<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/NCT03242707</url>
  </required_header>
  <id_info>
    <org_study_id>HS-17-00365</org_study_id>
    <nct_id>NCT03242707</nct_id>
  </id_info>
  <brief_title>Intra-articular Adipose Tissue Injections for Osteoarthritis</brief_title>
  <official_title>A Randomized, Controlled Study to Evaluate the Efficacy of Intra-articular, Autologous Adipose Tissue Injections for the Treatment of Mild-to-Moderate Osteoarthritis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Southern California</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Southern California</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      A new generation of &quot;minimally manipulated&quot; regenerative treatments are being offered at&#xD;
      clinics across the country, but there is no strong efficacy data to support their use. The&#xD;
      purpose of this study is to estimate the effect size of the treatment by comparing the&#xD;
      efficacy of autologous fat to the current standard of care treatment, hyaluronic acid (HA).&#xD;
      As a secondary aim, we will test for preliminary evidence of efficacy of autologous fat vs.&#xD;
      HA and determine how these treatments effect the biochemical environment of the knee by&#xD;
      comparing pre-injection and post-injection synovial fluid biomarker profiles.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      In recent years, fat treatments administered for structural reconstruction, repair, or&#xD;
      replacement are being increasingly offered at clinics across the country. These treatments&#xD;
      contain both autologous cells that are often referred to as &quot;stem cells&quot; or &quot;MSCs&quot; and&#xD;
      extra-cellular matrix (ECM). Cell therapies containing ECM are thought to have the following&#xD;
      advantages over treatments prepared using enzymatic digestion: (1) preservation of the&#xD;
      stromal vascular niche, which allows time-release of the regenerative factors; (2) release of&#xD;
      bioactive molecules by exosomes, which have been demonstrated to be significantly greater in&#xD;
      mechanically processed fat than enzymatically processed fat; and (3) maintenance of the&#xD;
      structural and morphologic unit, which is thought to increase cell efficacy by making the&#xD;
      cells more resilient to the harsh conditions in the recipient environment. Case reports&#xD;
      investigating the use of autologous fat treatments show promise, but a number of questions&#xD;
      remain unanswered. Agents injected into the joint tend to be quickly cleared from the body&#xD;
      and ECM itself has the potential to produce inflammatory signals and induce osteoarthritis.&#xD;
&#xD;
      This study will use a Hyaluronic acid (HA) as an active control, which is the standard of&#xD;
      care for pain associated with osteoarthritis. The use of HA as an active control for&#xD;
      autologous cell-based therapies is well established and is the best option given the need to&#xD;
      aspirate fat tissue from patients who will be receiving the study treatment.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">July 1, 2018</start_date>
  <completion_date type="Anticipated">December 1, 2020</completion_date>
  <primary_completion_date type="Anticipated">December 1, 2019</primary_completion_date>
  <phase>N/A</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>Participants will be randomly assigned to receive either a single autologous fat injection or a single hyaluronic acid injection.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
    <masking_description>Patients will know which group they have been assigned to</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>The pain items of then Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC-A)</measure>
    <time_frame>Change from baseline WOMAC score at 6 months</time_frame>
    <description>WOMAC-A is a widely used, proprietary set of standardized questionnaires used by health professionals to evaluate the condition of patients with osteoarthritis of the knee and hip, including pain.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Patient-Reported Outcomes Measurement Information System 29-item (PROMIS®-29)</measure>
    <time_frame>Change from baseline in PROMIS-29 from baseline to 6 months</time_frame>
    <description>A collection of 4-item short forms assessing anxiety, depression, fatigue, pain interference, physical function, sleep disturbance, and ability to participate in social roles and activities as well as a single pain intensity item.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Western Ontario and McMaster Universities Osteoarthritis Index</measure>
    <time_frame>Change from baseline in PROMIS-29 from baseline to 6 months</time_frame>
    <description>WOMAC is a widely used, proprietary set of standardized questionnaires used by health professionals to evaluate the condition of patients with osteoarthritis of the knee and hip, including pain, stiffness, and physical functioning of the joints.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical Anchors</measure>
    <time_frame>Clinical anchors from baseline to 6 months</time_frame>
    <description>Clinical anchors will be used to identify minimal important differences in treatment groups</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Synovial fluid analysis</measure>
    <time_frame>Baseline, 6 weeks and 6 months</time_frame>
    <description>Selected OA biomarker profiles that define different OA phenotypes predict the responses to autologous adipose tissue injections</description>
  </other_outcome>
  <other_outcome>
    <measure>Short-term clinical evaluation - WOMAC</measure>
    <time_frame>Change from baseline at 6 weeks</time_frame>
    <description>WOMAC questionnaire will be administered at the 6-week follow-up</description>
  </other_outcome>
  <other_outcome>
    <measure>Short-term clinical evaluation - PROMIS</measure>
    <time_frame>Change from baseline at 6 weeks</time_frame>
    <description>PROMIS questionnaire will be administered at the 6-week follow-up</description>
  </other_outcome>
  <other_outcome>
    <measure>Force Plate Analysis</measure>
    <time_frame>Assessment and change from baseline to 6 weeks and 6 months</time_frame>
    <description>Balance will be assessed using a proprietary force plate system at baseline, 6 weeks and 6 months.</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">54</enrollment>
  <condition>Osteoarthritis, Knee</condition>
  <arm_group>
    <arm_group_label>Autologous adipose tissue knee injection</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Fat will be removed from the abdomen and processed using the Lipogems device. Approximately 5ml of the microfragmented fat product will be injected into the knee joint.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Hyaluronic Acid knee injection</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Hyaluronic Acid - Synvisc-One®: A high molecular weight sodium hyaluronate (HA). HA is an FDA approved, standard of care treatment.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Autologous adipose tissue injection</intervention_name>
    <description>20ml to 40ml of subcutaneous adipose tissue will be aspirated from the abdomen. Adipose tissue will be processed using the Lipogems device, a closed-loop processing device used in medical procedures involving the harvesting, concentrating and transferring of autologous adipose tissue.&#xD;
The resulting fat product will be delivered locally via ultrasound-guided, intra-articular injection.</description>
    <arm_group_label>Autologous adipose tissue knee injection</arm_group_label>
    <other_name>Lipogems, Microfragmented fat</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Hyaluronic Acid</intervention_name>
    <description>Synvisc-One® is a high molecular weight sodium hyaluronate.</description>
    <arm_group_label>Hyaluronic Acid knee injection</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Age 45 to 75, inclusive&#xD;
&#xD;
          2. Normal axial alignment&#xD;
&#xD;
          3. X-ray, Kellgren-Lawrence OA grade 2 - 3, inclusive&#xD;
&#xD;
          4. WOMAC-pain: Between 9 and 19, inclusive&#xD;
&#xD;
          5. Willingness to participate all scheduled follow-ups&#xD;
&#xD;
          6. Willingness to refrain from taking NSAIDs, level 2 analgesics, and opioids for the&#xD;
             course of the study&#xD;
&#xD;
          7. BMI &lt; 40&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Pregnant or lactating&#xD;
&#xD;
          2. Intra-articular injection within 3 months of treatment&#xD;
&#xD;
          3. Inflammatory arthritis&#xD;
&#xD;
          4. Any disease or active drug use that significantly compromises coagulation&#xD;
&#xD;
          5. Significant damage and/or tears of the ACL or other supporting tissues&#xD;
&#xD;
          6. Prior knee surgery in the last 6 months in the knee that will be injected&#xD;
&#xD;
          7. Active tobacco use&#xD;
&#xD;
          8. Active alcohol or substance abuse within 6 months of study entry&#xD;
&#xD;
          9. Known hypersensitivity (allergy) to hyaluronan (sodium hyaluronate) preparations&#xD;
&#xD;
         10. Knee joint infections, skin diseases or infections in the area of the injection site&#xD;
&#xD;
         11. Diabetes&#xD;
&#xD;
         12. Active inhaler use&#xD;
&#xD;
         13. Any medical condition, which in the opinion of the clinical investigator, would&#xD;
             interfere with the treatment or outcome evaluation&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>45 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>C.Thomas Vangsness, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Keck School of Medicine of USC</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>William Fang</last_name>
    <phone>323-442-6959</phone>
    <email>williahf@usc.edu</email>
  </overall_contact>
  <location>
    <facility>
      <name>Keck Medicine of USC</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90033</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>William Fang</last_name>
      <phone>323-442-6959</phone>
      <email>williahf@usc.edu</email>
    </contact>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>October 2019</verification_date>
  <study_first_submitted>July 28, 2017</study_first_submitted>
  <study_first_submitted_qc>August 6, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 8, 2017</study_first_posted>
  <last_update_submitted>October 2, 2019</last_update_submitted>
  <last_update_submitted_qc>October 2, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">October 3, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Southern California</investigator_affiliation>
    <investigator_full_name>Thomas Vangsness</investigator_full_name>
    <investigator_title>Professor of Orthopaedic Surgery</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Osteoarthritis</mesh_term>
    <mesh_term>Osteoarthritis, Knee</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hyaluronic Acid</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</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/NCT03242707
org study id: HS-17-00365
nct id: NCT03242707
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
is us export: No
A new generation of "minimally manipulated" regenerative treatments are being offered at
      clinics across the country, but there is no strong efficacy data to support their use. The
      purpose of this study is to estimate the effect size of the treatment by comparing the
      efficacy of autologous fat to the current standard of care treatment, hyaluronic acid (HA).
      As a secondary aim, we will test for preliminary evidence of efficacy of autologous fat vs.
      HA and determine how these treatments effect the biochemical environment of the knee by
      comparing pre-injection and post-injection synovial fluid biomarker profiles.
In recent years, fat treatments administered for structural reconstruction, repair, or
      replacement are being increasingly offered at clinics across the country. These treatments
      contain both autologous cells that are often referred to as "stem cells" or "MSCs" and
      extra-cellular matrix (ECM). Cell therapies containing ECM are thought to have the following
      advantages over treatments prepared using enzymatic digestion: (1) preservation of the
      stromal vascular niche, which allows time-release of the regenerative factors; (2) release of
      bioactive molecules by exosomes, which have been demonstrated to be significantly greater in
      mechanically processed fat than enzymatically processed fat; and (3) maintenance of the
      structural and morphologic unit, which is thought to increase cell efficacy by making the
      cells more resilient to the harsh conditions in the recipient environment. Case reports
      investigating the use of autologous fat treatments show promise, but a number of questions
      remain unanswered. Agents injected into the joint tend to be quickly cleared from the body
      and ECM itself has the potential to produce inflammatory signals and induce osteoarthritis.

      This study will use a Hyaluronic acid (HA) as an active control, which is the standard of
      care for pain associated with osteoarthritis. The use of HA as an active control for
      autologous cell-based therapies is well established and is the best option given the need to
      aspirate fat tissue from patients who will be receiving the study treatment.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Participants will be randomly assigned to receive either a single autologous fat injection or a single hyaluronic acid injection.
primary purpose: Treatment
masking: None (Open Label)
masking description: Patients will know which group they have been assigned to
measure: The pain items of then Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC-A)
time frame: Change from baseline WOMAC score at 6 months
description: WOMAC-A is a widely used, proprietary set of standardized questionnaires used by health professionals to evaluate the condition of patients with osteoarthritis of the knee and hip, including pain.
measure: Patient-Reported Outcomes Measurement Information System 29-item (PROMIS®-29)
time frame: Change from baseline in PROMIS-29 from baseline to 6 months
description: A collection of 4-item short forms assessing anxiety, depression, fatigue, pain interference, physical function, sleep disturbance, and ability to participate in social roles and activities as well as a single pain intensity item.
measure: Western Ontario and McMaster Universities Osteoarthritis Index
time frame: Change from baseline in PROMIS-29 from baseline to 6 months
description: WOMAC is a widely used, proprietary set of standardized questionnaires used by health professionals to evaluate the condition of patients with osteoarthritis of the knee and hip, including pain, stiffness, and physical functioning of the joints.
measure: Clinical Anchors
time frame: Clinical anchors from baseline to 6 months
description: Clinical anchors will be used to identify minimal important differences in treatment groups
measure: Synovial fluid analysis
time frame: Baseline, 6 weeks and 6 months
description: Selected OA biomarker profiles that define different OA phenotypes predict the responses to autologous adipose tissue injections
measure: Short-term clinical evaluation - WOMAC
time frame: Change from baseline at 6 weeks
description: WOMAC questionnaire will be administered at the 6-week follow-up
measure: Short-term clinical evaluation - PROMIS
time frame: Change from baseline at 6 weeks
description: PROMIS questionnaire will be administered at the 6-week follow-up
measure: Force Plate Analysis
time frame: Assessment and change from baseline to 6 weeks and 6 months
description: Balance will be assessed using a proprietary force plate system at baseline, 6 weeks and 6 months.
arm group label: Autologous adipose tissue knee injection
arm group type: Experimental
description: Fat will be removed from the abdomen and processed using the Lipogems device. Approximately 5ml of the microfragmented fat product will be injected into the knee joint.
arm group label: Hyaluronic Acid knee injection
arm group type: Active Comparator
description: Hyaluronic Acid - Synvisc-One®: A high molecular weight sodium hyaluronate (HA). HA is an FDA approved, standard of care treatment.
intervention type: Biological
intervention name: Autologous adipose tissue injection
description: 20ml to 40ml of subcutaneous adipose tissue will be aspirated from the abdomen. Adipose tissue will be processed using the Lipogems device, a closed-loop processing device used in medical procedures involving the harvesting, concentrating and transferring of autologous adipose tissue.
The resulting fat product will be delivered locally via ultrasound-guided, intra-articular injection.
arm group label: Autologous adipose tissue knee injection
other name: Lipogems, Microfragmented fat
intervention type: Drug
intervention name: Hyaluronic Acid
description: Synvisc-One® is a high molecular weight sodium hyaluronate.
arm group label: Hyaluronic Acid knee injection
criteria: 
gender: All
minimum age: 45 Years
maximum age: 75 Years
healthy volunteers: No
last name: C.Thomas Vangsness, MD
role: Principal Investigator
affiliation: Keck School of Medicine of USC
last name: William Fang
phone: 323-442-6959
email: williahf@usc.edu
facility: 
status: Recruiting
contact: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: University of Southern California
investigator full name: Thomas Vangsness
investigator title: Professor of Orthopaedic Surgery
mesh term: Osteoarthritis
mesh term: Osteoarthritis, Knee
mesh term: Hyaluronic Acid