<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/NCT02993029</url>
  </required_header>
  <id_info>
    <org_study_id>osteoarthritis</org_study_id>
    <nct_id>NCT02993029</nct_id>
  </id_info>
  <brief_title>99Tc-MDP Treatment for Knee Osteoarthritis</brief_title>
  <official_title>99Tc-MDP Versus Celecoxib Treatment in Patients With Knee Osteoarthritis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Xinhua Hospital, Shanghai Jiao Tong University School of Medicine</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Xinhua Hospital, Shanghai Jiao Tong University School of Medicine</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Osteoarthritis (OA) of knee is the most common form of arthritis in the world1e, and it has&#xD;
      received growing attention in the society because of the increase of old age population,&#xD;
      disabled people, and medical expenses from this disease. 99Tc-MDP is effective for rheumatoid&#xD;
      arthritis. Therefore, the investigators try to investigate the effects of 99Tc-MDP treatment&#xD;
      in patients with osteoarthritis of knee as compared with celecoxib.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The prevalence of osteoarthritis of the knee (OA) is increasing worldwide and this burden&#xD;
      will continue to increase owing to aging of the general population 99Tc-MDP is effective for&#xD;
      rheumatoid arthritis. Consequent to an increase in incidence is the rise in the number of&#xD;
      patients with knee OA who are prone to further deterioration of the knee. It therefore is&#xD;
      important to better understand, control, and attempt to prevent further progression of&#xD;
      disease in patients with knee OA. Limitations in walking, stair climbing, and squatting are&#xD;
      common patient complaints that greatly interfere with activities of daily living and&#xD;
      recreation. Currently there is no definite consensus on the standardized management of OA.&#xD;
      Oral analgesic and anti-inflammatory agents are perhaps the most commonly prescribed&#xD;
      treatments to alleviate knee OA symptoms. The failure of nonsurgical therapies to modify&#xD;
      quality of life in knee OA patients is not surprising given their inability to alleviate&#xD;
      physical manifestations of OA. Surgical knee OA interventions generally result in good to&#xD;
      excellent patient outcomes. However, there are significant barriers to considering surgery,&#xD;
      which limits clinical utility.&#xD;
&#xD;
      99Tc-MDP is actually the decay product of 99mTc-MDP (99mTc-methylene diphosphonate, a US Food&#xD;
      and Drug Administration-approved radioactive agent widely used for bone scintigraphy).&#xD;
      99Tc-MDP (Chengdu Yunke Pharmaceutical, Sichuan, China) is a kind of anti-inflammatory drug&#xD;
      patented in China (patent no. ZL94113006.1). It was approved for production by the State Food&#xD;
      and Drug Administration of China in October 1997. 99Tc-MDP has been demonstrated to be safe&#xD;
      and effective in the clinical treatment of immune diseases, such as rheumatoid arthritis&#xD;
      (RA), ankylosing spondylitis (AS) and certain bone diseases, such as skeletal metastases from&#xD;
      cancer in China. 99Tc-MDP also showed clinical effect on knee OA in our practice. Therefore,&#xD;
      the investigators try to investigate the effects of 99Tc-MDP treatment in patients with&#xD;
      osteoarthritis of knee as compared with celecoxib.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">September 1, 2017</start_date>
  <completion_date type="Anticipated">December 30, 2023</completion_date>
  <primary_completion_date type="Anticipated">December 30, 2023</primary_completion_date>
  <phase>N/A</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>pain, stiffness and joint function of knee</measure>
    <time_frame>baseline, and 6, 12 months after treatment.</time_frame>
    <description>change of the pain, stiffness and joint function of knee (mean and standard deviation) by Western Ontario and McMaster Universities (WOMAC)Osteoarthritis Index</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>health-related quality of life</measure>
    <time_frame>baseline, and 6, 12 months after treatment.</time_frame>
    <description>change of health-related quality of life (mean and standard deviation) by SF-36</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>staging of knee osteoarthritisby</measure>
    <time_frame>baseline and 12 months after treatment.</time_frame>
    <description>number of participants who have change of knee osteoarthritis staging by X-ray or CT</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>standard uptake value of knee</measure>
    <time_frame>baseline and 12 months after treatment.</time_frame>
    <description>change of standard uptake value (SUV,mean and standard deviation) of knee on 18F- sodium fluoride or 99Tc-MDP bone scan and change of cystic area on according CT</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>adverse events</measure>
    <time_frame>3, 6, 12 months after treatment.</time_frame>
    <description>adverse events that are related to treatment</description>
  </secondary_outcome>
  <other_outcome>
    <measure>bone mineral density</measure>
    <time_frame>baseline and 12 months after treatment.</time_frame>
    <description>The changes of bone mineral density(mean and standard deviation) in lumbar and hip by a dual energy x-ray absorotiometrv</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">40</enrollment>
  <condition>Treatment Outcome</condition>
  <arm_group>
    <arm_group_label>99Tc-MDP</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>99Tc-MDP group:15mg in 100ml normal saline intravenously dripped every twice a week for 5 weeks, every 1weeks for 10 weeks, every 2weeks for 10 weeks, every 1 month for 6 months.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>celecoxib</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>celecoxib capsule 200mg qd by mouth.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>99Tc-MDP</intervention_name>
    <description>99Tc-MDP 15mg in 100ml normal saline intravenously dripped every twice a week for 5 weeks, every 1weeks for 10 weeks, every 2weeks for 10 weeks, every 1 month for 6 months.</description>
    <arm_group_label>99Tc-MDP</arm_group_label>
    <other_name>Yunke</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Celecoxib</intervention_name>
    <description>Celecoxib capsule 200mg qd by mouth.</description>
    <arm_group_label>celecoxib</arm_group_label>
    <other_name>Xile Bao</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Participants with painful osteoarthritis;&#xD;
&#xD;
          2. The standard uptake value (SUV) of OA related knee greater than 10 on 18F- sodium&#xD;
             fluoride bone scan;&#xD;
&#xD;
          3. Participants voluntarily participate in the trial, and signed the informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Knee joint replacement;&#xD;
&#xD;
          2. Inflammatory arthritis or joint infection of knee;&#xD;
&#xD;
          3. Nervous joint disease;&#xD;
&#xD;
          4. Fracture of joint;&#xD;
&#xD;
          5. Gout arthritis of the knee;&#xD;
&#xD;
          6. Traumatic arthritis.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>40 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Zhongwei Lv, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>The 10th Hospital, Tongji University</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Chao Ma, MD</last_name>
    <phone>+86-021-25078593</phone>
    <email>mc_7419@hotmail.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>Department of Nuclear Medicine, Tenth People's Hospital of Tongji University</name>
      <address>
        <city>Shanghai</city>
        <state>Shanghai</state>
        <zip>200072</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Chao Ma, MD</last_name>
      <phone>+86021-66302075</phone>
      <email>mc_7419@hotmail.com</email>
    </contact>
    <contact_backup>
      <last_name>Haidong Cai, MD</last_name>
      <phone>+86021-66302075</phone>
      <email>caihdong@163.com</email>
    </contact_backup>
    <investigator>
      <last_name>Yanlei Huo, BA</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Jianhao Huo, BA</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Danyang Wang, BA</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Jing Xu, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Kejia Gao, BA</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Haidong Cai, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <reference>
    <citation>Lai K, Xu L, Jin C, Wu K, Tian Z, Huang C, Zhong X, Ye H. Technetium-99 conjugated with methylene diphosphonate (99Tc-MDP) inhibits experimental choroidal neovascularization in vivo and VEGF-induced cell migration and tube formation in vitro. Invest Ophthalmol Vis Sci. 2011 Jul 29;52(8):5702-12. doi: 10.1167/iovs.10-6370.</citation>
    <PMID>21666238</PMID>
  </reference>
  <reference>
    <citation>Hochberg MC, Altman RD, April KT, Benkhalti M, Guyatt G, McGowan J, Towheed T, Welch V, Wells G, Tugwell P; American College of Rheumatology. American College of Rheumatology 2012 recommendations for the use of nonpharmacologic and pharmacologic therapies in osteoarthritis of the hand, hip, and knee. Arthritis Care Res (Hoboken). 2012 Apr;64(4):465-74. doi: 10.1002/acr.21596.</citation>
    <PMID>22563589</PMID>
  </reference>
  <reference>
    <citation>Boegard T, Rudling O, Dahlstrom J, Dirksen H, Petersson IF, Jonsson K. Bone scintigraphy in chronic knee pain: comparison with magnetic resonance imaging. Ann Rheum Dis. 1999 Jan;58(1):20-6. doi: 10.1136/ard.58.1.20.</citation>
    <PMID>10343536</PMID>
  </reference>
  <reference>
    <citation>Kim HR, So Y, Moon SG, Lee IS, Lee SH. Clinical value of (99m)Tc-methylene diphosphonate (MDP) bone single photon emission computed tomography (SPECT) in patients with knee osteoarthritis. Osteoarthritis Cartilage. 2008 Feb;16(2):212-8. doi: 10.1016/j.joca.2007.05.025. Epub 2007 Jul 27.</citation>
    <PMID>17662626</PMID>
  </reference>
  <reference>
    <citation>Liu H, Guo H, Guo S, Wang J, Ye Y, Ma C. Novel treatment of 99Tc-MDP improves clinical and radiographic results for patients with osteochondral lesions of the talus. Q J Nucl Med Mol Imaging. 2019 Jun;63(2):199-206. doi: 10.23736/S1824-4785.16.02872-7. Epub 2016 Jun 21.</citation>
    <PMID>27327630</PMID>
  </reference>
  <results_reference>
    <citation>McCrae F, Shouls J, Dieppe P, Watt I. Scintigraphic assessment of osteoarthritis of the knee joint. Ann Rheum Dis. 1992 Aug;51(8):938-42. doi: 10.1136/ard.51.8.938.</citation>
    <PMID>1417117</PMID>
  </results_reference>
  <verification_date>October 2022</verification_date>
  <study_first_submitted>December 8, 2016</study_first_submitted>
  <study_first_submitted_qc>December 12, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 14, 2016</study_first_posted>
  <last_update_submitted>October 24, 2022</last_update_submitted>
  <last_update_submitted_qc>October 24, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">October 26, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Xinhua Hospital, Shanghai Jiao Tong University School of Medicine</investigator_affiliation>
    <investigator_full_name>Chao Ma</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <keyword>99Tc-MDP</keyword>
  <keyword>osteoarthritis</keyword>
  <keyword>celecoxib</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>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Celecoxib</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/NCT02993029
org study id: osteoarthritis
nct id: NCT02993029
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Osteoarthritis (OA) of knee is the most common form of arthritis in the world1e, and it has
      received growing attention in the society because of the increase of old age population,
      disabled people, and medical expenses from this disease. 99Tc-MDP is effective for rheumatoid
      arthritis. Therefore, the investigators try to investigate the effects of 99Tc-MDP treatment
      in patients with osteoarthritis of knee as compared with celecoxib.
The prevalence of osteoarthritis of the knee (OA) is increasing worldwide and this burden
      will continue to increase owing to aging of the general population 99Tc-MDP is effective for
      rheumatoid arthritis. Consequent to an increase in incidence is the rise in the number of
      patients with knee OA who are prone to further deterioration of the knee. It therefore is
      important to better understand, control, and attempt to prevent further progression of
      disease in patients with knee OA. Limitations in walking, stair climbing, and squatting are
      common patient complaints that greatly interfere with activities of daily living and
      recreation. Currently there is no definite consensus on the standardized management of OA.
      Oral analgesic and anti-inflammatory agents are perhaps the most commonly prescribed
      treatments to alleviate knee OA symptoms. The failure of nonsurgical therapies to modify
      quality of life in knee OA patients is not surprising given their inability to alleviate
      physical manifestations of OA. Surgical knee OA interventions generally result in good to
      excellent patient outcomes. However, there are significant barriers to considering surgery,
      which limits clinical utility.

      99Tc-MDP is actually the decay product of 99mTc-MDP (99mTc-methylene diphosphonate, a US Food
      and Drug Administration-approved radioactive agent widely used for bone scintigraphy).
      99Tc-MDP (Chengdu Yunke Pharmaceutical, Sichuan, China) is a kind of anti-inflammatory drug
      patented in China (patent no. ZL94113006.1). It was approved for production by the State Food
      and Drug Administration of China in October 1997. 99Tc-MDP has been demonstrated to be safe
      and effective in the clinical treatment of immune diseases, such as rheumatoid arthritis
      (RA), ankylosing spondylitis (AS) and certain bone diseases, such as skeletal metastases from
      cancer in China. 99Tc-MDP also showed clinical effect on knee OA in our practice. Therefore,
      the investigators try to investigate the effects of 99Tc-MDP treatment in patients with
      osteoarthritis of knee as compared with celecoxib.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: pain, stiffness and joint function of knee
time frame: baseline, and 6, 12 months after treatment.
description: change of the pain, stiffness and joint function of knee (mean and standard deviation) by Western Ontario and McMaster Universities (WOMAC)Osteoarthritis Index
measure: health-related quality of life
time frame: baseline, and 6, 12 months after treatment.
description: change of health-related quality of life (mean and standard deviation) by SF-36
measure: staging of knee osteoarthritisby
time frame: baseline and 12 months after treatment.
description: number of participants who have change of knee osteoarthritis staging by X-ray or CT
measure: standard uptake value of knee
time frame: baseline and 12 months after treatment.
description: change of standard uptake value (SUV,mean and standard deviation) of knee on 18F- sodium fluoride or 99Tc-MDP bone scan and change of cystic area on according CT
measure: adverse events
time frame: 3, 6, 12 months after treatment.
description: adverse events that are related to treatment
measure: bone mineral density
time frame: baseline and 12 months after treatment.
description: The changes of bone mineral density(mean and standard deviation) in lumbar and hip by a dual energy x-ray absorotiometrv
arm group label: 99Tc-MDP
arm group type: Experimental
description: 99Tc-MDP group:15mg in 100ml normal saline intravenously dripped every twice a week for 5 weeks, every 1weeks for 10 weeks, every 2weeks for 10 weeks, every 1 month for 6 months.
arm group label: celecoxib
arm group type: Active Comparator
description: celecoxib capsule 200mg qd by mouth.
intervention type: Drug
intervention name: 99Tc-MDP
description: 99Tc-MDP 15mg in 100ml normal saline intravenously dripped every twice a week for 5 weeks, every 1weeks for 10 weeks, every 2weeks for 10 weeks, every 1 month for 6 months.
arm group label: 99Tc-MDP
other name: Yunke
intervention type: Drug
intervention name: Celecoxib
description: Celecoxib capsule 200mg qd by mouth.
arm group label: celecoxib
other name: Xile Bao
criteria: 
gender: All
minimum age: 40 Years
maximum age: N/A
healthy volunteers: No
last name: Zhongwei Lv, MD
role: Principal Investigator
affiliation: The 10th Hospital, Tongji University
last name: Chao Ma, MD
phone: +86-021-25078593
email: mc_7419@hotmail.com
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
country: China
citation: Lai K, Xu L, Jin C, Wu K, Tian Z, Huang C, Zhong X, Ye H. Technetium-99 conjugated with methylene diphosphonate (99Tc-MDP) inhibits experimental choroidal neovascularization in vivo and VEGF-induced cell migration and tube formation in vitro. Invest Ophthalmol Vis Sci. 2011 Jul 29;52(8):5702-12. doi: 10.1167/iovs.10-6370.
PMID: 21666238
citation: Hochberg MC, Altman RD, April KT, Benkhalti M, Guyatt G, McGowan J, Towheed T, Welch V, Wells G, Tugwell P; American College of Rheumatology. American College of Rheumatology 2012 recommendations for the use of nonpharmacologic and pharmacologic therapies in osteoarthritis of the hand, hip, and knee. Arthritis Care Res (Hoboken). 2012 Apr;64(4):465-74. doi: 10.1002/acr.21596.
PMID: 22563589
citation: Boegard T, Rudling O, Dahlstrom J, Dirksen H, Petersson IF, Jonsson K. Bone scintigraphy in chronic knee pain: comparison with magnetic resonance imaging. Ann Rheum Dis. 1999 Jan;58(1):20-6. doi: 10.1136/ard.58.1.20.
PMID: 10343536
citation: Kim HR, So Y, Moon SG, Lee IS, Lee SH. Clinical value of (99m)Tc-methylene diphosphonate (MDP) bone single photon emission computed tomography (SPECT) in patients with knee osteoarthritis. Osteoarthritis Cartilage. 2008 Feb;16(2):212-8. doi: 10.1016/j.joca.2007.05.025. Epub 2007 Jul 27.
PMID: 17662626
citation: Liu H, Guo H, Guo S, Wang J, Ye Y, Ma C. Novel treatment of 99Tc-MDP improves clinical and radiographic results for patients with osteochondral lesions of the talus. Q J Nucl Med Mol Imaging. 2019 Jun;63(2):199-206. doi: 10.23736/S1824-4785.16.02872-7. Epub 2016 Jun 21.
PMID: 27327630
citation: McCrae F, Shouls J, Dieppe P, Watt I. Scintigraphic assessment of osteoarthritis of the knee joint. Ann Rheum Dis. 1992 Aug;51(8):938-42. doi: 10.1136/ard.51.8.938.
PMID: 1417117
responsible party type: Principal Investigator
investigator affiliation: Xinhua Hospital, Shanghai Jiao Tong University School of Medicine
investigator full name: Chao Ma
investigator title: Professor
mesh term: Osteoarthritis
mesh term: Osteoarthritis, Knee
mesh term: Celecoxib
sharing ipd: No