<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/NCT03818737</url>
  </required_header>
  <id_info>
    <org_study_id>IRB00108046</org_study_id>
    <nct_id>NCT03818737</nct_id>
  </id_info>
  <brief_title>Multicenter Trial of Stem Cell Therapy for Osteoarthritis (MILES)</brief_title>
  <acronym>MILES</acronym>
  <official_title>Randomized Multicenter Phase 3 Single-blind Trial Comparing the Efficacy of Corticosteroid Control to Mesenchymal Stem Cell Preparations From Autologous Bone Marrow Concentrate (BMAC), Adipose-derived Stem Cells in the Form of Stromal Vascular Fraction (SVF), and Third-party Human Mesenchymal Stem Cells Manufactured From Umbilical Cord Tissue for the Treatment of Unilateral Knee Osteoarthritis (OA)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Emory University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>The Marcus Foundation</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Emory University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The study is a multicenter trial conducted to compare the effectiveness of an injection of a&#xD;
      corticosteroid control to mesenchymal stem cell (MSC) preparations from autologous bone&#xD;
      marrow concentrate (BMAC), adipose derived stem cells in the form of Stromal Vascular&#xD;
      Fraction (SVF), and third-party human mesenchymal stem cells manufactured from umbilical cord&#xD;
      tissue (UCT) for the treatment of unilateral Knee Osteoarthritis (OA). The study will be&#xD;
      conducted in 4 sites in the United States, and a total of 480 participants will be enrolled&#xD;
      in this study.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Primary osteoarthritis is a debilitating disease characterized by extensive damage to the&#xD;
      joints and excruciating pain leading to loss of activity and depression. Despite advances in&#xD;
      diagnosis and relatively efficient control of nociception, to date, the quest for the&#xD;
      development of a disease modifying osteoarthritis drug has proven unsuccessful. The potential&#xD;
      of mesenchymal stem cells (MSCs) to inhibit inflammation while promoting healing makes them&#xD;
      amenable for the treatment of various ailments ranging from cancer to genetic diseases. In&#xD;
      orthopedic practice, autologous stem cell injections are performed to alleviate the pain&#xD;
      associated with osteoarthritis. A serious gap in knowledge remains whether the currently used&#xD;
      cellular treatments are beneficial in the long term and if one cell therapy outperforms&#xD;
      another.&#xD;
&#xD;
      The most popular form of autologous MSC therapy has been through the use of autologous bone&#xD;
      marrow concentrate (BMAC). The rationale is that when a sample of bone marrow aspirate (BMA)&#xD;
      is collected and the components that are not beneficial to the joint are filtered out (i.e.&#xD;
      red blood cells, neutrophils, etc.) the remaining concentrate (MSCs, platelets, interleukins,&#xD;
      etc) can have a &quot;healing&quot; effect on the environment in which it is injected. However it is&#xD;
      still unknown as to how effective BMAC is for treating orthopedic conditions compared to&#xD;
      other MSC procedures and the most important components of the BMAC mixture that could aid&#xD;
      patients suffering from osteoarthritis.&#xD;
&#xD;
      Adipose tissue has been found to have a large amount of MSCs versus that in bone marrow.&#xD;
      These cells are currently being used in a variety of clinical research studies within the&#xD;
      regenerative medicine field. Through a tissue process which includes washing and&#xD;
      centrifuging, the cellular components can be extracted as a cell pellet, which is also known&#xD;
      as stromal vascular fraction (SVF). Adipose derived SVF is obtained via liposuction, or the&#xD;
      removal of adipose tissue via a suction method.&#xD;
&#xD;
      Although the use of various stem cell preparations for knee osteoarthritis has become&#xD;
      increasingly prevalent, well-designed studies with conclusive proof of comparative&#xD;
      effectiveness and identification of the optimal cell source and &quot;dose&quot; have not been&#xD;
      performed. This study is the first randomized study comparing three types of cellular&#xD;
      treatments to corticosteroids. The main objective of the study is to identify a superior&#xD;
      source of stem cells for the treatment of osteoarthritis and validate its advantages over&#xD;
      corticosteroid injections as the traditional gold standard treatment.&#xD;
&#xD;
      Participants will be randomized study arms with different types of MSCs (bone marrow derived&#xD;
      MSC, adipose derived MSC, and umbilical cord tissue MSC) and then will be further randomized&#xD;
      to receive an injection of the MSC type they were initially assigned to or corticosteroid.&#xD;
      Participants randomized to bone marrow derived MSC or adipose derived MSC will undergo a&#xD;
      procedure (bone marrow aspiration or liposuction). Participants will be blinded to whether&#xD;
      they receive the MSC or corticosteroid injection.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">March 28, 2019</start_date>
  <completion_date type="Actual">May 31, 2022</completion_date>
  <primary_completion_date type="Actual">May 31, 2022</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>The study will include a parallel design using a blocked central randomization scheme of 1:1:1:1. Participants will first be randomized to have MSCs derived from either bone marrow, adipose tissue, or umbilical cord tissue. Then they will be further randomized to receive either an injection of MSCs (from bone marrow, adipose, or umbilical cord tissue, depending on the first randomization) or a corticosteroid injection.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Participant)</masking>
    <masking_description>Participants will not know if they are receiving the MSC or corticosteroid injection.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Change in Visual Analog Pain Scale (VAS-pain) Score</measure>
    <time_frame>Baseline, 1 month, 3 months, 6 months, 9 months, 12 months</time_frame>
    <description>Pain assessment was performed using the Visual Analog Pain Scale (VAS-pain). The VAS-pain is self-completed by the participant. The respondent is asked to place a line perpendicular to the VAS line at the point that represents their pain intensity. Using a ruler, the score is determined by measuring the distance in millimeters (mm) on the line between the &quot;no pain&quot; anchor and the participant's mark, providing a range of scores from 0-100. The recommended cut points for VAS are: no pain (0-4 mm), mild pain (5-44 mm), moderate pain (45-74 mm), and severe pain (75-100 mm). The change in VAS-pain score is the score from the each follow-up visit subtracted from the baseline score. A negative value means that pain has reduced from what it was at baseline.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in Knee Injury and Osteoarthritis Outcome Score (KOOS) - Pain Subscale Score</measure>
    <time_frame>Baseline, 1 month, 3 months, 6 months, 9 months, 12 months</time_frame>
    <description>The KOOS questionnaire assesses the participant's opinion about their osteoarthritis and associated problems. It consists of 5 subscales: pain, symptoms, activities of daily living (ADL) function, sport and recreation function, and knee related quality of life (QoL). The pain subscale has 9 items and response options are given on a 5-point Likert scale where 0 = no problems and 4 = extreme problems. Scores are transformed to a scale ranging from 0 to 100 with 0 indicating extreme symptoms and 100 indicating no symptoms. The change in KOOS-pain subscale score is the score from each follow-up visit subtracted from the baseline score. A negative value means that pain has worsened from what it was at baseline, while a positive value means that pain has improved from baseline.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in Knee Injury and Osteoarthritis Outcome Score (KOOS) - Total Score</measure>
    <time_frame>Baseline, 1 month, 3 months, 6 months, 9 months, 12 months</time_frame>
    <description>The KOOS questionnaire assesses the participant's opinion about their osteoarthritis and associated problems. It consists of 5 subscales: pain, symptoms, activities of daily living (ADL) function, sport and recreation function, and knee related quality of life (QoL). The KOOS has 42 items across all subscales and response options are given on a 5-point Likert scale where 0 = no problems and 4 = extreme problems. The sum of subscale scores is transformed to a scale ranging from 0 to 100 with 0 indicating extreme symptoms and 100 indicating no symptoms. A negative value means that pain has worsened from what it was at baseline, while a positive value means that pain has improved from baseline.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in EuroQuality of Life (EQ-5D-3L) Index Score</measure>
    <time_frame>Baseline, 1 month, 3 months, 6 months, 9 months, 12 months</time_frame>
    <description>The EQ-5D-3L survey measures the severity of five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. The participants will be asked to answer questions regarding these measures and to indicate their current experience on a scale from 1 to 3 (1 being &quot;no problem&quot; and 3 being &quot;most extreme problem&quot;). A sixth item asks participants to rate their current heath from 0 (worst imaginable) to 100 (best imaginable). The answers to these questions are converted into an index value based on the country respondents live in. Health state index scores typically range from less than 0 to 1, where 0 is a health state equivalent to death and 1 is perfect health. Positive values for the change from baseline score indicate improved health.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patient-Reported Outcomes Measurement Information System (PROMIS-29) Score</measure>
    <time_frame>Baseline, 1 month, 3 months, 6 months, 9 months, 12 months</time_frame>
    <description>The PROMIS-29 assesses seven health domains: physical function, anxiety, depression, fatigue, sleep disturbance, pain interference, and ability to participate in social roles and activities. Each of the seven domains has four questions which are scored on a five-point Likert scale. The PROMIS-29 scales are scored using a T-score metric method available at the Assessment Center website (http://assessmentcenter.net). A score of 50 points represents the population average for each scale, and 10 points represent one standard deviation. Scores higher than 50 indicate more of the specific scale's construct, which may indicate a desirable or an undesirable outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall MRI Grade of Osteoarthritis</measure>
    <time_frame>Baseline, Month 6, Month 12</time_frame>
    <description>An MRI grade of osteoarthritis was calculated by rating features viewed by MRI (such as cartilage loss) in terms of severity and extent. Total scores range from 0 to 69 with higher values indicating more severe osteoarthritis.</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">475</enrollment>
  <condition>Osteoarthritis</condition>
  <arm_group>
    <arm_group_label>Bone Marrow Derived MSCs</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants randomized to this arm will undergo bone marrow aspiration and then will be further randomized to receive a standard orthobiologic injection into the knee joint of autologous bone marrow concentrate (BMAC).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Adipose-derived MSCs</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants randomized to this arm will undergo small volume lipoplasty, and then will be further randomized to receive an injection into the knee joint of adipose-derived stromal vascular fraction (SVF).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Umbilical Cord Tissue (UCT) MSCs</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants randomized to this arm will receive an injection into the knee joint of cryopreserved doses of umbilical cord tissue MSCs.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Corticosteroid Injection</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Participants randomized to the bone marrow derived MSC, adipose-derived MSC, or umbilical cord tissue MSC study arms will be further randomized within the arm in a 3:1 ratio to receive either MSCs derived from the study arm of the initial randomization or a corticosteroid (CS) injection. Participants randomized to the control group will receive an injection of corticosteroid into the knee joint.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Bone Marrow Derived MSCs</intervention_name>
    <description>Autologous bone marrow concentrate (BMAC) is a standard orthobiologic injection for knee osteoarthritis. The procedure involves harvesting of bone marrow aspirate (BMA) from the posterior superior iliac spine (PSIS) and then following centrifugation in an FDA approved device (EmCyte GenesisCS Pure BMAC®-60 ml) will be injected back into the knee joint. All injections will be made via ultrasound guidance using a standard approach.</description>
    <arm_group_label>Bone Marrow Derived MSCs</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Adipose-derived MSCs</intervention_name>
    <description>Adipose-derived Stromal Vascular Fraction (SVF) will be obtained from a mini lipoaspirate. The lipoaspirate will then be enzymatically digested to produce a SVF that will be injected into the knee joint. All injections will be made via ultrasound guidance using a standard approach.</description>
    <arm_group_label>Adipose-derived MSCs</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Umbilical Cord Tissue (UCT) MSCs</intervention_name>
    <description>Cryopreserved doses of umbilical cord tissue MSCs will be used. These MSCs were cryopreserved at P2 culture in plasmalyte A + 5% human serum albumin in 5 finger cryobags containing 20 million cells in 4 mL and stored under liquid nitrogen until shipment. Cells will be transported in a dry shipper and thawed at the study sites. The dose of MSCs will be aspirated from the cryobag into a sterile syringe and directly injected into the knee. All injections will be made via ultrasound guidance using a standard approach.</description>
    <arm_group_label>Umbilical Cord Tissue (UCT) MSCs</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Corticosteroid injection</intervention_name>
    <description>The corticosteroid injection is prepared by mixing 1cc of 40mg/dL depomedrol and 6cc of normal saline in a 10cc syringe will be made into the knee joint. All injections will be made via ultrasound guidance using a standard approach.</description>
    <arm_group_label>Corticosteroid Injection</arm_group_label>
    <other_name>Depo-Medrol</other_name>
    <other_name>Methylprednisolone</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age greater or equal to 40 but less than or equal to 70 years old&#xD;
&#xD;
          -  Males and females&#xD;
&#xD;
          -  Recent knee radiograph of the targeted knee (standing anteroposterior (AP) lateral and&#xD;
             sunrise view)&#xD;
&#xD;
          -  Diagnosis of OA in the targeted knee (radiographic evidence of OA in the medial and/or&#xD;
             lateral tibiofemoral compartment, which would include one or more osteophytes on a&#xD;
             standard radiograph taken within 3 months)&#xD;
&#xD;
          -  Continued OA pain in the targeted knee despite conservative measures (per treating&#xD;
             provider's discretion)&#xD;
&#xD;
          -  Average daily Visual Analog Scale (VAS) ≥3&#xD;
&#xD;
          -  Kellgren-Lawrence system of Grade II, III, or IV&#xD;
&#xD;
          -  Subjects may have concomitant patellofemoral but they must have stage II or higher&#xD;
             generalized knee OA&#xD;
&#xD;
          -  Females of childbearing potential only, must have a negative pregnancy test done at&#xD;
             screening prior to enrollment in the study&#xD;
&#xD;
          -  Women and men of child-producing potential must agree to use acceptable contraception&#xD;
             methods for the duration of the trial such as birth control pills or condoms with&#xD;
             spermicide&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Clinically apparent tense effusion of the targeted knee&#xD;
&#xD;
          -  Significant valgus/varus deformities (+/- 10 degrees)&#xD;
&#xD;
          -  Viscosupplementation within 6 months in the targeted knee&#xD;
&#xD;
          -  Other biologic injection (PRP or stem cell) within 1 year in the targeted knee&#xD;
&#xD;
          -  Surgery in the targeted knee within the past 6 months (either open or scope)&#xD;
&#xD;
          -  Systemic or intra-articular injection of corticosteroids in any joint within 3 months&#xD;
             before screening&#xD;
&#xD;
          -  Daily opioid use for the past three months&#xD;
&#xD;
          -  History of malignancy in the previous 5 years prior to study entry, with the exception&#xD;
             of in-situ cancers treated only by local excision with curative intent&#xD;
&#xD;
          -  History of, or ongoing, autoimmune disorder that requires treatment with an&#xD;
             immunosuppressive medication&#xD;
&#xD;
          -  Active, suspected, or prior infection to the joint in the targeted knee&#xD;
&#xD;
          -  Part of a vulnerable population per Office for Human Research Protections (OHRP)&#xD;
             definition (pregnant women and breast-feeding women, cognitively impaired, prisoners,&#xD;
             etc.)&#xD;
&#xD;
          -  Unwilling to discontinue the use of Non-Steroidal Anti-Inflammatory (NSAID)s for 7&#xD;
             calendar days prior to the procedure&#xD;
&#xD;
          -  Unwilling to discontinue use of NSAIDS for 5 calendar days after procedure&#xD;
&#xD;
          -  History of bleeding disorders or inflammatory joint disease&#xD;
&#xD;
          -  Inability to hold anti-platelet therapy according to treating provider prior to&#xD;
             procedure&#xD;
&#xD;
          -  Subject is, in the opinion of the investigator, unable to comply with the requirements&#xD;
             of the study protocol or is unsuitable for the study for any reason&#xD;
&#xD;
          -  Uncontrolled diabetes&#xD;
&#xD;
          -  Subject has an active workers' compensation case in progress with targeted knee&#xD;
&#xD;
          -  Subject with insufficient amount of subcutaneous tissue&#xD;
&#xD;
          -  Hemoglobin less than 10g/dL at the time of screening&#xD;
&#xD;
          -  Leukocytes &lt;3,000/μL; neutrophils &lt;1,500/μL; lymphocytes &lt;800/μL; platelets&#xD;
             &lt;100,000/μL at the time of screening&#xD;
&#xD;
          -  Diagnosis of liver disease as defined by alanine aminotransferase (ALT) &gt;3x the upper&#xD;
             limit of age-determined normal (ULN) or total bilirubin &gt; 1.5x ULN&#xD;
&#xD;
          -  Subjects who have had greater than 3 corticosteroid injections in the targeted knee in&#xD;
             the 12 months prior to screening or at the physician's discretion&#xD;
&#xD;
          -  Subjects with a known diagnosis of osteoporosis&#xD;
&#xD;
          -  Subjects with anticipated use of systemic corticosteroids during the study period for&#xD;
             treatment of a chronic medical condition&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>40 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Hicham Drissi, PhD</last_name>
    <role>Study Director</role>
    <affiliation>Emory University</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Scott D Boden, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Emory University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Andrews Institute</name>
      <address>
        <city>Gulf Breeze</city>
        <state>Florida</state>
        <zip>32561</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Emory Clinic</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30322</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Duke University</name>
      <address>
        <city>Durham</city>
        <state>North Carolina</state>
        <zip>27710</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sanford Health</name>
      <address>
        <city>Fargo</city>
        <state>North Dakota</state>
        <zip>58103</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sanford Health</name>
      <address>
        <city>Sioux Falls</city>
        <state>South Dakota</state>
        <zip>57104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>July 2023</verification_date>
  <study_first_submitted>January 24, 2019</study_first_submitted>
  <study_first_submitted_qc>January 24, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 28, 2019</study_first_posted>
  <results_first_submitted>May 27, 2023</results_first_submitted>
  <results_first_submitted_qc>July 25, 2023</results_first_submitted_qc>
  <results_first_posted type="Actual">July 27, 2023</results_first_posted>
  <last_update_submitted>July 25, 2023</last_update_submitted>
  <last_update_submitted_qc>July 25, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">July 27, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Emory University</investigator_affiliation>
    <investigator_full_name>Scott D Boden</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <keyword>mesenchymal stem cells</keyword>
  <keyword>corticosteroids</keyword>
  <keyword>bone marrow aspiration</keyword>
  <keyword>adipose-derived stromal vascular fraction</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Osteoarthritis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Methylprednisolone</mesh_term>
    <mesh_term>Methylprednisolone Acetate</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>October 22, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/37/NCT03818737/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Participants were recruited from Duke University in Durham, North Carolina, Sanford Health in Fargo, North Dakota, The Emory Clinic in Atlanta, Georgia, Sanford Health in Sioux Falls, South Dakota, and the Andrews Institute in Gulf Breeze, Florida, USA. Participant enrollment began March 28, 2019 and all follow-up was complete by May 31, 2022.</recruitment_details>
      <group_list>
        <group group_id="P1">
          <title>Bone Marrow Derived Mesenchymal Stem Cells (MSCs)</title>
          <description>Participants randomized to this arm underwent bone marrow aspiration and then were further randomized to receive a standard orthobiologic injection into the knee joint of autologous bone marrow concentrate (BMAC).</description>
        </group>
        <group group_id="P2">
          <title>Adipose-derived MSCs</title>
          <description>Participants randomized to this arm underwent small volume lipoplasty, and then were further randomized to receive an injection into the knee joint of adipose-derived stromal vascular fraction (SVF).</description>
        </group>
        <group group_id="P3">
          <title>Umbilical Cord Tissue (UCT) MSCs</title>
          <description>Participants randomized to this arm received an injection into the knee joint of cryopreserved doses of umbilical cord tissue MSCs.</description>
        </group>
        <group group_id="P4">
          <title>Corticosteroid Injection</title>
          <description>Participants randomized to the bone marrow derived MSCs, adipose-derived MSCs, or umbilical cord tissue MSCs study arms who were further randomized to the control group and received a corticosteroid (CS) injection into the knee joint.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="118"/>
                <participants group_id="P2" count="119"/>
                <participants group_id="P3" count="118"/>
                <participants group_id="P4" count="120"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Received Study Intervention</title>
              <participants_list>
                <participants group_id="P1" count="107"/>
                <participants group_id="P2" count="109"/>
                <participants group_id="P3" count="116"/>
                <participants group_id="P4" count="108"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="97"/>
                <participants group_id="P2" count="93"/>
                <participants group_id="P3" count="103"/>
                <participants group_id="P4" count="97"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="21"/>
                <participants group_id="P2" count="26"/>
                <participants group_id="P3" count="15"/>
                <participants group_id="P4" count="23"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Bone Marrow Derived MSCs</title>
          <description>Participants randomized to this arm underwent bone marrow aspiration and then were further randomized to receive a standard orthobiologic injection into the knee joint of autologous bone marrow concentrate (BMAC).</description>
        </group>
        <group group_id="B2">
          <title>Adipose-derived MSCs</title>
          <description>Participants randomized to this arm underwent small volume lipoplasty, and then were further randomized to receive an injection into the knee joint of adipose-derived stromal vascular fraction (SVF).</description>
        </group>
        <group group_id="B3">
          <title>Umbilical Cord Tissue (UCT) MSCs</title>
          <description>Participants randomized to this arm received an injection into the knee joint of cryopreserved doses of umbilical cord tissue MSCs.</description>
        </group>
        <group group_id="B4">
          <title>Corticosteroid Injection</title>
          <description>Participants randomized to the bone marrow derived MSC, adipose-derived MSC, or umbilical cord tissue MSC study arms who were further randomized to the control group and received a corticosteroid (CS) injection into the knee joint.</description>
        </group>
        <group group_id="B5">
          <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="118"/>
            <count group_id="B2" value="119"/>
            <count group_id="B3" value="118"/>
            <count group_id="B4" value="120"/>
            <count group_id="B5" value="475"/>
          </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="58.6" spread="7.33"/>
                    <measurement group_id="B2" value="58.2" spread="7.31"/>
                    <measurement group_id="B3" value="57.9" spread="8.18"/>
                    <measurement group_id="B4" value="58.3" spread="8.05"/>
                    <measurement group_id="B5" value="58.3" spread="7.71"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Categorical age</title>
              <category_list>
                <category>
                  <title>40 to 59 years of age</title>
                  <measurement_list>
                    <measurement group_id="B1" value="57"/>
                    <measurement group_id="B2" value="63"/>
                    <measurement group_id="B3" value="64"/>
                    <measurement group_id="B4" value="62"/>
                    <measurement group_id="B5" value="246"/>
                  </measurement_list>
                </category>
                <category>
                  <title>60 to 70 years of age</title>
                  <measurement_list>
                    <measurement group_id="B1" value="61"/>
                    <measurement group_id="B2" value="56"/>
                    <measurement group_id="B3" value="54"/>
                    <measurement group_id="B4" value="58"/>
                    <measurement group_id="B5" value="229"/>
                  </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="62"/>
                    <measurement group_id="B2" value="63"/>
                    <measurement group_id="B3" value="65"/>
                    <measurement group_id="B4" value="71"/>
                    <measurement group_id="B5" value="261"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="56"/>
                    <measurement group_id="B2" value="56"/>
                    <measurement group_id="B3" value="53"/>
                    <measurement group_id="B4" value="49"/>
                    <measurement group_id="B5" value="214"/>
                  </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="5"/>
                    <measurement group_id="B3" value="5"/>
                    <measurement group_id="B4" value="6"/>
                    <measurement group_id="B5" value="16"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="116"/>
                    <measurement group_id="B2" value="113"/>
                    <measurement group_id="B3" value="113"/>
                    <measurement group_id="B4" value="114"/>
                    <measurement group_id="B5" value="456"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="3"/>
                  </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="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="4"/>
                    <measurement group_id="B4" value="2"/>
                    <measurement group_id="B5" value="13"/>
                  </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 group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="19"/>
                    <measurement group_id="B2" value="15"/>
                    <measurement group_id="B3" value="11"/>
                    <measurement group_id="B4" value="12"/>
                    <measurement group_id="B5" value="57"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="92"/>
                    <measurement group_id="B2" value="99"/>
                    <measurement group_id="B3" value="102"/>
                    <measurement group_id="B4" value="104"/>
                    <measurement group_id="B5" value="397"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="2"/>
                    <measurement group_id="B5" value="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" 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="118"/>
                    <measurement group_id="B2" value="119"/>
                    <measurement group_id="B3" value="118"/>
                    <measurement group_id="B4" value="120"/>
                    <measurement group_id="B5" value="475"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change in Visual Analog Pain Scale (VAS-pain) Score</title>
        <description>Pain assessment was performed using the Visual Analog Pain Scale (VAS-pain). The VAS-pain is self-completed by the participant. The respondent is asked to place a line perpendicular to the VAS line at the point that represents their pain intensity. Using a ruler, the score is determined by measuring the distance in millimeters (mm) on the line between the &quot;no pain&quot; anchor and the participant's mark, providing a range of scores from 0-100. The recommended cut points for VAS are: no pain (0-4 mm), mild pain (5-44 mm), moderate pain (45-74 mm), and severe pain (75-100 mm). The change in VAS-pain score is the score from the each follow-up visit subtracted from the baseline score. A negative value means that pain has reduced from what it was at baseline.</description>
        <time_frame>Baseline, 1 month, 3 months, 6 months, 9 months, 12 months</time_frame>
        <population>This analysis includes participants who successfully completed this assessment at the indicated post-baseline study visit. Some participants withdrew from the study prior to study completion and some attended study visits but did not complete each study assessment correctly.</population>
        <group_list>
          <group group_id="O1">
            <title>Bone Marrow Derived MSCs</title>
            <description>Participants randomized to this arm underwent bone marrow aspiration and then were further randomized to receive a standard orthobiologic injection into the knee joint of autologous bone marrow concentrate (BMAC).</description>
          </group>
          <group group_id="O2">
            <title>Adipose-derived MSCs</title>
            <description>Participants randomized to this arm underwent small volume lipoplasty, and then were further randomized to receive an injection into the knee joint of adipose-derived stromal vascular fraction (SVF).</description>
          </group>
          <group group_id="O3">
            <title>Umbilical Cord Tissue (UCT) MSCs</title>
            <description>Participants randomized to this arm received an injection into the knee joint of cryopreserved doses of umbilical cord tissue MSCs.</description>
          </group>
          <group group_id="O4">
            <title>Corticosteroid Injection</title>
            <description>Participants randomized to the bone marrow derived MSC, adipose-derived MSC, or umbilical cord tissue MSC study arms who were further randomized to the control group and received a corticosteroid (CS) injection into the knee joint.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Visual Analog Pain Scale (VAS-pain) Score</title>
          <description>Pain assessment was performed using the Visual Analog Pain Scale (VAS-pain). The VAS-pain is self-completed by the participant. The respondent is asked to place a line perpendicular to the VAS line at the point that represents their pain intensity. Using a ruler, the score is determined by measuring the distance in millimeters (mm) on the line between the &quot;no pain&quot; anchor and the participant's mark, providing a range of scores from 0-100. The recommended cut points for VAS are: no pain (0-4 mm), mild pain (5-44 mm), moderate pain (45-74 mm), and severe pain (75-100 mm). The change in VAS-pain score is the score from the each follow-up visit subtracted from the baseline score. A negative value means that pain has reduced from what it was at baseline.</description>
          <population>This analysis includes participants who successfully completed this assessment at the indicated post-baseline study visit. Some participants withdrew from the study prior to study completion and some attended study visits but did not complete each study assessment correctly.</population>
          <units>units on a scale</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="101"/>
                <count group_id="O2" value="102"/>
                <count group_id="O3" value="111"/>
                <count group_id="O4" value="101"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Absolute Change from Baseline at Month 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="101"/>
                    <count group_id="O2" value="101"/>
                    <count group_id="O3" value="111"/>
                    <count group_id="O4" value="101"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-20.2" spread="2.52"/>
                    <measurement group_id="O2" value="-15.9" spread="2.48"/>
                    <measurement group_id="O3" value="-16.7" spread="2.40"/>
                    <measurement group_id="O4" value="-25.2" spread="2.49"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Absolute Change from Baseline at Month 3</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="98"/>
                    <count group_id="O2" value="102"/>
                    <count group_id="O3" value="105"/>
                    <count group_id="O4" value="101"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-28.8" spread="2.54"/>
                    <measurement group_id="O2" value="-17.8" spread="2.48"/>
                    <measurement group_id="O3" value="-17.3" spread="2.43"/>
                    <measurement group_id="O4" value="-21.1" spread="2.49"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Absolute Change from Baseline at Month 6</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="94"/>
                    <count group_id="O2" value="94"/>
                    <count group_id="O3" value="99"/>
                    <count group_id="O4" value="97"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-23.2" spread="2.56"/>
                    <measurement group_id="O2" value="-21.6" spread="2.53"/>
                    <measurement group_id="O3" value="-19.7" spread="2.47"/>
                    <measurement group_id="O4" value="-22.7" spread="2.51"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Absolute Change from Baseline at Month 9</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="83"/>
                    <count group_id="O2" value="81"/>
                    <count group_id="O3" value="83"/>
                    <count group_id="O4" value="81"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-21.9" spread="2.64"/>
                    <measurement group_id="O2" value="-17.9" spread="2.63"/>
                    <measurement group_id="O3" value="-16.5" spread="2.58"/>
                    <measurement group_id="O4" value="-23.3" spread="2.63"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Absolute Change from Baseline at Month 12</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="95"/>
                    <count group_id="O2" value="91"/>
                    <count group_id="O3" value="98"/>
                    <count group_id="O4" value="97"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-25.5" spread="2.56"/>
                    <measurement group_id="O2" value="-19.9" spread="2.55"/>
                    <measurement group_id="O3" value="-20.6" spread="2.48"/>
                    <measurement group_id="O4" value="-22.3" spread="2.51"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Change in Knee Injury and Osteoarthritis Outcome Score (KOOS) - Pain Subscale Score</title>
        <description>The KOOS questionnaire assesses the participant's opinion about their osteoarthritis and associated problems. It consists of 5 subscales: pain, symptoms, activities of daily living (ADL) function, sport and recreation function, and knee related quality of life (QoL). The pain subscale has 9 items and response options are given on a 5-point Likert scale where 0 = no problems and 4 = extreme problems. Scores are transformed to a scale ranging from 0 to 100 with 0 indicating extreme symptoms and 100 indicating no symptoms. The change in KOOS-pain subscale score is the score from each follow-up visit subtracted from the baseline score. A negative value means that pain has worsened from what it was at baseline, while a positive value means that pain has improved from baseline.</description>
        <time_frame>Baseline, 1 month, 3 months, 6 months, 9 months, 12 months</time_frame>
        <population>This analysis includes participants who successfully completed this assessment at the indicated post-baseline study visit. Some participants withdrew from the study prior to study completion and some attended study visits but did not complete each study assessment correctly.</population>
        <group_list>
          <group group_id="O1">
            <title>Bone Marrow Derived MSCs</title>
            <description>Participants randomized to this arm underwent bone marrow aspiration and then were further randomized to receive a standard orthobiologic injection into the knee joint of autologous bone marrow concentrate (BMAC).</description>
          </group>
          <group group_id="O2">
            <title>Adipose-derived MSCs</title>
            <description>Participants randomized to this arm underwent small volume lipoplasty, and then were further randomized to receive an injection into the knee joint of adipose-derived stromal vascular fraction (SVF).</description>
          </group>
          <group group_id="O3">
            <title>Umbilical Cord Tissue (UCT) MSCs</title>
            <description>Participants randomized to this arm received an injection into the knee joint of cryopreserved doses of umbilical cord tissue MSCs.</description>
          </group>
          <group group_id="O4">
            <title>Corticosteroid Injection</title>
            <description>Participants randomized to the bone marrow derived MSC, adipose-derived MSC, or umbilical cord tissue MSC study arms who were further randomized to the control group and received a corticosteroid (CS) injection into the knee joint.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Knee Injury and Osteoarthritis Outcome Score (KOOS) - Pain Subscale Score</title>
          <description>The KOOS questionnaire assesses the participant's opinion about their osteoarthritis and associated problems. It consists of 5 subscales: pain, symptoms, activities of daily living (ADL) function, sport and recreation function, and knee related quality of life (QoL). The pain subscale has 9 items and response options are given on a 5-point Likert scale where 0 = no problems and 4 = extreme problems. Scores are transformed to a scale ranging from 0 to 100 with 0 indicating extreme symptoms and 100 indicating no symptoms. The change in KOOS-pain subscale score is the score from each follow-up visit subtracted from the baseline score. A negative value means that pain has worsened from what it was at baseline, while a positive value means that pain has improved from baseline.</description>
          <population>This analysis includes participants who successfully completed this assessment at the indicated post-baseline study visit. Some participants withdrew from the study prior to study completion and some attended study visits but did not complete each study assessment correctly.</population>
          <units>score on a scale</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="101"/>
                <count group_id="O2" value="101"/>
                <count group_id="O3" value="111"/>
                <count group_id="O4" value="101"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Absolute Change from Baseline at Month 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="101"/>
                    <count group_id="O2" value="100"/>
                    <count group_id="O3" value="111"/>
                    <count group_id="O4" value="101"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="15.5" spread="1.85"/>
                    <measurement group_id="O2" value="15.4" spread="1.84"/>
                    <measurement group_id="O3" value="11.5" spread="1.77"/>
                    <measurement group_id="O4" value="19.2" spread="1.83"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Absolute Change from Baseline at Month 3</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="99"/>
                    <count group_id="O2" value="101"/>
                    <count group_id="O3" value="105"/>
                    <count group_id="O4" value="101"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="19.2" spread="1.86"/>
                    <measurement group_id="O2" value="16.8" spread="1.84"/>
                    <measurement group_id="O3" value="12.8" spread="1.79"/>
                    <measurement group_id="O4" value="18.7" spread="1.83"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Absolute Change from Baseline at Month 6</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="94"/>
                    <count group_id="O2" value="93"/>
                    <count group_id="O3" value="99"/>
                    <count group_id="O4" value="97"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="18.1" spread="1.88"/>
                    <measurement group_id="O2" value="17.2" spread="1.87"/>
                    <measurement group_id="O3" value="15.4" spread="1.81"/>
                    <measurement group_id="O4" value="18.6" spread="1.85"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Absolute Change from Baseline at Month 9</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="83"/>
                    <count group_id="O2" value="80"/>
                    <count group_id="O3" value="83"/>
                    <count group_id="O4" value="81"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="16.2" spread="193"/>
                    <measurement group_id="O2" value="14.7" spread="1.93"/>
                    <measurement group_id="O3" value="13.9" spread="1.88"/>
                    <measurement group_id="O4" value="16.3" spread="1.92"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Absolute Change from Baseline at Month 12</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="95"/>
                    <count group_id="O2" value="92"/>
                    <count group_id="O3" value="98"/>
                    <count group_id="O4" value="96"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="18.9" spread="1.88"/>
                    <measurement group_id="O2" value="17.3" spread="1.88"/>
                    <measurement group_id="O3" value="16.4" spread="1.81"/>
                    <measurement group_id="O4" value="18.5" spread="1.85"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Knee Injury and Osteoarthritis Outcome Score (KOOS) - Total Score</title>
        <description>The KOOS questionnaire assesses the participant's opinion about their osteoarthritis and associated problems. It consists of 5 subscales: pain, symptoms, activities of daily living (ADL) function, sport and recreation function, and knee related quality of life (QoL). The KOOS has 42 items across all subscales and response options are given on a 5-point Likert scale where 0 = no problems and 4 = extreme problems. The sum of subscale scores is transformed to a scale ranging from 0 to 100 with 0 indicating extreme symptoms and 100 indicating no symptoms. A negative value means that pain has worsened from what it was at baseline, while a positive value means that pain has improved from baseline.</description>
        <time_frame>Baseline, 1 month, 3 months, 6 months, 9 months, 12 months</time_frame>
        <population>This analysis includes participants who successfully completed this assessment at the indicated post-baseline study visit. Some participants withdrew from the study prior to study completion and some attended study visits but did not complete each study assessment correctly. This analysis includes participants who had complete information for each subscale of the KOOS questionnaire, allowing for calculation of the total KOOS score.</population>
        <group_list>
          <group group_id="O1">
            <title>Bone Marrow Derived MSCs</title>
            <description>Participants randomized to this arm underwent bone marrow aspiration and then were further randomized to receive a standard orthobiologic injection into the knee joint of autologous bone marrow concentrate (BMAC).</description>
          </group>
          <group group_id="O2">
            <title>Adipose-derived MSCs</title>
            <description>Participants randomized to this arm underwent small volume lipoplasty, and then were further randomized to receive an injection into the knee joint of adipose-derived stromal vascular fraction (SVF).</description>
          </group>
          <group group_id="O3">
            <title>Umbilical Cord Tissue (UCT) MSCs</title>
            <description>Participants randomized to this arm received an injection into the knee joint of cryopreserved doses of umbilical cord tissue MSCs.</description>
          </group>
          <group group_id="O4">
            <title>Corticosteroid Injection</title>
            <description>Participants randomized to the bone marrow derived MSC, adipose-derived MSC, or umbilical cord tissue MSC study arms who were further randomized to the control group and received a corticosteroid (CS) injection into the knee joint.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Knee Injury and Osteoarthritis Outcome Score (KOOS) - Total Score</title>
          <description>The KOOS questionnaire assesses the participant's opinion about their osteoarthritis and associated problems. It consists of 5 subscales: pain, symptoms, activities of daily living (ADL) function, sport and recreation function, and knee related quality of life (QoL). The KOOS has 42 items across all subscales and response options are given on a 5-point Likert scale where 0 = no problems and 4 = extreme problems. The sum of subscale scores is transformed to a scale ranging from 0 to 100 with 0 indicating extreme symptoms and 100 indicating no symptoms. A negative value means that pain has worsened from what it was at baseline, while a positive value means that pain has improved from baseline.</description>
          <population>This analysis includes participants who successfully completed this assessment at the indicated post-baseline study visit. Some participants withdrew from the study prior to study completion and some attended study visits but did not complete each study assessment correctly. This analysis includes participants who had complete information for each subscale of the KOOS questionnaire, allowing for calculation of the total KOOS score.</population>
          <units>score 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="100"/>
                <count group_id="O2" value="95"/>
                <count group_id="O3" value="109"/>
                <count group_id="O4" value="101"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Change from Baseline at Month 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="100"/>
                    <count group_id="O2" value="95"/>
                    <count group_id="O3" value="109"/>
                    <count group_id="O4" value="101"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="14.48" spread="14.95"/>
                    <measurement group_id="O2" value="14.34" spread="12.40"/>
                    <measurement group_id="O3" value="11.14" spread="12.47"/>
                    <measurement group_id="O4" value="17.70" spread="14.65"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline at Month 3</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="97"/>
                    <count group_id="O2" value="95"/>
                    <count group_id="O3" value="104"/>
                    <count group_id="O4" value="101"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="18.63" spread="15.32"/>
                    <measurement group_id="O2" value="16.30" spread="16.02"/>
                    <measurement group_id="O3" value="13.85" spread="14.36"/>
                    <measurement group_id="O4" value="17.21" spread="16.97"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline at Month 6</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="91"/>
                    <count group_id="O2" value="88"/>
                    <count group_id="O3" value="96"/>
                    <count group_id="O4" value="97"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="18.39" spread="16.96"/>
                    <measurement group_id="O2" value="17.53" spread="16.23"/>
                    <measurement group_id="O3" value="15.62" spread="14.66"/>
                    <measurement group_id="O4" value="17.44" spread="17.47"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline at Month 9</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="82"/>
                    <count group_id="O2" value="78"/>
                    <count group_id="O3" value="82"/>
                    <count group_id="O4" value="81"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="14.17" spread="18.87"/>
                    <measurement group_id="O2" value="13.36" spread="16.91"/>
                    <measurement group_id="O3" value="13.96" spread="15.83"/>
                    <measurement group_id="O4" value="116.30" spread="18.54"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline at Month 12</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="95"/>
                    <count group_id="O2" value="89"/>
                    <count group_id="O3" value="96"/>
                    <count group_id="O4" value="94"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="18.52" spread="18.93"/>
                    <measurement group_id="O2" value="17.61" spread="19.70"/>
                    <measurement group_id="O3" value="17.49" spread="18.34"/>
                    <measurement group_id="O4" value="19.27" spread="18.54"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in EuroQuality of Life (EQ-5D-3L) Index Score</title>
        <description>The EQ-5D-3L survey measures the severity of five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. The participants will be asked to answer questions regarding these measures and to indicate their current experience on a scale from 1 to 3 (1 being &quot;no problem&quot; and 3 being &quot;most extreme problem&quot;). A sixth item asks participants to rate their current heath from 0 (worst imaginable) to 100 (best imaginable). The answers to these questions are converted into an index value based on the country respondents live in. Health state index scores typically range from less than 0 to 1, where 0 is a health state equivalent to death and 1 is perfect health. Positive values for the change from baseline score indicate improved health.</description>
        <time_frame>Baseline, 1 month, 3 months, 6 months, 9 months, 12 months</time_frame>
        <population>This analysis includes participants who successfully completed this assessment at the indicated post-baseline study visit. Some participants withdrew from the study prior to study completion and some attended study visits but did not complete each study assessment correctly.</population>
        <group_list>
          <group group_id="O1">
            <title>Bone Marrow Derived MSCs</title>
            <description>Participants randomized to this arm underwent bone marrow aspiration and then were further randomized to receive a standard orthobiologic injection into the knee joint of autologous bone marrow concentrate (BMAC).</description>
          </group>
          <group group_id="O2">
            <title>Adipose-derived MSCs</title>
            <description>Participants randomized to this arm underwent small volume lipoplasty, and then were further randomized to receive an injection into the knee joint of adipose-derived stromal vascular fraction (SVF).</description>
          </group>
          <group group_id="O3">
            <title>Umbilical Cord Tissue (UCT) MSCs</title>
            <description>Participants randomized to this arm received an injection into the knee joint of cryopreserved doses of umbilical cord tissue MSCs.</description>
          </group>
          <group group_id="O4">
            <title>Corticosteroid Injection</title>
            <description>Participants randomized to the bone marrow derived MSC, adipose-derived MSC, or umbilical cord tissue MSC study arms who were further randomized to the control group and received a corticosteroid (CS) injection into the knee joint.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in EuroQuality of Life (EQ-5D-3L) Index Score</title>
          <description>The EQ-5D-3L survey measures the severity of five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. The participants will be asked to answer questions regarding these measures and to indicate their current experience on a scale from 1 to 3 (1 being &quot;no problem&quot; and 3 being &quot;most extreme problem&quot;). A sixth item asks participants to rate their current heath from 0 (worst imaginable) to 100 (best imaginable). The answers to these questions are converted into an index value based on the country respondents live in. Health state index scores typically range from less than 0 to 1, where 0 is a health state equivalent to death and 1 is perfect health. Positive values for the change from baseline score indicate improved health.</description>
          <population>This analysis includes participants who successfully completed this assessment at the indicated post-baseline study visit. Some participants withdrew from the study prior to study completion and some attended study visits but did not complete each study assessment correctly.</population>
          <units>score on a scale</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="100"/>
                <count group_id="O2" value="101"/>
                <count group_id="O3" value="111"/>
                <count group_id="O4" value="100"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Absolute Change from Baseline at Month 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="100"/>
                    <count group_id="O2" value="100"/>
                    <count group_id="O3" value="111"/>
                    <count group_id="O4" value="100"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.1" spread="0.01"/>
                    <measurement group_id="O2" value="0.1" spread="0.01"/>
                    <measurement group_id="O3" value="0.1" spread="0.01"/>
                    <measurement group_id="O4" value="0.1" spread="0.01"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Absolute Change from Baseline at Month 3</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="98"/>
                    <count group_id="O2" value="101"/>
                    <count group_id="O3" value="105"/>
                    <count group_id="O4" value="99"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.1" spread="0.01"/>
                    <measurement group_id="O2" value="0.1" spread="0.01"/>
                    <measurement group_id="O3" value="0.1" spread="0.01"/>
                    <measurement group_id="O4" value="0.1" spread="0.01"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Absolute Change from Baseline at Month 6</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="94"/>
                    <count group_id="O2" value="93"/>
                    <count group_id="O3" value="98"/>
                    <count group_id="O4" value="96"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.1" spread="0.01"/>
                    <measurement group_id="O2" value="0.1" spread="0.01"/>
                    <measurement group_id="O3" value="0.1" spread="0.01"/>
                    <measurement group_id="O4" value="0.1" spread="0.01"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Absolute Change from Baseline at Month 9</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="83"/>
                    <count group_id="O2" value="80"/>
                    <count group_id="O3" value="83"/>
                    <count group_id="O4" value="80"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0" spread="0.02"/>
                    <measurement group_id="O2" value="0.1" spread="0.02"/>
                    <measurement group_id="O3" value="0.1" spread="0.02"/>
                    <measurement group_id="O4" value="0.1" spread="0.02"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Absolute Change from Baseline at Month 12</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="95"/>
                    <count group_id="O2" value="92"/>
                    <count group_id="O3" value="97"/>
                    <count group_id="O4" value="95"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.1" spread="0.01"/>
                    <measurement group_id="O2" value="0.1" spread="0.01"/>
                    <measurement group_id="O3" value="0.1" spread="0.01"/>
                    <measurement group_id="O4" value="0.1" spread="0.01"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Patient-Reported Outcomes Measurement Information System (PROMIS-29) Score</title>
        <description>The PROMIS-29 assesses seven health domains: physical function, anxiety, depression, fatigue, sleep disturbance, pain interference, and ability to participate in social roles and activities. Each of the seven domains has four questions which are scored on a five-point Likert scale. The PROMIS-29 scales are scored using a T-score metric method available at the Assessment Center website (http://assessmentcenter.net). A score of 50 points represents the population average for each scale, and 10 points represent one standard deviation. Scores higher than 50 indicate more of the specific scale's construct, which may indicate a desirable or an undesirable outcome.</description>
        <time_frame>Baseline, 1 month, 3 months, 6 months, 9 months, 12 months</time_frame>
        <population>This analysis includes participants who successfully completed this assessment at the indicated post-baseline study visit. Some participants withdrew from the study prior to study completion and some attended study visits but did not complete each study assessment correctly. Participants with incomplete responses are not included in the analysis for that domain.</population>
        <group_list>
          <group group_id="O1">
            <title>Bone Marrow Derived MSCs</title>
            <description>Participants randomized to this arm underwent bone marrow aspiration and then were further randomized to receive a standard orthobiologic injection into the knee joint of autologous bone marrow concentrate (BMAC).</description>
          </group>
          <group group_id="O2">
            <title>Adipose-derived MSCs</title>
            <description>Participants randomized to this arm underwent small volume lipoplasty, and then were further randomized to receive an injection into the knee joint of adipose-derived stromal vascular fraction (SVF).</description>
          </group>
          <group group_id="O3">
            <title>Umbilical Cord Tissue (UCT) MSCs</title>
            <description>Participants randomized to this arm received an injection into the knee joint of cryopreserved doses of umbilical cord tissue MSCs.</description>
          </group>
          <group group_id="O4">
            <title>Corticosteroid Injection</title>
            <description>Participants randomized to the bone marrow derived MSC, adipose-derived MSC, or umbilical cord tissue MSC study arms who were further randomized to the control group and received a corticosteroid (CS) injection into the knee joint.</description>
          </group>
        </group_list>
        <measure>
          <title>Patient-Reported Outcomes Measurement Information System (PROMIS-29) Score</title>
          <description>The PROMIS-29 assesses seven health domains: physical function, anxiety, depression, fatigue, sleep disturbance, pain interference, and ability to participate in social roles and activities. Each of the seven domains has four questions which are scored on a five-point Likert scale. The PROMIS-29 scales are scored using a T-score metric method available at the Assessment Center website (http://assessmentcenter.net). A score of 50 points represents the population average for each scale, and 10 points represent one standard deviation. Scores higher than 50 indicate more of the specific scale's construct, which may indicate a desirable or an undesirable outcome.</description>
          <population>This analysis includes participants who successfully completed this assessment at the indicated post-baseline study visit. Some participants withdrew from the study prior to study completion and some attended study visits but did not complete each study assessment correctly. Participants with incomplete responses are not included in the analysis for that domain.</population>
          <units>t-score</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="114"/>
                <count group_id="O2" value="115"/>
                <count group_id="O3" value="116"/>
                <count group_id="O4" value="116"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Anxiety Score - Baseline</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="114"/>
                    <count group_id="O2" value="115"/>
                    <count group_id="O3" value="116"/>
                    <count group_id="O4" value="116"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="47.1" spread="7.89"/>
                    <measurement group_id="O2" value="47.5" spread="7.79"/>
                    <measurement group_id="O3" value="47.1" spread="7.31"/>
                    <measurement group_id="O4" value="48.2" spread="8.69"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Anxiety Score - Month 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="99"/>
                    <count group_id="O2" value="99"/>
                    <count group_id="O3" value="111"/>
                    <count group_id="O4" value="100"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="45.9" spread="7.46"/>
                    <measurement group_id="O2" value="45.4" spread="7.64"/>
                    <measurement group_id="O3" value="45.9" spread="7.73"/>
                    <measurement group_id="O4" value="45.4" spread="7.83"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Anxiety Score - Month 3</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="98"/>
                    <count group_id="O2" value="100"/>
                    <count group_id="O3" value="104"/>
                    <count group_id="O4" value="100"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="45.1" spread="7.34"/>
                    <measurement group_id="O2" value="45.4" spread="7.91"/>
                    <measurement group_id="O3" value="45.4" spread="7.15"/>
                    <measurement group_id="O4" value="45.5" spread="7.67"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Anxiety Score - Month 6</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="93"/>
                    <count group_id="O2" value="92"/>
                    <count group_id="O3" value="98"/>
                    <count group_id="O4" value="96"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="45.9" spread="7.45"/>
                    <measurement group_id="O2" value="45.8" spread="8.23"/>
                    <measurement group_id="O3" value="45.2" spread="7.51"/>
                    <measurement group_id="O4" value="45.3" spread="6.66"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Anxiety Score - Month 9</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="81"/>
                    <count group_id="O2" value="80"/>
                    <count group_id="O3" value="83"/>
                    <count group_id="O4" value="81"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="46.1" spread="8.04"/>
                    <measurement group_id="O2" value="45.4" spread="7.94"/>
                    <measurement group_id="O3" value="44.9" spread="6.53"/>
                    <measurement group_id="O4" value="45.1" spread="6.88"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Anxiety Score - Month 12</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="94"/>
                    <count group_id="O2" value="91"/>
                    <count group_id="O3" value="98"/>
                    <count group_id="O4" value="96"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="45.6" spread="8.10"/>
                    <measurement group_id="O2" value="45.3" spread="7.46"/>
                    <measurement group_id="O3" value="44.9" spread="7.25"/>
                    <measurement group_id="O4" value="45.2" spread="8.09"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Depression Score - Baseline</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="114"/>
                    <count group_id="O2" value="115"/>
                    <count group_id="O3" value="116"/>
                    <count group_id="O4" value="116"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="44.7" spread="5.70"/>
                    <measurement group_id="O2" value="45.0" spread="6.56"/>
                    <measurement group_id="O3" value="44.9" spread="6.34"/>
                    <measurement group_id="O4" value="45.6" spread="7.61"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Depression Score - Month 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="99"/>
                    <count group_id="O2" value="99"/>
                    <count group_id="O3" value="111"/>
                    <count group_id="O4" value="101"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="44.3" spread="6.54"/>
                    <measurement group_id="O2" value="43.8" spread="6.19"/>
                    <measurement group_id="O3" value="44.9" spread="5.97"/>
                    <measurement group_id="O4" value="45.0" spread="6.92"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Depression Score - Month 3</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="98"/>
                    <count group_id="O2" value="100"/>
                    <count group_id="O3" value="105"/>
                    <count group_id="O4" value="100"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="43.8" spread="5.56"/>
                    <measurement group_id="O2" value="44.0" spread="6.46"/>
                    <measurement group_id="O3" value="44.4" spread="5.88"/>
                    <measurement group_id="O4" value="446" spread="6.60"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Depression Score - Month 6</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="93"/>
                    <count group_id="O2" value="92"/>
                    <count group_id="O3" value="98"/>
                    <count group_id="O4" value="96"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="43.9" spread="5.98"/>
                    <measurement group_id="O2" value="44.9" spread="6.50"/>
                    <measurement group_id="O3" value="44.0" spread="5.44"/>
                    <measurement group_id="O4" value="44.0" spread="5.38"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Depression Score - Month 9</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="81"/>
                    <count group_id="O2" value="80"/>
                    <count group_id="O3" value="83"/>
                    <count group_id="O4" value="80"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="45.6" spread="6.99"/>
                    <measurement group_id="O2" value="45.2" spread="6.71"/>
                    <measurement group_id="O3" value="43.4" spread="5.03"/>
                    <measurement group_id="O4" value="44.1" spread="5.78"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Depression Score - Month 12</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="94"/>
                    <count group_id="O2" value="91"/>
                    <count group_id="O3" value="98"/>
                    <count group_id="O4" value="96"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="44.5" spread="6.33"/>
                    <measurement group_id="O2" value="43.9" spread="6.01"/>
                    <measurement group_id="O3" value="44.3" spread="6.05"/>
                    <measurement group_id="O4" value="44.5" spread="6.65"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Fatigue Score - Baseline</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="114"/>
                    <count group_id="O2" value="114"/>
                    <count group_id="O3" value="116"/>
                    <count group_id="O4" value="116"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="46.8" spread="8.35"/>
                    <measurement group_id="O2" value="47.0" spread="8.29"/>
                    <measurement group_id="O3" value="47.7" spread="7.39"/>
                    <measurement group_id="O4" value="48.5" spread="8.92"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Fatigue Score - Month 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="99"/>
                    <count group_id="O2" value="99"/>
                    <count group_id="O3" value="111"/>
                    <count group_id="O4" value="101"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="45.8" spread="8.94"/>
                    <measurement group_id="O2" value="45.8" spread="8.96"/>
                    <measurement group_id="O3" value="46.9" spread="8.45"/>
                    <measurement group_id="O4" value="46.2" spread="8.55"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Fatigue Score - Month 3</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="98"/>
                    <count group_id="O2" value="99"/>
                    <count group_id="O3" value="105"/>
                    <count group_id="O4" value="100"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="45.0" spread="9.35"/>
                    <measurement group_id="O2" value="45.3" spread="8.50"/>
                    <measurement group_id="O3" value="46.0" spread="7.86"/>
                    <measurement group_id="O4" value="44.8" spread="8.50"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Fatigue Score - Month 6</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="92"/>
                    <count group_id="O2" value="91"/>
                    <count group_id="O3" value="98"/>
                    <count group_id="O4" value="96"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="45.9" spread="9.52"/>
                    <measurement group_id="O2" value="46.1" spread="8.77"/>
                    <measurement group_id="O3" value="44.9" spread="8.57"/>
                    <measurement group_id="O4" value="45.1" spread="8.30"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Fatigue Score - Month 9</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="81"/>
                    <count group_id="O2" value="80"/>
                    <count group_id="O3" value="83"/>
                    <count group_id="O4" value="80"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="46.7" spread="9.39"/>
                    <measurement group_id="O2" value="46.1" spread="8.98"/>
                    <measurement group_id="O3" value="47.1" spread="8.35"/>
                    <measurement group_id="O4" value="46.8" spread="9.70"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Fatigue Score - Month 12</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="94"/>
                    <count group_id="O2" value="90"/>
                    <count group_id="O3" value="98"/>
                    <count group_id="O4" value="96"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="45.6" spread="9.09"/>
                    <measurement group_id="O2" value="45.2" spread="8.26"/>
                    <measurement group_id="O3" value="45.9" spread="8.66"/>
                    <measurement group_id="O4" value="45.3" spread="9.84"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Pain Score - Baseline</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="114"/>
                    <count group_id="O2" value="115"/>
                    <count group_id="O3" value="116"/>
                    <count group_id="O4" value="116"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="59.1" spread="6.06"/>
                    <measurement group_id="O2" value="58.6" spread="6.72"/>
                    <measurement group_id="O3" value="58.9" spread="5.58"/>
                    <measurement group_id="O4" value="60.4" spread="6.56"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Pain Score - Month 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="97"/>
                    <count group_id="O2" value="99"/>
                    <count group_id="O3" value="111"/>
                    <count group_id="O4" value="100"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="53.6" spread="7.76"/>
                    <measurement group_id="O2" value="52.5" spread="6.82"/>
                    <measurement group_id="O3" value="54.8" spread="7.98"/>
                    <measurement group_id="O4" value="53.3" spread="7.81"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Pain Score - Month 3</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="98"/>
                    <count group_id="O2" value="100"/>
                    <count group_id="O3" value="105"/>
                    <count group_id="O4" value="100"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="51.6" spread="8.17"/>
                    <measurement group_id="O2" value="52.1" spread="7.42"/>
                    <measurement group_id="O3" value="52.5" spread="7.86"/>
                    <measurement group_id="O4" value="53.5" spread="8.72"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Pain Score - Month 6</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="92"/>
                    <count group_id="O2" value="92"/>
                    <count group_id="O3" value="98"/>
                    <count group_id="O4" value="97"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="51.5" spread="8.80"/>
                    <measurement group_id="O2" value="51.5" spread="8.00"/>
                    <measurement group_id="O3" value="51.9" spread="7.71"/>
                    <measurement group_id="O4" value="53.6" spread="7.67"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Pain Score - Month 9</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="81"/>
                    <count group_id="O2" value="80"/>
                    <count group_id="O3" value="82"/>
                    <count group_id="O4" value="80"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="52.4" spread="8.55"/>
                    <measurement group_id="O2" value="52.3" spread="8.21"/>
                    <measurement group_id="O3" value="51.8" spread="8.14"/>
                    <measurement group_id="O4" value="53.2" spread="8.77"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Pain Score - Month 12</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="94"/>
                    <count group_id="O2" value="91"/>
                    <count group_id="O3" value="98"/>
                    <count group_id="O4" value="96"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="51.5" spread="8.47"/>
                    <measurement group_id="O2" value="50.8" spread="8.23"/>
                    <measurement group_id="O3" value="51.2" spread="8.26"/>
                    <measurement group_id="O4" value="52.7" spread="8.48"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Physical Function Score - Baseline</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="113"/>
                    <count group_id="O2" value="115"/>
                    <count group_id="O3" value="116"/>
                    <count group_id="O4" value="116"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="39.3" spread="5.30"/>
                    <measurement group_id="O2" value="40.3" spread="5.80"/>
                    <measurement group_id="O3" value="38.8" spread="4.04"/>
                    <measurement group_id="O4" value="38.3" spread="5.10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Physical Function Score - Month 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="97"/>
                    <count group_id="O2" value="98"/>
                    <count group_id="O3" value="111"/>
                    <count group_id="O4" value="100"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="43.0" spread="7.30"/>
                    <measurement group_id="O2" value="43.6" spread="5.48"/>
                    <measurement group_id="O3" value="41.9" spread="6.07"/>
                    <measurement group_id="O4" value="43.3" spread="6.12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Physical Function Score - Month 3</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="97"/>
                    <count group_id="O2" value="98"/>
                    <count group_id="O3" value="105"/>
                    <count group_id="O4" value="101"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="44.9" spread="7.77"/>
                    <measurement group_id="O2" value="44.3" spread="5.84"/>
                    <measurement group_id="O3" value="43.8" spread="6.81"/>
                    <measurement group_id="O4" value="42.9" spread="7.03"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Physical Function Score - Month 6</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="92"/>
                    <count group_id="O2" value="91"/>
                    <count group_id="O3" value="98"/>
                    <count group_id="O4" value="96"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="44.5" spread="7.33"/>
                    <measurement group_id="O2" value="45.2" spread="6.72"/>
                    <measurement group_id="O3" value="44.2" spread="6.59"/>
                    <measurement group_id="O4" value="43.0" spread="6.15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Physical Function Score - Month 9</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="80"/>
                    <count group_id="O2" value="80"/>
                    <count group_id="O3" value="83"/>
                    <count group_id="O4" value="81"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="43.0" spread="7.32"/>
                    <measurement group_id="O2" value="44.6" spread="6.60"/>
                    <measurement group_id="O3" value="44.4" spread="7.17"/>
                    <measurement group_id="O4" value="43.0" spread="6.76"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Physical Function Score - Month 12</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="93"/>
                    <count group_id="O2" value="90"/>
                    <count group_id="O3" value="98"/>
                    <count group_id="O4" value="96"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="44.4" spread="7.81"/>
                    <measurement group_id="O2" value="45.2" spread="7.20"/>
                    <measurement group_id="O3" value="44.8" spread="7.25"/>
                    <measurement group_id="O4" value="43.6" spread="6.84"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Sleep Disturbance Score - Baseline</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="113"/>
                    <count group_id="O2" value="114"/>
                    <count group_id="O3" value="116"/>
                    <count group_id="O4" value="116"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="48.9" spread="7.00"/>
                    <measurement group_id="O2" value="49.7" spread="7.74"/>
                    <measurement group_id="O3" value="50.1" spread="7.92"/>
                    <measurement group_id="O4" value="50.2" spread="8.07"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Sleep Disturbance Score - Month 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="99"/>
                    <count group_id="O2" value="99"/>
                    <count group_id="O3" value="111"/>
                    <count group_id="O4" value="101"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="47.2" spread="7.48"/>
                    <measurement group_id="O2" value="48.4" spread="7.63"/>
                    <measurement group_id="O3" value="48.3" spread="8.66"/>
                    <measurement group_id="O4" value="49.2" spread="7.91"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Sleep Disturbance Score - Month 3</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="97"/>
                    <count group_id="O2" value="99"/>
                    <count group_id="O3" value="104"/>
                    <count group_id="O4" value="101"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="47.3" spread="7.94"/>
                    <measurement group_id="O2" value="48.3" spread="7.85"/>
                    <measurement group_id="O3" value="47.8" spread="7.90"/>
                    <measurement group_id="O4" value="47.9" spread="8.18"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Sleep Disturbance Score - Month 6</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="91"/>
                    <count group_id="O2" value="92"/>
                    <count group_id="O3" value="98"/>
                    <count group_id="O4" value="97"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="48.6" spread="8.31"/>
                    <measurement group_id="O2" value="48.9" spread="6.88"/>
                    <measurement group_id="O3" value="48.1" spread="7.89"/>
                    <measurement group_id="O4" value="48.9" spread="7.38"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Sleep Disturbance Score - Month 9</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="80"/>
                    <count group_id="O2" value="80"/>
                    <count group_id="O3" value="83"/>
                    <count group_id="O4" value="80"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="48.9" spread="7.50"/>
                    <measurement group_id="O2" value="48.5" spread="7.35"/>
                    <measurement group_id="O3" value="48.9" spread="7.77"/>
                    <measurement group_id="O4" value="47.9" spread="8.17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Sleep Disturbance Score - Month 12</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="93"/>
                    <count group_id="O2" value="90"/>
                    <count group_id="O3" value="98"/>
                    <count group_id="O4" value="96"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="47.8" spread="8.42"/>
                    <measurement group_id="O2" value="49.0" spread="7.02"/>
                    <measurement group_id="O3" value="48.7" spread="8.05"/>
                    <measurement group_id="O4" value="48.8" spread="8.08"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Social Roles and Activities Score - Baseline</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="114"/>
                    <count group_id="O2" value="115"/>
                    <count group_id="O3" value="116"/>
                    <count group_id="O4" value="116"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="49.5" spread="8.24"/>
                    <measurement group_id="O2" value="47.9" spread="8.33"/>
                    <measurement group_id="O3" value="48.2" spread="7.18"/>
                    <measurement group_id="O4" value="46.9" spread="7.53"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Social Roles and Activities Score - Month 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="97"/>
                    <count group_id="O2" value="99"/>
                    <count group_id="O3" value="109"/>
                    <count group_id="O4" value="100"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="52.1" spread="8.69"/>
                    <measurement group_id="O2" value="51.6" spread="7.83"/>
                    <measurement group_id="O3" value="51.0" spread="7.65"/>
                    <measurement group_id="O4" value="51.5" spread="8.30"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Social Roles and Activities Score - Month 3</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="98"/>
                    <count group_id="O2" value="100"/>
                    <count group_id="O3" value="105"/>
                    <count group_id="O4" value="101"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="54.4" spread="9.36"/>
                    <measurement group_id="O2" value="53.3" spread="8.18"/>
                    <measurement group_id="O3" value="52.4" spread="8.25"/>
                    <measurement group_id="O4" value="51.6" spread="9.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Social Roles and Activities Score - Month 6</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="92"/>
                    <count group_id="O2" value="92"/>
                    <count group_id="O3" value="98"/>
                    <count group_id="O4" value="97"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="53.1" spread="8.77"/>
                    <measurement group_id="O2" value="52.7" spread="8.32"/>
                    <measurement group_id="O3" value="52.3" spread="8.15"/>
                    <measurement group_id="O4" value="52.0" spread="8.56"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Social Roles and Activities Score - Month 9</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="81"/>
                    <count group_id="O2" value="80"/>
                    <count group_id="O3" value="82"/>
                    <count group_id="O4" value="80"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="53.6" spread="9.02"/>
                    <measurement group_id="O2" value="52.6" spread="8.41"/>
                    <measurement group_id="O3" value="52.8" spread="8.33"/>
                    <measurement group_id="O4" value="52.4" spread="8.47"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Social Roles and Activities Score - Month 12</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="94"/>
                    <count group_id="O2" value="91"/>
                    <count group_id="O3" value="98"/>
                    <count group_id="O4" value="96"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="53.3" spread="9.02"/>
                    <measurement group_id="O2" value="53.5" spread="8.51"/>
                    <measurement group_id="O3" value="53.6" spread="8.05"/>
                    <measurement group_id="O4" value="52.2" spread="8.30"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Overall MRI Grade of Osteoarthritis</title>
        <description>An MRI grade of osteoarthritis was calculated by rating features viewed by MRI (such as cartilage loss) in terms of severity and extent. Total scores range from 0 to 69 with higher values indicating more severe osteoarthritis.</description>
        <time_frame>Baseline, Month 6, Month 12</time_frame>
        <population>This analysis includes participants who successfully completed the MRI assessment at the indicated study visit. Some participants withdrew from the study prior to reaching study visits where the MRI was conducted. Some participants who attended the MRI visit were not able to hold still during the entire MRI and an accurate measurement could not be obtained.</population>
        <group_list>
          <group group_id="O1">
            <title>Bone Marrow Derived MSCs</title>
            <description>Participants randomized to this arm underwent bone marrow aspiration and then were further randomized to receive a standard orthobiologic injection into the knee joint of autologous bone marrow concentrate (BMAC).</description>
          </group>
          <group group_id="O2">
            <title>Adipose-derived MSCs</title>
            <description>Participants randomized to this arm underwent small volume lipoplasty, and then were further randomized to receive an injection into the knee joint of adipose-derived stromal vascular fraction (SVF).</description>
          </group>
          <group group_id="O3">
            <title>Umbilical Cord Tissue (UCT) MSCs</title>
            <description>Participants randomized to this arm received an injection into the knee joint of cryopreserved doses of umbilical cord tissue MSCs.</description>
          </group>
          <group group_id="O4">
            <title>Corticosteroid Injection</title>
            <description>Participants randomized to the bone marrow derived MSC, adipose-derived MSC, or umbilical cord tissue MSC study arms who were further randomized to the control group and received a corticosteroid (CS) injection into the knee joint.</description>
          </group>
        </group_list>
        <measure>
          <title>Overall MRI Grade of Osteoarthritis</title>
          <description>An MRI grade of osteoarthritis was calculated by rating features viewed by MRI (such as cartilage loss) in terms of severity and extent. Total scores range from 0 to 69 with higher values indicating more severe osteoarthritis.</description>
          <population>This analysis includes participants who successfully completed the MRI assessment at the indicated study visit. Some participants withdrew from the study prior to reaching study visits where the MRI was conducted. Some participants who attended the MRI visit were not able to hold still during the entire MRI and an accurate measurement could not be obtained.</population>
          <units>score 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="103"/>
                <count group_id="O2" value="107"/>
                <count group_id="O3" value="108"/>
                <count group_id="O4" value="101"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="103"/>
                    <count group_id="O2" value="107"/>
                    <count group_id="O3" value="108"/>
                    <count group_id="O4" value="101"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="40.5" spread="6.19"/>
                    <measurement group_id="O2" value="39.7" spread="7.82"/>
                    <measurement group_id="O3" value="38.2" spread="7.77"/>
                    <measurement group_id="O4" value="38.9" spread="7.70"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Month 6</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="95"/>
                    <count group_id="O2" value="93"/>
                    <count group_id="O3" value="99"/>
                    <count group_id="O4" value="98"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="40.4" spread="6.27"/>
                    <measurement group_id="O2" value="39.3" spread="7.55"/>
                    <measurement group_id="O3" value="38.3" spread="7.86"/>
                    <measurement group_id="O4" value="39.3" spread="7.88"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Month 12</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="93"/>
                    <count group_id="O2" value="85"/>
                    <count group_id="O3" value="96"/>
                    <count group_id="O4" value="95"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="40.8" spread="6.01"/>
                    <measurement group_id="O2" value="39.8" spread="7.76"/>
                    <measurement group_id="O3" value="37.6" spread="7.81"/>
                    <measurement group_id="O4" value="39.0" spread="7.84"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Information on adverse events was collected from the time participants began receiving the study intervention until the Month 12 follow-up visit.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Bone Marrow Derived MSCs</title>
          <description>Participants randomized to this arm underwent bone marrow aspiration and then were further randomized to receive a standard orthobiologic injection into the knee joint of autologous bone marrow concentrate (BMAC).</description>
        </group>
        <group group_id="E2">
          <title>Adipose-derived MSCs</title>
          <description>Participants randomized to this arm underwent small volume lipoplasty, and then were further randomized to receive an injection into the knee joint of adipose-derived stromal vascular fraction (SVF).</description>
        </group>
        <group group_id="E3">
          <title>Umbilical Cord Tissue (UCT) MSCs</title>
          <description>Participants randomized to this arm received an injection into the knee joint of cryopreserved doses of umbilical cord tissue MSCs.</description>
        </group>
        <group group_id="E4">
          <title>Corticosteroid Injection</title>
          <description>Participants randomized to the bone marrow derived MSC, adipose-derived MSC, or umbilical cord tissue MSC study arms who were further randomized to the control group and received a corticosteroid (CS) injection into the knee joint.</description>
        </group>
      </group_list>
      <serious_events>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="107"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="109"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="108"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="107"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="109"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="116"/>
                <counts group_id="E4" subjects_affected="5" subjects_at_risk="108"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Acute myocardial infarction</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="107"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="109"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="108"/>
              </event>
              <event>
                <sub_title>Myocardial infarction</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="107"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="109"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="116"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="108"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Congenital, familial and genetic disorders</title>
            <event_list>
              <event>
                <sub_title>Atrial fibrillation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="107"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="109"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="108"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Large intestine perforation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="107"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="109"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="108"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Cholecystitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="107"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="109"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="108"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Appendicitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="107"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="109"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="108"/>
              </event>
              <event>
                <sub_title>Clostridium difficile colitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="107"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="109"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="108"/>
              </event>
              <event>
                <sub_title>Abdominal abscess</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="107"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="109"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="108"/>
              </event>
              <event>
                <sub_title>Sepsis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="107"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="109"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="108"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Traumatic pneumothorax</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="107"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="109"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="108"/>
              </event>
              <event>
                <sub_title>Procedural complication</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="107"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="109"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="108"/>
              </event>
              <event>
                <sub_title>Tendon rupture</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="107"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="109"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="116"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="108"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Metastatic breast cancer</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="107"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="109"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="108"/>
              </event>
              <event>
                <sub_title>Invasive ductal breast carcinoma</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="107"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="109"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="108"/>
              </event>
              <event>
                <sub_title>Renal neoplasm</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="107"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="109"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="116"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="108"/>
              </event>
              <event>
                <sub_title>Angina pectoris</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="107"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="109"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="108"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Ischemic stroke</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="107"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="109"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="108"/>
              </event>
              <event>
                <sub_title>Migraine</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="107"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="109"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="108"/>
              </event>
              <event>
                <sub_title>Partial seizures</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="107"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="109"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="116"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="108"/>
              </event>
              <event>
                <sub_title>Radiculopathy</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="107"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="109"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="108"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Nephrolithiasis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="107"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="109"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="108"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Ovarian cyst</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="107"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="109"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="108"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension urgency</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="107"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="109"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="108"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_assessment>Non-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="53" subjects_at_risk="107"/>
                <counts group_id="E2" subjects_affected="64" subjects_at_risk="109"/>
                <counts group_id="E3" subjects_affected="45" subjects_at_risk="116"/>
                <counts group_id="E4" subjects_affected="48" subjects_at_risk="108"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Post procedural contusion</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="107"/>
                <counts group_id="E2" subjects_affected="41" subjects_at_risk="109"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
                <counts group_id="E4" subjects_affected="21" subjects_at_risk="108"/>
              </event>
              <event>
                <sub_title>Post procedural haematoma</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="107"/>
                <counts group_id="E2" subjects_affected="12" subjects_at_risk="109"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
                <counts group_id="E4" subjects_affected="7" subjects_at_risk="108"/>
              </event>
              <event>
                <sub_title>Procedural pain</sub_title>
                <counts group_id="E1" subjects_affected="28" subjects_at_risk="107"/>
                <counts group_id="E2" subjects_affected="37" subjects_at_risk="109"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="116"/>
                <counts group_id="E4" subjects_affected="26" subjects_at_risk="108"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" subjects_affected="27" subjects_at_risk="107"/>
                <counts group_id="E2" subjects_affected="25" subjects_at_risk="109"/>
                <counts group_id="E3" subjects_affected="30" subjects_at_risk="116"/>
                <counts group_id="E4" subjects_affected="28" subjects_at_risk="108"/>
              </event>
              <event>
                <sub_title>Joint stiffness</sub_title>
                <counts group_id="E1" subjects_affected="13" subjects_at_risk="107"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="109"/>
                <counts group_id="E3" subjects_affected="8" subjects_at_risk="116"/>
                <counts group_id="E4" subjects_affected="8" subjects_at_risk="108"/>
              </event>
              <event>
                <sub_title>Joint swelling</sub_title>
                <counts group_id="E1" subjects_affected="19" subjects_at_risk="107"/>
                <counts group_id="E2" subjects_affected="16" subjects_at_risk="109"/>
                <counts group_id="E3" subjects_affected="28" subjects_at_risk="116"/>
                <counts group_id="E4" subjects_affected="8" subjects_at_risk="108"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Kenneth Mautner, MD</name_or_title>
      <organization>Emory University</organization>
      <phone>404-778-7142</phone>
      <email>kmautne@emory.edu</email>
    </point_of_contact>
  </clinical_results>
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03818737
org study id: IRB00108046
nct id: NCT03818737
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
The study is a multicenter trial conducted to compare the effectiveness of an injection of a
      corticosteroid control to mesenchymal stem cell (MSC) preparations from autologous bone
      marrow concentrate (BMAC), adipose derived stem cells in the form of Stromal Vascular
      Fraction (SVF), and third-party human mesenchymal stem cells manufactured from umbilical cord
      tissue (UCT) for the treatment of unilateral Knee Osteoarthritis (OA). The study will be
      conducted in 4 sites in the United States, and a total of 480 participants will be enrolled
      in this study.
Primary osteoarthritis is a debilitating disease characterized by extensive damage to the
      joints and excruciating pain leading to loss of activity and depression. Despite advances in
      diagnosis and relatively efficient control of nociception, to date, the quest for the
      development of a disease modifying osteoarthritis drug has proven unsuccessful. The potential
      of mesenchymal stem cells (MSCs) to inhibit inflammation while promoting healing makes them
      amenable for the treatment of various ailments ranging from cancer to genetic diseases. In
      orthopedic practice, autologous stem cell injections are performed to alleviate the pain
      associated with osteoarthritis. A serious gap in knowledge remains whether the currently used
      cellular treatments are beneficial in the long term and if one cell therapy outperforms
      another.

      The most popular form of autologous MSC therapy has been through the use of autologous bone
      marrow concentrate (BMAC). The rationale is that when a sample of bone marrow aspirate (BMA)
      is collected and the components that are not beneficial to the joint are filtered out (i.e.
      red blood cells, neutrophils, etc.) the remaining concentrate (MSCs, platelets, interleukins,
      etc) can have a "healing" effect on the environment in which it is injected. However it is
      still unknown as to how effective BMAC is for treating orthopedic conditions compared to
      other MSC procedures and the most important components of the BMAC mixture that could aid
      patients suffering from osteoarthritis.

      Adipose tissue has been found to have a large amount of MSCs versus that in bone marrow.
      These cells are currently being used in a variety of clinical research studies within the
      regenerative medicine field. Through a tissue process which includes washing and
      centrifuging, the cellular components can be extracted as a cell pellet, which is also known
      as stromal vascular fraction (SVF). Adipose derived SVF is obtained via liposuction, or the
      removal of adipose tissue via a suction method.

      Although the use of various stem cell preparations for knee osteoarthritis has become
      increasingly prevalent, well-designed studies with conclusive proof of comparative
      effectiveness and identification of the optimal cell source and "dose" have not been
      performed. This study is the first randomized study comparing three types of cellular
      treatments to corticosteroids. The main objective of the study is to identify a superior
      source of stem cells for the treatment of osteoarthritis and validate its advantages over
      corticosteroid injections as the traditional gold standard treatment.

      Participants will be randomized study arms with different types of MSCs (bone marrow derived
      MSC, adipose derived MSC, and umbilical cord tissue MSC) and then will be further randomized
      to receive an injection of the MSC type they were initially assigned to or corticosteroid.
      Participants randomized to bone marrow derived MSC or adipose derived MSC will undergo a
      procedure (bone marrow aspiration or liposuction). Participants will be blinded to whether
      they receive the MSC or corticosteroid injection.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: The study will include a parallel design using a blocked central randomization scheme of 1:1:1:1. Participants will first be randomized to have MSCs derived from either bone marrow, adipose tissue, or umbilical cord tissue. Then they will be further randomized to receive either an injection of MSCs (from bone marrow, adipose, or umbilical cord tissue, depending on the first randomization) or a corticosteroid injection.
primary purpose: Treatment
masking: Single (Participant)
masking description: Participants will not know if they are receiving the MSC or corticosteroid injection.
measure: Change in Visual Analog Pain Scale (VAS-pain) Score
time frame: Baseline, 1 month, 3 months, 6 months, 9 months, 12 months
description: Pain assessment was performed using the Visual Analog Pain Scale (VAS-pain). The VAS-pain is self-completed by the participant. The respondent is asked to place a line perpendicular to the VAS line at the point that represents their pain intensity. Using a ruler, the score is determined by measuring the distance in millimeters (mm) on the line between the "no pain" anchor and the participant's mark, providing a range of scores from 0-100. The recommended cut points for VAS are: no pain (0-4 mm), mild pain (5-44 mm), moderate pain (45-74 mm), and severe pain (75-100 mm). The change in VAS-pain score is the score from the each follow-up visit subtracted from the baseline score. A negative value means that pain has reduced from what it was at baseline.
measure: Change in Knee Injury and Osteoarthritis Outcome Score (KOOS) - Pain Subscale Score
time frame: Baseline, 1 month, 3 months, 6 months, 9 months, 12 months
description: The KOOS questionnaire assesses the participant's opinion about their osteoarthritis and associated problems. It consists of 5 subscales: pain, symptoms, activities of daily living (ADL) function, sport and recreation function, and knee related quality of life (QoL). The pain subscale has 9 items and response options are given on a 5-point Likert scale where 0 = no problems and 4 = extreme problems. Scores are transformed to a scale ranging from 0 to 100 with 0 indicating extreme symptoms and 100 indicating no symptoms. The change in KOOS-pain subscale score is the score from each follow-up visit subtracted from the baseline score. A negative value means that pain has worsened from what it was at baseline, while a positive value means that pain has improved from baseline.
measure: Change in Knee Injury and Osteoarthritis Outcome Score (KOOS) - Total Score
time frame: Baseline, 1 month, 3 months, 6 months, 9 months, 12 months
description: The KOOS questionnaire assesses the participant's opinion about their osteoarthritis and associated problems. It consists of 5 subscales: pain, symptoms, activities of daily living (ADL) function, sport and recreation function, and knee related quality of life (QoL). The KOOS has 42 items across all subscales and response options are given on a 5-point Likert scale where 0 = no problems and 4 = extreme problems. The sum of subscale scores is transformed to a scale ranging from 0 to 100 with 0 indicating extreme symptoms and 100 indicating no symptoms. A negative value means that pain has worsened from what it was at baseline, while a positive value means that pain has improved from baseline.
measure: Change in EuroQuality of Life (EQ-5D-3L) Index Score
time frame: Baseline, 1 month, 3 months, 6 months, 9 months, 12 months
description: The EQ-5D-3L survey measures the severity of five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. The participants will be asked to answer questions regarding these measures and to indicate their current experience on a scale from 1 to 3 (1 being "no problem" and 3 being "most extreme problem"). A sixth item asks participants to rate their current heath from 0 (worst imaginable) to 100 (best imaginable). The answers to these questions are converted into an index value based on the country respondents live in. Health state index scores typically range from less than 0 to 1, where 0 is a health state equivalent to death and 1 is perfect health. Positive values for the change from baseline score indicate improved health.
measure: Patient-Reported Outcomes Measurement Information System (PROMIS-29) Score
time frame: Baseline, 1 month, 3 months, 6 months, 9 months, 12 months
description: The PROMIS-29 assesses seven health domains: physical function, anxiety, depression, fatigue, sleep disturbance, pain interference, and ability to participate in social roles and activities. Each of the seven domains has four questions which are scored on a five-point Likert scale. The PROMIS-29 scales are scored using a T-score metric method available at the Assessment Center website (http://assessmentcenter.net). A score of 50 points represents the population average for each scale, and 10 points represent one standard deviation. Scores higher than 50 indicate more of the specific scale's construct, which may indicate a desirable or an undesirable outcome.
measure: Overall MRI Grade of Osteoarthritis
time frame: Baseline, Month 6, Month 12
description: An MRI grade of osteoarthritis was calculated by rating features viewed by MRI (such as cartilage loss) in terms of severity and extent. Total scores range from 0 to 69 with higher values indicating more severe osteoarthritis.
arm group label: Bone Marrow Derived MSCs
arm group type: Experimental
description: Participants randomized to this arm will undergo bone marrow aspiration and then will be further randomized to receive a standard orthobiologic injection into the knee joint of autologous bone marrow concentrate (BMAC).
arm group label: Adipose-derived MSCs
arm group type: Experimental
description: Participants randomized to this arm will undergo small volume lipoplasty, and then will be further randomized to receive an injection into the knee joint of adipose-derived stromal vascular fraction (SVF).
arm group label: Umbilical Cord Tissue (UCT) MSCs
arm group type: Experimental
description: Participants randomized to this arm will receive an injection into the knee joint of cryopreserved doses of umbilical cord tissue MSCs.
arm group label: Corticosteroid Injection
arm group type: Active Comparator
description: Participants randomized to the bone marrow derived MSC, adipose-derived MSC, or umbilical cord tissue MSC study arms will be further randomized within the arm in a 3:1 ratio to receive either MSCs derived from the study arm of the initial randomization or a corticosteroid (CS) injection. Participants randomized to the control group will receive an injection of corticosteroid into the knee joint.
intervention type: Biological
intervention name: Bone Marrow Derived MSCs
description: Autologous bone marrow concentrate (BMAC) is a standard orthobiologic injection for knee osteoarthritis. The procedure involves harvesting of bone marrow aspirate (BMA) from the posterior superior iliac spine (PSIS) and then following centrifugation in an FDA approved device (EmCyte GenesisCS Pure BMAC®-60 ml) will be injected back into the knee joint. All injections will be made via ultrasound guidance using a standard approach.
arm group label: Bone Marrow Derived MSCs
intervention type: Biological
intervention name: Adipose-derived MSCs
description: Adipose-derived Stromal Vascular Fraction (SVF) will be obtained from a mini lipoaspirate. The lipoaspirate will then be enzymatically digested to produce a SVF that will be injected into the knee joint. All injections will be made via ultrasound guidance using a standard approach.
arm group label: Adipose-derived MSCs
intervention type: Biological
intervention name: Umbilical Cord Tissue (UCT) MSCs
description: Cryopreserved doses of umbilical cord tissue MSCs will be used. These MSCs were cryopreserved at P2 culture in plasmalyte A + 5% human serum albumin in 5 finger cryobags containing 20 million cells in 4 mL and stored under liquid nitrogen until shipment. Cells will be transported in a dry shipper and thawed at the study sites. The dose of MSCs will be aspirated from the cryobag into a sterile syringe and directly injected into the knee. All injections will be made via ultrasound guidance using a standard approach.
arm group label: Umbilical Cord Tissue (UCT) MSCs
intervention type: Drug
intervention name: Corticosteroid injection
description: The corticosteroid injection is prepared by mixing 1cc of 40mg/dL depomedrol and 6cc of normal saline in a 10cc syringe will be made into the knee joint. All injections will be made via ultrasound guidance using a standard approach.
arm group label: Corticosteroid Injection
other name: Depo-Medrol
other name: Methylprednisolone
criteria: 
gender: All
minimum age: 40 Years
maximum age: 70 Years
healthy volunteers: No
last name: Hicham Drissi, PhD
role: Study Director
affiliation: Emory University
last name: Scott D Boden, MD
role: Principal Investigator
affiliation: Emory University
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Emory University
investigator full name: Scott D Boden
investigator title: Professor
mesh term: Osteoarthritis
mesh term: Methylprednisolone
mesh term: Methylprednisolone Acetate
sharing ipd: No
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 