<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/NCT04456569</url>
  </required_header>
  <id_info>
    <org_study_id>RAD-2019-27368</org_study_id>
    <nct_id>NCT04456569</nct_id>
  </id_info>
  <brief_title>Geniculate Artery Embolization for Osteoarthritis</brief_title>
  <official_title>Geniculate Artery Embolization for Osteoarthritis: Pilot Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Minnesota</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Minnesota</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>Yes</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The need for exploration of more definitive and cost effective non-arthroplasty treatments of&#xD;
      osteoarthritis (OA) has been demonstrated by the orthopedic and health economic research.&#xD;
&#xD;
      Embolotherapy of neovessels associated with OA joints has been shown to be promising in&#xD;
      patients with knee OA. There is a need for level one evidence drawn from randomized clinical&#xD;
      trials to prove the safety, feasibility and efficacy of knee embolotherapy compared to&#xD;
      standard of care.&#xD;
&#xD;
      This randomized pilot study will assign 10 patients with mild-moderate OA to undergo&#xD;
      geniculate artery embolization plus standard of care (defined in this study as: physical&#xD;
      therapy and oral anti-inflammatory medications, with a maximum of 1 joint injection at the&#xD;
      time of enrollment) and 10 patients to receive only medical standard of care (also having had&#xD;
      a maximum of 1 joint injection prior to enrollment). The goal of this pilot study is to&#xD;
      obtain preliminary estimates of safety and efficacy of embolotherapy to provide sustained&#xD;
      symptom control and modify disease progression in patients with mild to moderate knee OA.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a single center, two-arm, open label, pilot study to assess feasibility and safety&#xD;
      and obtain a preliminary estimate of efficacy of geniculate artery embolization in reducing&#xD;
      pain compared to a control group undergoing conservative presurgical management. The 20&#xD;
      patients will be randomly divided into two groups of 10 in 1:1 allocation. One group will&#xD;
      have embolization of the geniculate artery branches and standard of care while the other will&#xD;
      have only the standard care. Following the completion of the 10 participants in each arm, a&#xD;
      safety and data review will be undertaken (Visit 4 in the GAE group and Visit 2 of the SOC).&#xD;
      The data will be assessed regarding the trends between the groups as they relate to&#xD;
      KOOS/WOMAC pain scale, MRI / Xray evaluation of OA, and presence of inflammatory biomarkers.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">February 1, 2022</start_date>
  <completion_date type="Anticipated">February 2024</completion_date>
  <primary_completion_date type="Anticipated">February 2024</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Safety as Assessed by Grade 3-4 Adverse events</measure>
    <time_frame>12 months</time_frame>
    <description>Safety will be reported using the combined number of grade 3 and 4 adverse events that occur in each arm.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in Knee Injury and Osteoarthritis Outcome Score (KOOS)</measure>
    <time_frame>baseline, 1 month, 6 months, 12 months</time_frame>
    <description>The KOOS measures 5 patient-relevant dimensions, each scored separately:&#xD;
Pain (nine items); Symptoms (seven items); ADL Function (17 items); Sport and Recreation Function (five items); Quality of Life (four items).&#xD;
Items are rated on a 5-point Likert scale from 0 (No problems) to 4 (Extreme problems). Dimension scores are calculated as the mean score of the included items divided by 4 and multiplied by 100. Range of subscale scores is 0-100 with higher scores indicating better function.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC)</measure>
    <time_frame>baseline, 1 month, 6 months, 12 months</time_frame>
    <description>The Western Ontario and McMaster Universities Arthritis Index (WOMAC) is a self-administered questionnaire consisting of 24 items divided into 3 subscales: Pain (5 items), stiffness (2 items), and physical function (17 items). Items are rated on a Likert scale of 0 (extreme) to 4 (none). Raw sub-scale scores are normalized to produce percentage scores in accordance with the KOOS by multiplying each score by 100/96. Total scores are a sum of the normalized sub-scales scores and range 0-100, with higher scores indicating better functioning.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>IL-6 Concentration</measure>
    <time_frame>baseline, 1 month, 12 months</time_frame>
    <description>Interleukin-6 concentrations will be measured in the serum and joint aspirate and reported in units of pg/ml.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Prostaglandin E2 Concentration</measure>
    <time_frame>baseline, 1 month, 12 months</time_frame>
    <description>Prostaglandin E2 concentrations will be measured in the serum and joint aspirate and reported in units of pg/ml.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Matrix Metalloprotinase 1 Concentration</measure>
    <time_frame>baseline, 1 month, 12 months</time_frame>
    <description>Matrix Metalloprotinase 1 concentrations will be measured in the serum and joint aspirate and reported in units of ng/ml.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Vascular Endothelial Growth Factor Concentration</measure>
    <time_frame>baseline, 1 month, 12 months</time_frame>
    <description>Vascular Endothelial Growth Factor concentrations will be measured in the serum and joint aspirate and reported in units of pg/ml.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>C-Reactive Protein Concentration</measure>
    <time_frame>baseline, 1 month, 12 months</time_frame>
    <description>C-Reactive Protein concentrations will be measured in the serum and reported in units of mg/L.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Erythrocyte Sedimentation Rate</measure>
    <time_frame>baseline, 1 month, 12 months</time_frame>
    <description>Erythrocyte sedimentation rate will be performed using serum and reported in units of mm/hr.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Feasibility as Assessed by Protocol Adherence</measure>
    <time_frame>12 months</time_frame>
    <description>Feasibility will be assessed and reported as the number of participants in each arm who drop out due to a lack of protocol adherence.</description>
  </other_outcome>
  <other_outcome>
    <measure>Feasibility as Assessed by Recruitment Rate</measure>
    <time_frame>12 months</time_frame>
    <description>Feasibility will be assessed and reported as the mean number of participants who are enrolled each month over the length of the study (12 months).</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">20</enrollment>
  <condition>Osteo Arthritis Knee</condition>
  <condition>Arthritis</condition>
  <condition>Osteoarthritis</condition>
  <condition>Osteoarthritis, Knee</condition>
  <arm_group>
    <arm_group_label>GAE + Standard of Care</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants in this arm will receive geniculate artery embolization and standard of care.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Standard of Care</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Participants in this arm will receive standard of care only.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Geniculate Artery Embolization</intervention_name>
    <description>All patients within the embolization group will undergo unilateral angiography and embolization of the appropriate treatment limb geniculate arteries. For patients with bilateral disease the more clinically symptomatic side will be chosen as the treatment/control knee.</description>
    <arm_group_label>GAE + Standard of Care</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Unilaterally dominant symptomatic osteoarthritis (bilateral radiographic OA will not&#xD;
             exclude)&#xD;
&#xD;
          -  Patients who are symptomatically refractory of at least 3 months of medical and/or&#xD;
             rehabilitation measures (anti-inflammatory drugs, and/or physical therapy, and/or&#xD;
             strength conditioning, and/or 0-1 intra-articular injections of the affected knee)&#xD;
&#xD;
          -  Kellgren-Lawrence grade 1, 2, or 3 on radiograph of the knee&#xD;
&#xD;
          -  Patients who are willing to comply with the protocol requirements and willing to&#xD;
             undergo non-contrast MRI 1-30 days prior to procedure and at 12 months following&#xD;
             procedure&#xD;
&#xD;
          -  Patients who are willing to comply with regular follow up during the 12 month&#xD;
             follow-up period&#xD;
&#xD;
          -  Patients who have been evaluated by an orthopaedic surgeon or sports medicine provider&#xD;
             and deemed to not be a current candidate for partial or total knee arthroplasty. These&#xD;
             patients do, however, need to be considered a potential candidate for partial or total&#xD;
             knee as an end point following the natural history of osteoarthritis.&#xD;
&#xD;
          -  Patients with WOMAC Score &gt;=6 in at least 2 categories&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients with a weight &gt;250 pounds&#xD;
&#xD;
          -  Patients with advanced peripheral arterial disease (resting ABI &lt;= 0.9)&#xD;
&#xD;
          -  Patients with known significant peripheral arterial disease precluding common femoral&#xD;
             catheterization&#xD;
&#xD;
          -  Patients who do smoke or have smoked tobacco regularly (smoking 1 or more tobacco&#xD;
             product(s) per week) within the last year&#xD;
&#xD;
          -  Patients with diabetes who have a hemoglobin A1C of &gt;9%&#xD;
&#xD;
          -  Patients who have undergone previous lower extremity embolization&#xD;
&#xD;
          -  Patients with uncontrolled emotional disorders per patient medical history&#xD;
&#xD;
          -  Patients with chronic pain syndrome or currently under a pain contract&#xD;
&#xD;
          -  Patients with anatomic variants involving the lower extremities which would increase&#xD;
             the risk of non-target embolization&#xD;
&#xD;
          -  Patients with renal insufficiency based on an estimated GFR&lt;45 ml/min who are not&#xD;
             already on hemodialysis.&#xD;
&#xD;
          -  Patients with an abnormal INR (&gt;1.5).&#xD;
&#xD;
          -  Patients with a platelet count &lt;50x109/L.&#xD;
&#xD;
          -  Patients who are currently receiving medications for anticoagulation which cannot&#xD;
             safely be held for the procedure and for 7 days post-procedure.&#xD;
&#xD;
          -  Patients with a known severe allergy to iodine which cannot be adequately&#xD;
             pre-medicated&#xD;
&#xD;
          -  Patients who are pregnant or intend to become pregnant within 6 months of the&#xD;
             procedure&#xD;
&#xD;
          -  Patients with a contraindication to drugs used for moderate sedation during&#xD;
             interventional procedures, including Midazolam and Fentanyl&#xD;
&#xD;
          -  Patients with a life expectancy &lt;60 months&#xD;
&#xD;
          -  Patients who are currently enrolled or who plan to enroll in other investigations that&#xD;
             conflict with follow-up testing or confounds data in this trial&#xD;
&#xD;
          -  Patients with contraindications to medical and physical rehabilitative treatments of&#xD;
             OA&#xD;
&#xD;
          -  Patients with known advanced atherosclerosis&#xD;
&#xD;
          -  Patients with known current or previous lower extremity fistula&#xD;
&#xD;
          -  Patients with rheumatoid arthritis or seronegative arthropathies&#xD;
&#xD;
          -  Patients with prior ipsilateral knee surgery.&#xD;
&#xD;
          -  Patients with WOMAC Pain Scale &lt; 6&#xD;
&#xD;
          -  Patients having received more than one steroid injection in the affected joint or an&#xD;
             injection in the affected joint within 3 months of screening&#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>Reza Talaie, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Minnesota</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Connie Dale, MD</last_name>
    <email>dalex179@umn.edu</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Allison Wolf, MPH</last_name>
    <email>wolfx494@umn.edu</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>University of Minnesota</name>
      <address>
        <city>Minneapolis</city>
        <state>Minnesota</state>
        <zip>55455</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Reza Talaie, MD</last_name>
    </contact>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>July 2023</verification_date>
  <study_first_submitted>June 29, 2020</study_first_submitted>
  <study_first_submitted_qc>June 29, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 2, 2020</study_first_posted>
  <last_update_submitted>July 10, 2023</last_update_submitted>
  <last_update_submitted_qc>July 10, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">July 12, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Embolotherapy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Arthritis</mesh_term>
    <mesh_term>Osteoarthritis</mesh_term>
    <mesh_term>Osteoarthritis, Knee</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/NCT04456569
org study id: RAD-2019-27368
nct id: NCT04456569
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: Yes
The need for exploration of more definitive and cost effective non-arthroplasty treatments of
      osteoarthritis (OA) has been demonstrated by the orthopedic and health economic research.

      Embolotherapy of neovessels associated with OA joints has been shown to be promising in
      patients with knee OA. There is a need for level one evidence drawn from randomized clinical
      trials to prove the safety, feasibility and efficacy of knee embolotherapy compared to
      standard of care.

      This randomized pilot study will assign 10 patients with mild-moderate OA to undergo
      geniculate artery embolization plus standard of care (defined in this study as: physical
      therapy and oral anti-inflammatory medications, with a maximum of 1 joint injection at the
      time of enrollment) and 10 patients to receive only medical standard of care (also having had
      a maximum of 1 joint injection prior to enrollment). The goal of this pilot study is to
      obtain preliminary estimates of safety and efficacy of embolotherapy to provide sustained
      symptom control and modify disease progression in patients with mild to moderate knee OA.
This is a single center, two-arm, open label, pilot study to assess feasibility and safety
      and obtain a preliminary estimate of efficacy of geniculate artery embolization in reducing
      pain compared to a control group undergoing conservative presurgical management. The 20
      patients will be randomly divided into two groups of 10 in 1:1 allocation. One group will
      have embolization of the geniculate artery branches and standard of care while the other will
      have only the standard care. Following the completion of the 10 participants in each arm, a
      safety and data review will be undertaken (Visit 4 in the GAE group and Visit 2 of the SOC).
      The data will be assessed regarding the trends between the groups as they relate to
      KOOS/WOMAC pain scale, MRI / Xray evaluation of OA, and presence of inflammatory biomarkers.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Outcomes Assessor)
measure: Safety as Assessed by Grade 3-4 Adverse events
time frame: 12 months
description: Safety will be reported using the combined number of grade 3 and 4 adverse events that occur in each arm.
measure: Change in Knee Injury and Osteoarthritis Outcome Score (KOOS)
time frame: baseline, 1 month, 6 months, 12 months
description: The KOOS measures 5 patient-relevant dimensions, each scored separately:
Pain (nine items); Symptoms (seven items); ADL Function (17 items); Sport and Recreation Function (five items); Quality of Life (four items).
Items are rated on a 5-point Likert scale from 0 (No problems) to 4 (Extreme problems). Dimension scores are calculated as the mean score of the included items divided by 4 and multiplied by 100. Range of subscale scores is 0-100 with higher scores indicating better function.
measure: Change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC)
time frame: baseline, 1 month, 6 months, 12 months
description: The Western Ontario and McMaster Universities Arthritis Index (WOMAC) is a self-administered questionnaire consisting of 24 items divided into 3 subscales: Pain (5 items), stiffness (2 items), and physical function (17 items). Items are rated on a Likert scale of 0 (extreme) to 4 (none). Raw sub-scale scores are normalized to produce percentage scores in accordance with the KOOS by multiplying each score by 100/96. Total scores are a sum of the normalized sub-scales scores and range 0-100, with higher scores indicating better functioning.
measure: IL-6 Concentration
time frame: baseline, 1 month, 12 months
description: Interleukin-6 concentrations will be measured in the serum and joint aspirate and reported in units of pg/ml.
measure: Prostaglandin E2 Concentration
time frame: baseline, 1 month, 12 months
description: Prostaglandin E2 concentrations will be measured in the serum and joint aspirate and reported in units of pg/ml.
measure: Matrix Metalloprotinase 1 Concentration
time frame: baseline, 1 month, 12 months
description: Matrix Metalloprotinase 1 concentrations will be measured in the serum and joint aspirate and reported in units of ng/ml.
measure: Vascular Endothelial Growth Factor Concentration
time frame: baseline, 1 month, 12 months
description: Vascular Endothelial Growth Factor concentrations will be measured in the serum and joint aspirate and reported in units of pg/ml.
measure: C-Reactive Protein Concentration
time frame: baseline, 1 month, 12 months
description: C-Reactive Protein concentrations will be measured in the serum and reported in units of mg/L.
measure: Erythrocyte Sedimentation Rate
time frame: baseline, 1 month, 12 months
description: Erythrocyte sedimentation rate will be performed using serum and reported in units of mm/hr.
measure: Feasibility as Assessed by Protocol Adherence
time frame: 12 months
description: Feasibility will be assessed and reported as the number of participants in each arm who drop out due to a lack of protocol adherence.
measure: Feasibility as Assessed by Recruitment Rate
time frame: 12 months
description: Feasibility will be assessed and reported as the mean number of participants who are enrolled each month over the length of the study (12 months).
arm group label: GAE + Standard of Care
arm group type: Experimental
description: Participants in this arm will receive geniculate artery embolization and standard of care.
arm group label: Standard of Care
arm group type: No Intervention
description: Participants in this arm will receive standard of care only.
intervention type: Device
intervention name: Geniculate Artery Embolization
description: All patients within the embolization group will undergo unilateral angiography and embolization of the appropriate treatment limb geniculate arteries. For patients with bilateral disease the more clinically symptomatic side will be chosen as the treatment/control knee.
arm group label: GAE + Standard of Care
criteria: 
gender: All
minimum age: 40 Years
maximum age: 70 Years
healthy volunteers: No
last name: Reza Talaie, MD
role: Principal Investigator
affiliation: University of Minnesota
last name: Connie Dale, MD
email: dalex179@umn.edu
last name: Allison Wolf, MPH
email: wolfx494@umn.edu
facility: 
status: Recruiting
contact: 
country: United States
responsible party type: Sponsor
mesh term: Arthritis
mesh term: Osteoarthritis
mesh term: Osteoarthritis, Knee