<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/NCT04443166</url>
  </required_header>
  <id_info>
    <org_study_id>N202002101</org_study_id>
    <nct_id>NCT04443166</nct_id>
  </id_info>
  <brief_title>The Synergistic Effects of Intra-articular Hyaluronic Acid and Platelet-rich Plasma Injections on Knee Osteoarthritis</brief_title>
  <acronym>HAPRP</acronym>
  <official_title>The Synergistic Effects of Intra-articular Hyaluronic Acid and Platelet-rich Plasma Injections on Knee Osteoarthritis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Taipei Medical University WanFang Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Taipei Medical University WanFang Hospital</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>Yes</is_fda_regulated_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Although intra-articular knee injection with platelet-rich plasma (PRP) may have better&#xD;
      outcomes than using hyaluronic acid (HA) for people with knee osteoarthritis (OA), it is&#xD;
      expensive to use PRP. Programs with a combination of PRP and HA (PRP+HA) showed good results&#xD;
      in vitro and animal studies. This 2-year study aims to clarify the short- and long-term&#xD;
      effectiveness of the PRP+HA program for knee OA.&#xD;
&#xD;
      The study will recruit 60 persons aged between 50 and 80 years who have experienced&#xD;
      symptomatic knee OA for 6 months or more and have a radiographic picture of knee OA of grades&#xD;
      1-3, based on the Kellegren-Lawrence scale. Those who have diabetes, fever, anemia (Hb &lt;10&#xD;
      g/dl), thrombocytopenia (platelet count &lt;150000/ml), a blood-clotting disease, knee deformity&#xD;
      (genu valgum/varum &gt;20 degrees), impaired leg mobility secondary to neuromuscular diseases or&#xD;
      a bony fracture, impaired mental function, severe cardiopulmonary impairment, taking&#xD;
      anticoagulants long-term, a history of intra-articular steroid injection in the prior 1 year,&#xD;
      a history of knee injury involving ligaments and menisci, and a history of malignancy are&#xD;
      excluded.&#xD;
&#xD;
      All participants will be randomly divided into group A and group B. At the beginning of the&#xD;
      study (T0), group A will receive one course of PRP+HA program and group B will receive one HA&#xD;
      course (a single HA injection (Hyajoint) weekly for 3 weeks). The PRP+HA program includes 3&#xD;
      HA injections and a single PRP injection (Arthrex double syringe system). In the 6th month,&#xD;
      alternately, group B will receive one PRP+HA program and group A will receive one HA course.&#xD;
      The study has 3 outcome assessment tools including a self-administered Western Ontario and&#xD;
      McMaster Universities (WOMAC) Osteoarthritis Index, measurement of quadriceps strength with a&#xD;
      digital handheld dynamometer, and measurement of femoral condylar cartilage thickness with&#xD;
      musculoskeletal ultrasound. The investigators will conduct those assessments in the beginning&#xD;
      (T0) of the study and the following 1st (T1), 3rd (T2), 6th (T3), and 9th (T4) months.&#xD;
&#xD;
      In the 18th month following the beginning of the study, both groups will receive a booster&#xD;
      course of PRP+HA program. During the first week of the program, group A will receive a HA&#xD;
      injection before the PRP injection and group B will receive the HA injection after the PRP&#xD;
      injection. The investigators will conduct the long-term assessments in the 12th (T5), 15th&#xD;
      (T6), 18th (T7), and 21st (T8) months since the beginning of the study.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      People aged &gt;65 years are over 14% in Taiwan since the year 2018. Knee osteoarthritis (OA) is&#xD;
      prevalent among elderly people. People with knee OA often have knee pain and stiffness as&#xD;
      well as compromised their walking performance and quality of daily life. Although&#xD;
      intra-articular knee injection with platelet-rich plasma (PRP) may have better outcomes than&#xD;
      using hyaluronic acid (HA), it is expensive to use PRP. Programs with a combination of PRP&#xD;
      and HA (PRP+HA) showed good results in vitro and animal studies. This 2-year study aims to&#xD;
      clarify the short- and long-term effectiveness of the PRP+HA program for knee OA. The study&#xD;
      will also assess the effectiveness of a booster course of PRP+HA program in the second year.&#xD;
&#xD;
      The study will recruit 60 persons aged between 50 and 80 years who have experienced&#xD;
      symptomatic knee OA for 6 months or more and have a radiographic picture of knee OA of grades&#xD;
      1-3, based on the Kellegren-Lawrence scale. Those who have diabetes, fever, anemia (Hb &lt;10&#xD;
      g/dl), thrombocytopenia (platelet count &lt;150000/ml), a blood-clotting disease, knee deformity&#xD;
      (genu valgum/varum &gt;20 degrees), impaired leg mobility secondary to neuromuscular diseases or&#xD;
      a bony fracture, impaired mental function who have difficulty in completing outcome&#xD;
      assessments, severe cardiopulmonary impairment, taking anticoagulants long-term, a history of&#xD;
      intra-articular steroid injection in the prior 1 year, a history of knee injury involving&#xD;
      ligaments and menisci, and a history of malignancy are excluded.&#xD;
&#xD;
      All participants will be randomly divided into group A and group B. At the beginning of the&#xD;
      study (T0), group A will receive one course of PRP+HA program and group B will receive one HA&#xD;
      course (a single HA injection (Hyajoint) weekly for 3 weeks). The PRP+HA program includes 3&#xD;
      HA injections and a single PRP injection (Arthrex double syringe system). In the 6th month,&#xD;
      alternately, group B will receive one PRP+HA program and group A will receive one HA course.&#xD;
      The study has 3 outcome assessment tools including a self-administered Western Ontario and&#xD;
      McMaster Universities (WOMAC) Osteoarthritis Index, measurement of quadriceps strength with a&#xD;
      digital handheld dynamometer, and measurement of femoral condylar cartilage thickness with&#xD;
      musculoskeletal ultrasound. The investigators will conduct those assessments in the beginning&#xD;
      (T0) of the study and the following 1st (T1), 3rd (T2), 6th (T3), and 9th (T4) months.&#xD;
&#xD;
      In the 18th month following the beginning of the study, both groups will receive a booster&#xD;
      course of PRP+HA program. During the first week of the program, group A will receive a HA&#xD;
      injection before the PRP injection and group B will receive the HA injection after the PRP&#xD;
      injection. The investigators will conduct the long-term assessments in the 12th (T5), 15th&#xD;
      (T6), 18th (T7), and 21st (T8) months since the beginning of the study.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date type="Anticipated">June 2020</start_date>
  <completion_date type="Anticipated">June 2022</completion_date>
  <primary_completion_date type="Anticipated">June 2021</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>Crossover Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>changes in WOMAC index</measure>
    <time_frame>in the beginning (T0) of the study and the following 1st (T1), 3rd (T2), 6th (T3), 9th (T4), 12th (T5), 15th (T6), 18th (T7), and 21st (T8) months.</time_frame>
    <description>a self-administered Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index</description>
  </primary_outcome>
  <primary_outcome>
    <measure>changes in quadriceps strength</measure>
    <time_frame>in the beginning (T0) of the study and the following 1st (T1), 6th (T3), 12th (T5), 18th (T7), and 21st (T8) months.</time_frame>
    <description>measurement of quadriceps strength with a digital handheld dynamometer</description>
  </primary_outcome>
  <primary_outcome>
    <measure>changes in cartilage thickness</measure>
    <time_frame>in the beginning (T0) of the study and the following 1st (T1), 6th (T3), 12th (T5), 18th (T7), and 21st (T8) months.</time_frame>
    <description>measurement of femoral condylar cartilage thickness with musculoskeletal ultrasound</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">60</enrollment>
  <condition>Osteoarthritis Knees Both</condition>
  <arm_group>
    <arm_group_label>Group A</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>At the beginning of the study (T0), group A will receive one course of PRP+HA program and group B will receive one HA course (a single HA injection (Hyajoint) weekly for 3 weeks). The PRP+HA program includes 3 HA injections and a single PRP injection (Arthrex double syringe system).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group B</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>In the 6th month, alternately, group B will receive one PRP+HA program and group A will receive one HA course.</description>
  </arm_group>
  <intervention>
    <intervention_type>Combination Product</intervention_type>
    <intervention_name>A platelet-rich plasma (PRP)+ hyaluronic acid (HA) program</intervention_name>
    <description>a combination of intra-articular knee injection with platelet-rich plasma (PRP) and hyaluronic acid (HA)</description>
    <arm_group_label>Group A</arm_group_label>
    <arm_group_label>Group B</arm_group_label>
    <other_name>A hyaluronic acid (HA) course (a single HA injection (Hyajoint) weekly for 3 weeks)</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  The study will recruit persons aged between 50 and 80 years who have experienced&#xD;
             symptomatic knee OA for 6 months or more. They have a radiographic picture of knee OA&#xD;
             of grades 1-3, based on the Kellegren-Lawrence scale.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Those who have diabetes, fever, anemia (Hb &lt;10 g/dl), thrombocytopenia (platelet count&#xD;
             &lt;150000/ml), a blood-clotting disease, knee deformity (genu valgum/varum &gt;20 degrees),&#xD;
             impaired leg mobility secondary to neuromuscular diseases or a bony fracture, impaired&#xD;
             mental function who have difficulty in completing outcome assessments, severe&#xD;
             cardiopulmonary impairment, taking anticoagulants long-term, a history of&#xD;
             intra-articular steroid injection in the prior 1 year, a history of knee injury&#xD;
             involving ligaments and menisci, and a history of malignancy are excluded.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>50 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Kwang-Hwa Chang, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Prof.</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Kwang-Hwa Chang, MD</last_name>
    <phone>+886-2-29307930</phone>
    <phone_ext>1610</phone_ext>
    <email>chang2773@gmail.com</email>
  </overall_contact>
  <verification_date>June 2020</verification_date>
  <study_first_submitted>June 10, 2020</study_first_submitted>
  <study_first_submitted_qc>June 22, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 23, 2020</study_first_posted>
  <last_update_submitted>June 22, 2020</last_update_submitted>
  <last_update_submitted_qc>June 22, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">June 23, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </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>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- 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/NCT04443166
org study id: N202002101
nct id: NCT04443166
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: Yes
is us export: Yes
Although intra-articular knee injection with platelet-rich plasma (PRP) may have better
      outcomes than using hyaluronic acid (HA) for people with knee osteoarthritis (OA), it is
      expensive to use PRP. Programs with a combination of PRP and HA (PRP+HA) showed good results
      in vitro and animal studies. This 2-year study aims to clarify the short- and long-term
      effectiveness of the PRP+HA program for knee OA.

      The study will recruit 60 persons aged between 50 and 80 years who have experienced
      symptomatic knee OA for 6 months or more and have a radiographic picture of knee OA of grades
      1-3, based on the Kellegren-Lawrence scale. Those who have diabetes, fever, anemia (Hb <10
      g/dl), thrombocytopenia (platelet count <150000/ml), a blood-clotting disease, knee deformity
      (genu valgum/varum >20 degrees), impaired leg mobility secondary to neuromuscular diseases or
      a bony fracture, impaired mental function, severe cardiopulmonary impairment, taking
      anticoagulants long-term, a history of intra-articular steroid injection in the prior 1 year,
      a history of knee injury involving ligaments and menisci, and a history of malignancy are
      excluded.

      All participants will be randomly divided into group A and group B. At the beginning of the
      study (T0), group A will receive one course of PRP+HA program and group B will receive one HA
      course (a single HA injection (Hyajoint) weekly for 3 weeks). The PRP+HA program includes 3
      HA injections and a single PRP injection (Arthrex double syringe system). In the 6th month,
      alternately, group B will receive one PRP+HA program and group A will receive one HA course.
      The study has 3 outcome assessment tools including a self-administered Western Ontario and
      McMaster Universities (WOMAC) Osteoarthritis Index, measurement of quadriceps strength with a
      digital handheld dynamometer, and measurement of femoral condylar cartilage thickness with
      musculoskeletal ultrasound. The investigators will conduct those assessments in the beginning
      (T0) of the study and the following 1st (T1), 3rd (T2), 6th (T3), and 9th (T4) months.

      In the 18th month following the beginning of the study, both groups will receive a booster
      course of PRP+HA program. During the first week of the program, group A will receive a HA
      injection before the PRP injection and group B will receive the HA injection after the PRP
      injection. The investigators will conduct the long-term assessments in the 12th (T5), 15th
      (T6), 18th (T7), and 21st (T8) months since the beginning of the study.
People aged >65 years are over 14% in Taiwan since the year 2018. Knee osteoarthritis (OA) is
      prevalent among elderly people. People with knee OA often have knee pain and stiffness as
      well as compromised their walking performance and quality of daily life. Although
      intra-articular knee injection with platelet-rich plasma (PRP) may have better outcomes than
      using hyaluronic acid (HA), it is expensive to use PRP. Programs with a combination of PRP
      and HA (PRP+HA) showed good results in vitro and animal studies. This 2-year study aims to
      clarify the short- and long-term effectiveness of the PRP+HA program for knee OA. The study
      will also assess the effectiveness of a booster course of PRP+HA program in the second year.

      The study will recruit 60 persons aged between 50 and 80 years who have experienced
      symptomatic knee OA for 6 months or more and have a radiographic picture of knee OA of grades
      1-3, based on the Kellegren-Lawrence scale. Those who have diabetes, fever, anemia (Hb <10
      g/dl), thrombocytopenia (platelet count <150000/ml), a blood-clotting disease, knee deformity
      (genu valgum/varum >20 degrees), impaired leg mobility secondary to neuromuscular diseases or
      a bony fracture, impaired mental function who have difficulty in completing outcome
      assessments, severe cardiopulmonary impairment, taking anticoagulants long-term, a history of
      intra-articular steroid injection in the prior 1 year, a history of knee injury involving
      ligaments and menisci, and a history of malignancy are excluded.

      All participants will be randomly divided into group A and group B. At the beginning of the
      study (T0), group A will receive one course of PRP+HA program and group B will receive one HA
      course (a single HA injection (Hyajoint) weekly for 3 weeks). The PRP+HA program includes 3
      HA injections and a single PRP injection (Arthrex double syringe system). In the 6th month,
      alternately, group B will receive one PRP+HA program and group A will receive one HA course.
      The study has 3 outcome assessment tools including a self-administered Western Ontario and
      McMaster Universities (WOMAC) Osteoarthritis Index, measurement of quadriceps strength with a
      digital handheld dynamometer, and measurement of femoral condylar cartilage thickness with
      musculoskeletal ultrasound. The investigators will conduct those assessments in the beginning
      (T0) of the study and the following 1st (T1), 3rd (T2), 6th (T3), and 9th (T4) months.

      In the 18th month following the beginning of the study, both groups will receive a booster
      course of PRP+HA program. During the first week of the program, group A will receive a HA
      injection before the PRP injection and group B will receive the HA injection after the PRP
      injection. The investigators will conduct the long-term assessments in the 12th (T5), 15th
      (T6), 18th (T7), and 21st (T8) months since the beginning of the study.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: Single (Outcomes Assessor)
measure: changes in WOMAC index
time frame: in the beginning (T0) of the study and the following 1st (T1), 3rd (T2), 6th (T3), 9th (T4), 12th (T5), 15th (T6), 18th (T7), and 21st (T8) months.
description: a self-administered Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index
measure: changes in quadriceps strength
time frame: in the beginning (T0) of the study and the following 1st (T1), 6th (T3), 12th (T5), 18th (T7), and 21st (T8) months.
description: measurement of quadriceps strength with a digital handheld dynamometer
measure: changes in cartilage thickness
time frame: in the beginning (T0) of the study and the following 1st (T1), 6th (T3), 12th (T5), 18th (T7), and 21st (T8) months.
description: measurement of femoral condylar cartilage thickness with musculoskeletal ultrasound
arm group label: Group A
arm group type: Experimental
description: At the beginning of the study (T0), group A will receive one course of PRP+HA program and group B will receive one HA course (a single HA injection (Hyajoint) weekly for 3 weeks). The PRP+HA program includes 3 HA injections and a single PRP injection (Arthrex double syringe system).
arm group label: Group B
arm group type: Active Comparator
description: In the 6th month, alternately, group B will receive one PRP+HA program and group A will receive one HA course.
intervention type: Combination Product
intervention name: A platelet-rich plasma (PRP)+ hyaluronic acid (HA) program
description: a combination of intra-articular knee injection with platelet-rich plasma (PRP) and hyaluronic acid (HA)
arm group label: Group A
arm group label: Group B
other name: A hyaluronic acid (HA) course (a single HA injection (Hyajoint) weekly for 3 weeks)
criteria: 
gender: All
minimum age: 50 Years
maximum age: 80 Years
healthy volunteers: No
last name: Kwang-Hwa Chang, MD
role: Principal Investigator
affiliation: Prof.
last name: Kwang-Hwa Chang, MD
phone: +886-2-29307930
phone ext: 1610
email: chang2773@gmail.com
responsible party type: Sponsor
mesh term: Osteoarthritis
mesh term: Osteoarthritis, Knee
mesh term: Hyaluronic Acid
sharing ipd: No