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/NCT02968433
org study id: IRB 38417
nct id: NCT02968433
lead sponsor: 
has dmc: Yes
The purpose of this study is to demonstrate that young plasma infusions can be performed
      safely in patients with Parkinson's Disease (PD). Secondary outcomes will include behavioral
      and laboratory data that will support the next study that will inquire whether young plasma
      infusions improve or slow the progression of cognitive, mood and/or motor impairment and rate
      markers of the disease.
Parkinson's disease (PD) is a neurodegenerative disease that affects over 1.6 million people
      in the United States and whose incidence increases with age, affecting over 1% of people over
      the age of 65. The neuropathological processes involved in PD are widespread throughout the
      brain, and are reflected in a constellation of motor, cognitive, mood and other non-motor
      symptoms. Treatments to date have largely focused on dopamine replacement strategies or deep
      brain stimulation, both symptomatic treatments.

      As neurodegenerative diseases progress, there are major changes throughout the body and
      brain. These changes are transmitted in the body via the circulatory system between organs,
      tissues and cells. Recent findings from multiple laboratories have shown that infusions of
      young plasma into aging rodents can have beneficial effects on cognitive functions. This
      suggests that the circulating components of plasma can improve cognitive and disease-relevant
      symptoms. This has motivated the field to treat multiple disorders with blood products and
      their constituent active components.

      The established safety of blood transfusions allows the investigators to test whether
      infusions of young plasma can ease the neurological symptoms in human subjects with
      neurodegenerative diseases. A related study of plasma infusions has already been completed at
      Stanford in patients with Alzheimer's disease (ClinicalTrials.gov identifier NCT02256306).

      The investigator proposes to test the safety and efficacy of transfusing young plasma into PD
      participants, in order to establish its effects on motor and cognitive functions in
      participants in a Phase 1 study. The successful completion of this study will inform the
      design of future, larger and multicenter studies with the goal to determine whether infusions
      of young plasma can ameliorate the neurodegenerative symptoms and underlying pathophysiology
      in Parkinson's disease.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of Related and Unrelated Adverse Events
time frame: 8 weeks
description: The primary outcome measure is the number of adverse events across all participants that might be related to young plasma infusions as a novel treatment to Parkinson's Disease symptoms. Adverse events were categorized as probably, possibly, or not related to the study intervention.
measure: Change in Quantitative Data of Cognitive Ability (Neuropsychological Battery)
time frame: 8 weeks
description: Change in quantitative data of cognitive ability. Raw scores and normative scores were calculated for all measures according to standardized procedures across all 3 time points.
The cognitive test battery included:
Trail Making Test Part A (0-92; lower scores indicate better performance) and B (0-300; lower scores indicate better performance)
Digit Symbol Modalities Test (Oral: 0-110 and Written: 0-110; higher scores indicate better performance)
Animal Naming Test (0-no maximum; higher scores indicate better performance)
Controlled Oral Word Association Test (COWAT) (0-no maximum; higher score indicates better performance)
CogStateTM Groton Maze Learning Test (GML) (minimum score is 0; lower scores indicate better performance)
Wechsler Abbreviated Scale of Intelligence-II (WASI-II) Block Design (0-71; higher scores indicate better performance) and Matrix Reasoning (0-30; higher scores indicate better performance)
measure: Change in Quality of Life
time frame: 8 weeks
description: Quality of life (QOL) changes were tracked using the self-report Parkinson's Disease Questionnaire-39 (PDQ-39). The PDQ-39 includes 8 sub-scales: Mobility (raw score range 0-40), Activities of Daily Living (raw score range 0-24), Emotional Well-Being (raw score range 0-24), Stigma (raw score range 0-16), Social Support (raw score range 0-12), Cognition (raw score range 0-16), Communication (raw score range 0-12), and Bodily Discomfort (raw score range 0-12). Subscales scores are totaled then converted to a percentage to calculate the Total score (0 to 100, higher scores indicating the more problems). Ratings are based on participant experiences over the course of the prior month. Lower scores represent better quality of life for all scores.
measure: Change in Quantitative Data of Motor Movements up to 8 Weeks
time frame: 8 weeks
description: The second outcome measure is the change in the quantitative data of current motor movement ability.
Patients completed a repetitive Wrist Flexion Extension (rWFE) task with both hands, off therapy at the baseline, immediate-post, and delayed-post visits. Patients were instructed to flex and extend their hands at the wrist as quickly as possible after a "Go" command was given and to stop when instructed. This movement was self-paced, lasted 30 seconds, and was measured using wearable sensors attached to the dorsum of each hand (Motus Bioengineering, Inc.). Variables of interest included the mean angular velocity (Vrms), the variability of mean angular velocity, (CV Vrms), and rhythmicity, defined as the regularity of the interstrike interval (CV ISI). MA = more affected; LA = less affected.
arm group label: Infusions of Young Plasma
arm group type: Experimental
description: All participants will undergo neuropsychological, neuropsychiatric, and kinematic assessments prior to receiving infusions of young plasma as the treatment.
Participants will receive 1 unit of young plasma, twice a week over a four week duration.
After the four weeks of plasma infusions, participants will undergo neuropsychological, neuropsychiatric and kinematic reassessments. No deception will be used.
intervention type: Drug
intervention name: Infusions of young plasma
description: Participants will receive four twice- weekly infusions of 1 unit young plasma (male, ages between 18-25)
arm group label: Infusions of Young Plasma
criteria: 
gender: All
minimum age: 50 Years
maximum age: 80 Years
healthy volunteers: No
last name: Helen Bronte-Stewart, MS, MD
role: Principal Investigator
affiliation: Stanford University
facility: 
country: United States
citation: Sha SJ, Deutsch GK, Tian L, Richardson K, Coburn M, Gaudioso JL, Marcal T, Solomon E, Boumis A, Bet A, Mennes M, van Oort E, Beckmann CF, Braithwaite SP, Jackson S, Nikolich K, Stephens D, Kerchner GA, Wyss-Coray T. Safety, Tolerability, and Feasibility of Young Plasma Infusion in the Plasma for Alzheimer Symptom Amelioration Study: A Randomized Clinical Trial. JAMA Neurol. 2019 Jan 1;76(1):35-40. doi: 10.1001/jamaneurol.2018.3288.
PMID: 30383097
citation: Villeda SA, Luo J, Mosher KI, Zou B, Britschgi M, Bieri G, Stan TM, Fainberg N, Ding Z, Eggel A, Lucin KM, Czirr E, Park JS, Couillard-Despres S, Aigner L, Li G, Peskind ER, Kaye JA, Quinn JF, Galasko DR, Xie XS, Rando TA, Wyss-Coray T. The ageing systemic milieu negatively regulates neurogenesis and cognitive function. Nature. 2011 Aug 31;477(7362):90-4. doi: 10.1038/nature10357.
PMID: 21886162
citation: Villeda SA, Plambeck KE, Middeldorp J, Castellano JM, Mosher KI, Luo J, Smith LK, Bieri G, Lin K, Berdnik D, Wabl R, Udeochu J, Wheatley EG, Zou B, Simmons DA, Xie XS, Longo FM, Wyss-Coray T. Young blood reverses age-related impairments in cognitive function and synaptic plasticity in mice. Nat Med. 2014 Jun;20(6):659-63. doi: 10.1038/nm.3569. Epub 2014 May 4.
PMID: 24793238
citation: Parker JE, Martinez A, Deutsch GK, Prabhakar V, Lising M, Kapphahn KI, Anidi CM, Neuville R, Coburn M, Shah N, Bronte-Stewart HM. Safety of Plasma Infusions in Parkinson's Disease. Mov Disord. 2020 Nov;35(11):1905-1913. doi: 10.1002/mds.28198. Epub 2020 Jul 7.
PMID: 32633860
responsible party type: Principal Investigator
investigator affiliation: Stanford University
investigator full name: Helen M. Bronte-Stewart
investigator title: Primary Investigator
mesh term: Parkinson Disease
sharing ipd: No
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 