<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/NCT02219113</url>
  </required_header>
  <id_info>
    <org_study_id>RU-CCH-03-02-14</org_study_id>
    <nct_id>NCT02219113</nct_id>
  </id_info>
  <brief_title>Effectiveness and Safety of Autologous ADRC for Treatment of Degenerative Damage of Knee Articular Cartilage</brief_title>
  <official_title>Effectiveness and Safety of Intraarticular Administration of Autologous Adipose-Derived Regenerative Cells for Treatment of Degenerative Damage of Knee Articular Cartilage</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Central Clinical Hospital w/Outpatient Health Center of Business Administration for the President of Russian Federation</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>I.M. Sechenov First Moscow State Medical University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Central Clinical Hospital w/Outpatient Health Center of Business Administration for the President of Russian Federation</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Autologous adipose-derived regenerative cells (ADRC) extracted using Celution 800/CRS System&#xD;
      (Cytori Therapeutics Inc) from a portion of the fat harvested from the patient's front&#xD;
      abdominal wall. ADRC will be administered one-time intraarticularly. This is a single arm&#xD;
      study with no control. All patients receive cell therapy.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Patients with verified diagnosis knee joint osteoarthritis (degenerative damage of knee&#xD;
      articular cartilage) will undergo knee arthroscopic debridement. 28 days later patients will&#xD;
      will undergo liposuction from front abdominal wall under local anesthesia. After that&#xD;
      autologous ADRC will be extracted using Celution 800/CRS System (Cytori Therapeutics Inc)&#xD;
      from harvested adipose tissue. Extracted ADRC will be administered one-time intraarticularly.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>July 2014</start_date>
  <completion_date type="Actual">April 2017</completion_date>
  <primary_completion_date type="Actual">December 2016</primary_completion_date>
  <phase>Phase 1/Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of serious adverse events (SAEs) and serious adverse reactions (SARs)</measure>
    <time_frame>4 weeks after treatment</time_frame>
    <description>Types, probability and severity of treatment emergent serious adverse events (SAEs) and serious adverse reactions (SARs)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Quality of life monitoring</measure>
    <time_frame>Follow up to completion (up to 24 weeks after treatment)</time_frame>
    <description>Quality of life estimated by validated questionnaires: the Short Form (36) Health Survey (SF-36), Knee Injury and Osteoarthritis Outcome Score (KOOS)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Knee pain intensity monitoring</measure>
    <time_frame>Follow up to completion (up to 24 weeks after treatment)</time_frame>
    <description>Knee pain intensity assessed by Visual Analogue Scale (no pain=0; maximum pain=100 mm)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in knee joint structures</measure>
    <time_frame>Follow up to completion (up to 24 weeks after treatment)</time_frame>
    <description>Changes in knee joint structure assessed by:&#xD;
X-ray (joint space width, bone contour, presence of osteophytes and sclerosis);&#xD;
MRI (articular cartilage, osteophytes, bone marrow abnormality, meniscal integrity, synovial effusion/tissue, anterior and posterior cruciate ligaments, and medial and lateral collateral ligaments);&#xD;
Ultrasonography (effusion, synovial thickening or hypertrophy, cartilage parameters, vascularity, Baker's cysts, osteophytes, tendon and ligament abnormalities, meniscal changes, bursitis, erosions and panniculitis)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in knee function</measure>
    <time_frame>Follow up to completion (up to 24 weeks after treatment)</time_frame>
    <description>Changes in knee function assessed by validated questionnaire: Knee Society Score (KSS)</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">12</enrollment>
  <condition>Knee Joint Osteoarthritis</condition>
  <arm_group>
    <arm_group_label>ADRC injection</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects will undergo liposuction under local anesthesia. Lipoaspirate will be processed to isolate and concentrate adipose-derived regenerative cells (ADRC). After ADRC isolation autologous cells suspension will be injected intraarticularly into knee joint.</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Arthroscopic surgery</intervention_name>
    <arm_group_label>ADRC injection</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Liposuction</intervention_name>
    <arm_group_label>ADRC injection</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>ADRC isolation</intervention_name>
    <description>ADRC isolation performed using Celution 800/CRS System (Cytori Therapeutics Inc) according to manufacturer's protocol</description>
    <arm_group_label>ADRC injection</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Intraarticular administration of autologous ADRC</intervention_name>
    <arm_group_label>ADRC injection</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Pain in the knee joint during more than a half day assessed by VAS (score more than 40&#xD;
             mm)&#xD;
&#xD;
          -  At least three of the following 6 criteria: 50 years of age or older, stiffness&#xD;
             lasting less than 30 minutes, crepitus, bony tenderness, bony enlargement, no warmth&#xD;
             to the touch&#xD;
&#xD;
          -  Patient is able to walk without assistance&#xD;
&#xD;
          -  Patient is familiar with Participant information sheet&#xD;
&#xD;
          -  Patient signed informed consent form&#xD;
&#xD;
        Non-inclusion Criteria:&#xD;
&#xD;
          -  Medical history of endoprosthetic knee replacement&#xD;
&#xD;
          -  Medical history of lower extremity osteotomy&#xD;
&#xD;
          -  Medical history of knee surgery (including arthroscopy) during preceding 1 year prior&#xD;
             to enrollment&#xD;
&#xD;
          -  Medical history of intraarticular injections during preceding 6 months prior to&#xD;
             enrollment&#xD;
&#xD;
          -  Secondary osteoarthritis of the knee joint: posttraumatic osteoarthritis (developed&#xD;
             after clinically significant injury), intra-articular fractures, clinically&#xD;
             significant varus or valgus deformities of lower limbs, septic arthritis, joint's&#xD;
             inflammatory disorders, gout, advanced chondrocalcinosis, Paget's disease, ochronosis,&#xD;
             acromegaly, hemochromatosis, Wilson's disease, primary synovial osteochondromatosis,&#xD;
             osteonecrosis, hemophilia&#xD;
&#xD;
          -  Patients prescribed for immunosuppressive treatment&#xD;
&#xD;
          -  Medical history of systemic autoimmune and inflammatory diseases&#xD;
&#xD;
          -  Significant weight loss (&gt; 10% of body weight in the previous year) of unknown&#xD;
             etiology&#xD;
&#xD;
          -  Medical history of venous thromboembolism or estimated high risk of venous&#xD;
             thromboembolism&#xD;
&#xD;
          -  Patients prescribed for systemic corticosteroids or other medications treatment with&#xD;
             proven impact on bone or cartilage tissue metabolism&#xD;
&#xD;
          -  Clinically significant abnormalities in results of laboratory tests&#xD;
&#xD;
          -  Any conditions limiting compliance (dementia, neuropsychiatric disease, drug and&#xD;
             alcohol abuse etc.)&#xD;
&#xD;
          -  Participation in other clinical trials (or administration of investigational drugs)&#xD;
             during 3 months prior inclusion&#xD;
&#xD;
          -  Patients with malignant tumors including postoperative period, patients receiving&#xD;
             chemotherapy and/or radiotherapy.&#xD;
&#xD;
          -  Patient's activated partial thromboplastin time exceeds normal levels more than 1,8&#xD;
             times&#xD;
&#xD;
          -  Patients prescribed for anticoagulants treatment or patient received anticoagulants at&#xD;
             least one hour prior lipoaspiration&#xD;
&#xD;
          -  Medical history of heterotopic ossifications&#xD;
&#xD;
          -  Patients prescribed for glycoprotein inhibitors treatment&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patient's refusal from the further participation in trial&#xD;
&#xD;
          -  Patient's refusal from compliance with the requirements of contraception during the&#xD;
             participation in research&#xD;
&#xD;
          -  Chronic kidney disease IV- V stages (creatinine clearance &lt; 30 mL/min estimated by&#xD;
             Cockroft-Gault formula)&#xD;
&#xD;
          -  Confirmed syphilis, HIV, hepatitis B or C infections&#xD;
&#xD;
        Dropout Criteria:&#xD;
&#xD;
          -  Pregnancy&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>85 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Sergey V Ivannikov, Professor</last_name>
    <role>Principal Investigator</role>
    <affiliation>I.M. Sechenov First Moscow State Medical University</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Ilya I Eremin, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Federal State Budgetary Institution &quot;Central Clinical Hospital with Outpatient Health Center&quot; of the Business Administration for the President of the Russian Federation; Center for Biomedical Technologies</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Federal State Budgetary Institution &quot;Central Clinical Hospital with Outpatient Health Center&quot; of the Business Administration for the President of the Russian Federation; Center for Biomedical Technologies</name>
      <address>
        <city>Moscow</city>
        <zip>121359</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Russian Federation</country>
  </location_countries>
  <verification_date>July 2017</verification_date>
  <study_first_submitted>August 15, 2014</study_first_submitted>
  <study_first_submitted_qc>August 15, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 18, 2014</study_first_posted>
  <last_update_submitted>July 19, 2017</last_update_submitted>
  <last_update_submitted_qc>July 19, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">July 21, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Damage of articular cartilage</keyword>
  <keyword>Cartilage degeneration</keyword>
  <keyword>Intraarticular injection</keyword>
  <keyword>ADRC</keyword>
  <keyword>Adipose-derived regenerative cells</keyword>
  <keyword>Adipose tissue</keyword>
  <keyword>Stem cells</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Osteoarthritis</mesh_term>
  </condition_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/NCT02219113
org study id: RU-CCH-03-02-14
nct id: NCT02219113
lead sponsor: 
collaborator: 
has dmc: No
Autologous adipose-derived regenerative cells (ADRC) extracted using Celution 800/CRS System
      (Cytori Therapeutics Inc) from a portion of the fat harvested from the patient's front
      abdominal wall. ADRC will be administered one-time intraarticularly. This is a single arm
      study with no control. All patients receive cell therapy.
Patients with verified diagnosis knee joint osteoarthritis (degenerative damage of knee
      articular cartilage) will undergo knee arthroscopic debridement. 28 days later patients will
      will undergo liposuction from front abdominal wall under local anesthesia. After that
      autologous ADRC will be extracted using Celution 800/CRS System (Cytori Therapeutics Inc)
      from harvested adipose tissue. Extracted ADRC will be administered one-time intraarticularly.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of serious adverse events (SAEs) and serious adverse reactions (SARs)
time frame: 4 weeks after treatment
description: Types, probability and severity of treatment emergent serious adverse events (SAEs) and serious adverse reactions (SARs)
measure: Quality of life monitoring
time frame: Follow up to completion (up to 24 weeks after treatment)
description: Quality of life estimated by validated questionnaires: the Short Form (36) Health Survey (SF-36), Knee Injury and Osteoarthritis Outcome Score (KOOS)
measure: Knee pain intensity monitoring
time frame: Follow up to completion (up to 24 weeks after treatment)
description: Knee pain intensity assessed by Visual Analogue Scale (no pain=0; maximum pain=100 mm)
measure: Changes in knee joint structures
time frame: Follow up to completion (up to 24 weeks after treatment)
description: Changes in knee joint structure assessed by:
X-ray (joint space width, bone contour, presence of osteophytes and sclerosis);
MRI (articular cartilage, osteophytes, bone marrow abnormality, meniscal integrity, synovial effusion/tissue, anterior and posterior cruciate ligaments, and medial and lateral collateral ligaments);
Ultrasonography (effusion, synovial thickening or hypertrophy, cartilage parameters, vascularity, Baker's cysts, osteophytes, tendon and ligament abnormalities, meniscal changes, bursitis, erosions and panniculitis)
measure: Changes in knee function
time frame: Follow up to completion (up to 24 weeks after treatment)
description: Changes in knee function assessed by validated questionnaire: Knee Society Score (KSS)
arm group label: ADRC injection
arm group type: Experimental
description: Subjects will undergo liposuction under local anesthesia. Lipoaspirate will be processed to isolate and concentrate adipose-derived regenerative cells (ADRC). After ADRC isolation autologous cells suspension will be injected intraarticularly into knee joint.
intervention type: Procedure
intervention name: Arthroscopic surgery
arm group label: ADRC injection
intervention type: Procedure
intervention name: Liposuction
arm group label: ADRC injection
intervention type: Device
intervention name: ADRC isolation
description: ADRC isolation performed using Celution 800/CRS System (Cytori Therapeutics Inc) according to manufacturer's protocol
arm group label: ADRC injection
intervention type: Other
intervention name: Intraarticular administration of autologous ADRC
arm group label: ADRC injection
criteria: 
gender: All
minimum age: 20 Years
maximum age: 85 Years
healthy volunteers: No
last name: Sergey V Ivannikov, Professor
role: Principal Investigator
affiliation: I.M. Sechenov First Moscow State Medical University
last name: Ilya I Eremin, MD, PhD
role: Principal Investigator
affiliation: Federal State Budgetary Institution "Central Clinical Hospital with Outpatient Health Center" of the Business Administration for the President of the Russian Federation; Center for Biomedical Technologies
facility: 
country: Russian Federation
responsible party type: Sponsor
mesh term: Osteoarthritis