<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/NCT02967874</url>
  </required_header>
  <id_info>
    <org_study_id>IFCI-10/11/2015</org_study_id>
    <nct_id>NCT02967874</nct_id>
  </id_info>
  <brief_title>Autologous Adipose-Derived Stromal Vascular Fraction Cells for Osteoarthritis Treatment</brief_title>
  <official_title>Safety/Efficacy of Intra-articularly Administrated Autologous Adipose -Derived Stromal Vascular Fraction Cells in Treatment of Knee Osteoarthritis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Russian Academy of Medical Sciences</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Russian Academy of Medical Sciences</source>
  <brief_summary>
    <textblock>
      Adipose-derived stromal vascular fraction cells (SVFs) include regenerative cell populations&#xD;
      (hematopoietic cells, pericytes, endothelial cells and progenitors, stromal/stem cells) and&#xD;
      thus are potentially important as new therapeutic tools for the repair and regeneration of&#xD;
      acute and chronically damaged tissues.&#xD;
&#xD;
      The general objective of this study is to evaluate safety and clinical efficacy of a single&#xD;
      intra-articular injection of freshly isolated auto-SVFs for the treatment of patients with&#xD;
      knee osteoarthritis (OA). This study uses autologous adipose-derived SVFs, as therapeutic&#xD;
      agent and intra-articular administration, as a mode of delivery. Expected clinical effects: a&#xD;
      treatment reduces pain, increases function and reduces stiffness in the knees of&#xD;
      osteoarthritic subjects.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Subcutaneous human adipose tissue is an abundant and accessible cell source for applications&#xD;
      in tissue engineering and regenerative medicine. Methods to extract stromal/stem cells from&#xD;
      the waste products of abdominoplasty, cosmetic surgery, and liposuction are now well&#xD;
      developed. Routinely, the adipose tissue is digested with collagenase or related enzymes to&#xD;
      release a heterogeneous population of SVF cells. The SVF cells can be used directly or can be&#xD;
      cultured in plastic ware to select and expand an adherent population known as adipose-derived&#xD;
      stromal/stem cells.&#xD;
&#xD;
      Osteoarthritis is the most common joint disease that affects at least 20% of the world&#xD;
      population. The disease usually begins at the age of 40 years. Radiographic signs of&#xD;
      osteoarthritis are diagnosed in 50% of people aged 55 years and 80% - over 75 years. OA can&#xD;
      cause severe pain and stiffness in the affected joints, thus reducing joint's functionality.&#xD;
      Therefore a treatment that would reduce pain/stiffness and increase joint function would be&#xD;
      of benefit to many people. Safety and feasibility of SVFs in OA patients have been shown in&#xD;
      few clinical studies.&#xD;
&#xD;
      This trial is a prospective, controlled, non-randomized, non-blinded, interventional study to&#xD;
      determine safety and efficacy of a single injection of freshly isolated autologous SVFs into&#xD;
      the knees of osteoarthritic patients (Grade II-III). In experimental group the participants&#xD;
      (n=16) will undergo a standard liposuction to harvest adipose tissue, then the adipose tissue&#xD;
      will be processed to obtain the SVFs and patients will receive a single intra-articular&#xD;
      injection of auto-SVFs into affected knees under the ultrasound navigation. In parallel&#xD;
      control group the participants (n=11) will receive a single intra-articular injection of&#xD;
      hyaluronic acid (Synocrom Forte 2%) under the ultrasound navigation. The safety of auto-SVFs&#xD;
      injection will be evaluated by assessment of the frequency and nature of adverse events&#xD;
      occurring during or immediately after the procedure, and up to the one year following&#xD;
      treatment. Patients will be monitored during 1, 3, 6 and 12- month's visits.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>March 2016</start_date>
  <completion_date type="Actual">September 2019</completion_date>
  <primary_completion_date type="Actual">June 2019</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>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>The number of patients with adverse events</measure>
    <time_frame>up to 12 months after treatment</time_frame>
    <description>The safety of intra-articular injection of auto-SVFs will be evaluated by assessment of the frequency and nature of adverse events during or immediately after the procedure, and up to the 12-months following treatment</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in pain score on the Visual Analogue Scale (VAS) at all follow-up visits</measure>
    <time_frame>Baseline, 1, 3, 6 and 12 months after treatment</time_frame>
    <description>The severity of joint pain, which is determined by the patient from 0 (no pain) to 10 points (unbearable pain), will be evaluated.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Knee injury and Osteoarthritis Outcome Score (KOOS) at all follow-up visits</measure>
    <time_frame>Baseline, 1, 3, 6 and 12 months after treatment</time_frame>
    <description>KOOS consists of 5 subscales; Pain, other Symptoms, Function in daily living (ADL), Function in sport and recreation (Sport/Rec) and knee related Quality of life (QOL). Standardized answer options are given and each question is assigned a score from 0 to 4. A normalized score (100 indicating no symptoms and 0 indicating extreme symptoms) is calculated for each subscale.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Ultrasonography of the knee joints</measure>
    <time_frame>Baseline, 3, 6 and 12 months after treatment</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">27</enrollment>
  <condition>Osteoarthritis</condition>
  <condition>Joint Disease</condition>
  <condition>Osteoarthritis,Knee</condition>
  <condition>Arthritis, Degenerative</condition>
  <condition>Osteoarthrosis</condition>
  <condition>Osteoarthrosis Deformans</condition>
  <arm_group>
    <arm_group_label>Intra-articular auto-SVFs injection</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The participants will undergo a standard liposuction to harvest adipose tissue. The adipose tissue will then be processed to obtain the SVFs.&#xD;
This group of subjects (n=16) will receive a single injection of auto-SVFs into affected knees (3.0 mL cell suspension/joint).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Intra-articular Hyaluronic Acid</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>This group of subjects (n=11) will receive a single injection of Synocrom Forte 2% into affected knees (1.0 mL/joint).</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Intra-articular auto-SVFs injection</intervention_name>
    <description>Liposuction under local anesthesia followed by single intra-articular injection of auto-SVFs under the ultrasound navigation</description>
    <arm_group_label>Intra-articular auto-SVFs injection</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Hyaluronic Acid</intervention_name>
    <description>Single intra-articular injection of Synocrom Forte 2% under the ultrasound navigation</description>
    <arm_group_label>Intra-articular Hyaluronic Acid</arm_group_label>
    <other_name>Synocrom Forte</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age 40 to 85 Years (Adult, Senior)&#xD;
&#xD;
          -  Grade II or Grade III osteoarthritis of the knee joints using Kellgren-Lawrence&#xD;
             grading scale (K-L Grade) as diagnosed using weight bearing X-ray and physician&#xD;
             review, and/or MRI&#xD;
&#xD;
          -  Patients must have continued pain in the knee despite conservative therapies for at&#xD;
             least 3 months&#xD;
&#xD;
          -  Patients must be able to tolerate all study procedures&#xD;
&#xD;
          -  Patients must be willing to voluntarily give written Informed Consent to participate&#xD;
             in the study before any procedures are performed&#xD;
&#xD;
          -  Patients must be willing to be available for all baseline, treatment and follow-up&#xD;
             examinations required by protocol&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Subjects with a BMI &gt; 35&#xD;
&#xD;
          -  Subjects who have had an injection in either knee in the prior 4 weeks, including&#xD;
             corticosteroids, drugs of hyaluronic acid or platelet rich plasma (PRP).&#xD;
&#xD;
          -  Subjects who have had surgery of either knee within 6 months prior to the screening&#xD;
             visit&#xD;
&#xD;
          -  Subjects those are allergic to drugs for local anesthesia&#xD;
&#xD;
          -  Psychiatric disorders&#xD;
&#xD;
          -  Hepatic or renal dysfunctions&#xD;
&#xD;
          -  Hemodynamic or respiratory instability&#xD;
&#xD;
          -  HIV or uncontrolled bacterial, fungal, or viral infections&#xD;
&#xD;
          -  Autoimmune diseases (rheumatoid arthritis, lupus arthropathy, psoriatic arthritis,&#xD;
             etc)&#xD;
&#xD;
          -  Pregnancy&#xD;
&#xD;
          -  Malignancy&#xD;
&#xD;
          -  Participation in other clinical trials&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>40 Years</minimum_age>
    <maximum_age>85 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Elena R Chernykh, MD, PhD</last_name>
    <role>Study Chair</role>
    <affiliation>Institute of Fundamental and Clinical Immunology</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Alexander A Ostanin, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Institute of Fundamental and Clinical Immunology</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Institute of Fundamental and Clinical Immunology</name>
      <address>
        <city>Novosibirsk</city>
        <zip>630099</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Russian Federation</country>
  </location_countries>
  <reference>
    <citation>Michalek J, Moster R, Lukac L, Proefrock K, Petrasovic M, Rybar J, Capkova M, Chaloupka A, Darinskas A, Michalek J Sr, Kristek J, Travnik J, Jabandziev P, Cibulka M, Holek M, Jurik M, Skopalik J, Kristkova Z, Dudasova Z. WITHDRAWN: Autologous adipose tissue-derived stromal vascular fraction cells application in patients with osteoarthritis. Cell Transplant. 2015 Jan 20. doi: 10.3727/096368915X686760. Online ahead of print.</citation>
    <PMID>25706817</PMID>
  </reference>
  <reference>
    <citation>Garza GR, Palomera T, Dumanian GA, Dos-Anjos S. Use of autologous adipose-derived stromal vascular fraction to treat osteoarthritis of the knee: a feasibility and safety study. J Regen Med. 4(1), 2015 doi:10.4172/2325-9620.1000119</citation>
  </reference>
  <verification_date>September 2019</verification_date>
  <study_first_submitted>November 16, 2016</study_first_submitted>
  <study_first_submitted_qc>November 16, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 18, 2016</study_first_posted>
  <last_update_submitted>September 11, 2019</last_update_submitted>
  <last_update_submitted_qc>September 11, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">September 13, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Russian Academy of Medical Sciences</investigator_affiliation>
    <investigator_full_name>Alexander A Ostanin</investigator_full_name>
    <investigator_title>Head of Clinical Department</investigator_title>
  </responsible_party>
  <keyword>Adipose -Derived Stromal Vascular Fraction Cells</keyword>
  <keyword>Knee Osteoarthritis</keyword>
  <keyword>Intra-articular Administration</keyword>
  <keyword>Liposuction</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Osteoarthritis</mesh_term>
    <mesh_term>Osteoarthritis, Knee</mesh_term>
    <mesh_term>Joint Diseases</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/NCT02967874
org study id: IFCI-10/11/2015
nct id: NCT02967874
lead sponsor: 
Adipose-derived stromal vascular fraction cells (SVFs) include regenerative cell populations
      (hematopoietic cells, pericytes, endothelial cells and progenitors, stromal/stem cells) and
      thus are potentially important as new therapeutic tools for the repair and regeneration of
      acute and chronically damaged tissues.

      The general objective of this study is to evaluate safety and clinical efficacy of a single
      intra-articular injection of freshly isolated auto-SVFs for the treatment of patients with
      knee osteoarthritis (OA). This study uses autologous adipose-derived SVFs, as therapeutic
      agent and intra-articular administration, as a mode of delivery. Expected clinical effects: a
      treatment reduces pain, increases function and reduces stiffness in the knees of
      osteoarthritic subjects.
Subcutaneous human adipose tissue is an abundant and accessible cell source for applications
      in tissue engineering and regenerative medicine. Methods to extract stromal/stem cells from
      the waste products of abdominoplasty, cosmetic surgery, and liposuction are now well
      developed. Routinely, the adipose tissue is digested with collagenase or related enzymes to
      release a heterogeneous population of SVF cells. The SVF cells can be used directly or can be
      cultured in plastic ware to select and expand an adherent population known as adipose-derived
      stromal/stem cells.

      Osteoarthritis is the most common joint disease that affects at least 20% of the world
      population. The disease usually begins at the age of 40 years. Radiographic signs of
      osteoarthritis are diagnosed in 50% of people aged 55 years and 80% - over 75 years. OA can
      cause severe pain and stiffness in the affected joints, thus reducing joint's functionality.
      Therefore a treatment that would reduce pain/stiffness and increase joint function would be
      of benefit to many people. Safety and feasibility of SVFs in OA patients have been shown in
      few clinical studies.

      This trial is a prospective, controlled, non-randomized, non-blinded, interventional study to
      determine safety and efficacy of a single injection of freshly isolated autologous SVFs into
      the knees of osteoarthritic patients (Grade II-III). In experimental group the participants
      (n=16) will undergo a standard liposuction to harvest adipose tissue, then the adipose tissue
      will be processed to obtain the SVFs and patients will receive a single intra-articular
      injection of auto-SVFs into affected knees under the ultrasound navigation. In parallel
      control group the participants (n=11) will receive a single intra-articular injection of
      hyaluronic acid (Synocrom Forte 2%) under the ultrasound navigation. The safety of auto-SVFs
      injection will be evaluated by assessment of the frequency and nature of adverse events
      occurring during or immediately after the procedure, and up to the one year following
      treatment. Patients will be monitored during 1, 3, 6 and 12- month's visits.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: The number of patients with adverse events
time frame: up to 12 months after treatment
description: The safety of intra-articular injection of auto-SVFs will be evaluated by assessment of the frequency and nature of adverse events during or immediately after the procedure, and up to the 12-months following treatment
measure: Change in pain score on the Visual Analogue Scale (VAS) at all follow-up visits
time frame: Baseline, 1, 3, 6 and 12 months after treatment
description: The severity of joint pain, which is determined by the patient from 0 (no pain) to 10 points (unbearable pain), will be evaluated.
measure: Change in Knee injury and Osteoarthritis Outcome Score (KOOS) at all follow-up visits
time frame: Baseline, 1, 3, 6 and 12 months after treatment
description: KOOS consists of 5 subscales; Pain, other Symptoms, Function in daily living (ADL), Function in sport and recreation (Sport/Rec) and knee related Quality of life (QOL). Standardized answer options are given and each question is assigned a score from 0 to 4. A normalized score (100 indicating no symptoms and 0 indicating extreme symptoms) is calculated for each subscale.
measure: Change in Ultrasonography of the knee joints
time frame: Baseline, 3, 6 and 12 months after treatment
arm group label: Intra-articular auto-SVFs injection
arm group type: Experimental
description: The participants will undergo a standard liposuction to harvest adipose tissue. The adipose tissue will then be processed to obtain the SVFs.
This group of subjects (n=16) will receive a single injection of auto-SVFs into affected knees (3.0 mL cell suspension/joint).
arm group label: Intra-articular Hyaluronic Acid
arm group type: Active Comparator
description: This group of subjects (n=11) will receive a single injection of Synocrom Forte 2% into affected knees (1.0 mL/joint).
intervention type: Procedure
intervention name: Intra-articular auto-SVFs injection
description: Liposuction under local anesthesia followed by single intra-articular injection of auto-SVFs under the ultrasound navigation
arm group label: Intra-articular auto-SVFs injection
intervention type: Drug
intervention name: Hyaluronic Acid
description: Single intra-articular injection of Synocrom Forte 2% under the ultrasound navigation
arm group label: Intra-articular Hyaluronic Acid
other name: Synocrom Forte
criteria: 
gender: All
minimum age: 40 Years
maximum age: 85 Years
healthy volunteers: No
last name: Elena R Chernykh, MD, PhD
role: Study Chair
affiliation: Institute of Fundamental and Clinical Immunology
last name: Alexander A Ostanin, MD, PhD
role: Principal Investigator
affiliation: Institute of Fundamental and Clinical Immunology
facility: 
country: Russian Federation
citation: Michalek J, Moster R, Lukac L, Proefrock K, Petrasovic M, Rybar J, Capkova M, Chaloupka A, Darinskas A, Michalek J Sr, Kristek J, Travnik J, Jabandziev P, Cibulka M, Holek M, Jurik M, Skopalik J, Kristkova Z, Dudasova Z. WITHDRAWN: Autologous adipose tissue-derived stromal vascular fraction cells application in patients with osteoarthritis. Cell Transplant. 2015 Jan 20. doi: 10.3727/096368915X686760. Online ahead of print.
PMID: 25706817
citation: Garza GR, Palomera T, Dumanian GA, Dos-Anjos S. Use of autologous adipose-derived stromal vascular fraction to treat osteoarthritis of the knee: a feasibility and safety study. J Regen Med. 4(1), 2015 doi:10.4172/2325-9620.1000119
responsible party type: Principal Investigator
investigator affiliation: Russian Academy of Medical Sciences
investigator full name: Alexander A Ostanin
investigator title: Head of Clinical Department
mesh term: Osteoarthritis
mesh term: Osteoarthritis, Knee
mesh term: Joint Diseases
mesh term: Hyaluronic Acid