<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/NCT03279796</url>
  </required_header>
  <id_info>
    <org_study_id>2017.No.55</org_study_id>
    <nct_id>NCT03279796</nct_id>
  </id_info>
  <brief_title>Treatment of Tendon Disease Using Autologous Adipose-derived Mesenchymal Stem Cells</brief_title>
  <official_title>Autologous Adipose-derived Mesenchymal Stem Cells in the Treatment of Tendon Disease: a Randomized Controlled Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Second Affiliated Hospital, School of Medicine, Zhejiang University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Zhejiang Xingyue Biotechnology Co., Ltd.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Second Affiliated Hospital, School of Medicine, Zhejiang University</source>
  <oversight_info>
    <has_dmc>No</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>
      This study was a single-center, randomized, single-blind clinical trial. We plan to include&#xD;
      100 patients who met exclusion criteria of rotator cuff and lateral epicondylosis (tennis&#xD;
      elbow) respectively by MRT or ultrasonography. The patients will be randomly divided into two&#xD;
      groups. Adipose mesenchymal stem cells will be isolated from adipose tissue, cultured and&#xD;
      then transplanted back to the tendon injury site by multiple point injection. 1*10^6 cells as&#xD;
      an unit. Patients in the experiment group will be injected into an unit of adipose&#xD;
      mesenchymal stem cells (1*10^6/10kg) while the control group received the same dose compound&#xD;
      betamethasone injection. Follow up visit for all patients will occur at 1，3，6 and 12 months&#xD;
      after the first injection. Clinical quantitative assessment will measure by the visual&#xD;
      analogue scale(VAS). The secondary outcomes are the constant-murley score(CMS) and the rating&#xD;
      scale of the American shoulder and elbow surgeons(ASES) and the disability of arm shoulder&#xD;
      and hand(DASH). The objective evaluation methods is that the examination of MRI or ultrasound&#xD;
      were accomplished before the first injection and at 6 and 12 months afterwards.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      All injection will be done under ultrasound guidance.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date type="Anticipated">October 1, 2018</start_date>
  <completion_date type="Anticipated">December 31, 2021</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2019</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Participant)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change from baseline in Visual Analog Scale(VAS) at 3, 6 and 12 weeks</measure>
    <time_frame>Baseline, 3 weeks, 6 weeks, 12 weeks after intervention</time_frame>
    <description>Pain on activity will be evaluated by VAS</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in Constant-Murley Score(CMS) at 3, 6 and 12 weeks,</measure>
    <time_frame>Baseline, 3 weeks, 6 weeks, 12 weeks after intervention</time_frame>
    <description>Functional score of the shoulder</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>American Shoulder and Elbow Surgeons (ASES) Shoulder Score</measure>
    <time_frame>Baseline, 3 weeks, 6 weeks, 12 weeks after intervention</time_frame>
    <description>Functional score of the shoulder</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The Disabilities of the Arm, Shoulder and Hand(DASH) Score</measure>
    <time_frame>Baseline, 3 weeks, 6 weeks, 12 weeks after intervention</time_frame>
    <description>Functional score of the shoulder</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse events</measure>
    <time_frame>From baseline through study completion, an average of 1 year</time_frame>
    <description>Adverse events to evaluate the safety</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">200</enrollment>
  <condition>Rotator Cuff Tear</condition>
  <condition>Lateral Epicondylitis</condition>
  <arm_group>
    <arm_group_label>Autologous adipose-derived MSCs</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The dose of adipose-derived mesenchymal stem cells was related to body weight, and 1 × 10 ^ 6 cells were a unit. One unit of adipose-derived mesenchymal stem cells was injected every 10 kg of body weight and injected once a week for three times.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Compound betamethasone</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>1ml dexamethasone mixed with 0.5-2ml of saline to achieve the same injection volume with the cell suspension (which contains betamethasone dipropionate 5mg and betamethasone sodium phosphate 2mg) ), once a week for three times.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Autologous adipose-derived MSCs</intervention_name>
    <description>The dose of adipose-derived mesenchymal stem cells was related to body weight, and 1 × 10 ^ 6 cells were a unit. One unit of adipose-derived mesenchymal stem cells was injected every 10 kg of body weight and injected once a week for three times.</description>
    <arm_group_label>Autologous adipose-derived MSCs</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Compound betamethasone</intervention_name>
    <description>1ml dexamethasone mixed with 0.5-2ml of saline to achieve the same injection volume with the cell suspension (which contains betamethasone dipropionate 5mg and betamethasone sodium phosphate 2mg) ), once a week for three times.</description>
    <arm_group_label>Compound betamethasone</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. clinically diagnosed as rotator cuff tear or lateral epicondylitis (tennis elbow);&#xD;
&#xD;
          2. symptom duration is over 3 months, non-steroidal drug treatment , rehabilitation&#xD;
             treatment and other conservative treatment is invalid;&#xD;
&#xD;
          3. patient that can understand the clinical trials and signed the informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. patient that underwent other injection treatment within 6 weeks&#xD;
&#xD;
          2. some associated diseases (such as arthritis, synovitis, entrapment of related nerve,&#xD;
             radiculopathy to the target lesion, generalized pain syndrome, rheumatoid arthritis,&#xD;
             pregnancy, impaired sensibility, paralysis, history of allergic or hypersensitive&#xD;
             reaction to bovine-derived proteins or fibrin glue)&#xD;
&#xD;
          3. patient that enrolled other clinical trials within 3 months&#xD;
&#xD;
          4. history of drug/alcohol addiction, habitual smoker&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>90 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Weiliang Shen, Doctor</last_name>
    <phone>+86-13757101563</phone>
    <email>wlshen@zju.edu.cn</email>
  </overall_contact>
  <location>
    <facility>
      <name>Weiliang Shen</name>
      <address>
        <city>Hangzhou</city>
        <state>Zhejiang</state>
        <zip>310058</zip>
        <country>China</country>
      </address>
    </facility>
    <contact>
      <last_name>Weiliang Shen, Doctor</last_name>
    </contact>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <reference>
    <citation>Ellera Gomes JL, da Silva RC, Silla LM, Abreu MR, Pellanda R. Conventional rotator cuff repair complemented by the aid of mononuclear autologous stem cells. Knee Surg Sports Traumatol Arthrosc. 2012 Feb;20(2):373-7. doi: 10.1007/s00167-011-1607-9. Epub 2011 Jul 20.</citation>
    <PMID>21773831</PMID>
  </reference>
  <reference>
    <citation>Pascual-Garrido C, Rolon A, Makino A. Treatment of chronic patellar tendinopathy with autologous bone marrow stem cells: a 5-year-followup. Stem Cells Int. 2012;2012:953510. doi: 10.1155/2012/953510. Epub 2011 Dec 18.</citation>
    <PMID>22220180</PMID>
  </reference>
  <reference>
    <citation>Hernigou P, Flouzat Lachaniette CH, Delambre J, Zilber S, Duffiet P, Chevallier N, Rouard H. Biologic augmentation of rotator cuff repair with mesenchymal stem cells during arthroscopy improves healing and prevents further tears: a case-controlled study. Int Orthop. 2014 Sep;38(9):1811-8. doi: 10.1007/s00264-014-2391-1. Epub 2014 Jun 7.</citation>
    <PMID>24913770</PMID>
  </reference>
  <reference>
    <citation>Pas HIMFL, Moen MH, Haisma HJ, Winters M. No evidence for the use of stem cell therapy for tendon disorders: a systematic review. Br J Sports Med. 2017 Jul;51(13):996-1002. doi: 10.1136/bjsports-2016-096794. Epub 2017 Jan 11.</citation>
    <PMID>28077355</PMID>
  </reference>
  <reference>
    <citation>Lee SY, Kim W, Lim C, Chung SG. Treatment of Lateral Epicondylosis by Using Allogeneic Adipose-Derived Mesenchymal Stem Cells: A Pilot Study. Stem Cells. 2015 Oct;33(10):2995-3005. doi: 10.1002/stem.2110. Epub 2015 Aug 6.</citation>
    <PMID>26202898</PMID>
  </reference>
  <reference>
    <citation>Ouyang HW, Goh JC, Thambyah A, Teoh SH, Lee EH. Knitted poly-lactide-co-glycolide scaffold loaded with bone marrow stromal cells in repair and regeneration of rabbit Achilles tendon. Tissue Eng. 2003 Jun;9(3):431-9. doi: 10.1089/107632703322066615.</citation>
    <PMID>12857411</PMID>
  </reference>
  <reference>
    <citation>Minagawa H, Yamamoto N, Abe H, Fukuda M, Seki N, Kikuchi K, Kijima H, Itoi E. Prevalence of symptomatic and asymptomatic rotator cuff tears in the general population: From mass-screening in one village. J Orthop. 2013 Feb 26;10(1):8-12. doi: 10.1016/j.jor.2013.01.008. eCollection 2013.</citation>
    <PMID>24403741</PMID>
  </reference>
  <verification_date>August 2017</verification_date>
  <study_first_submitted>September 4, 2017</study_first_submitted>
  <study_first_submitted_qc>September 10, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 12, 2017</study_first_posted>
  <last_update_submitted>April 24, 2018</last_update_submitted>
  <last_update_submitted_qc>April 24, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">April 26, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Adipose-drived mesenchymal stem cells</keyword>
  <keyword>Rotator cuff injury</keyword>
  <keyword>Lateral Epicondylitis</keyword>
  <keyword>Randomized controlled trials</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Tennis Elbow</mesh_term>
    <mesh_term>Rotator Cuff Injuries</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Betamethasone</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/NCT03279796
org study id: 2017.No.55
nct id: NCT03279796
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This study was a single-center, randomized, single-blind clinical trial. We plan to include
      100 patients who met exclusion criteria of rotator cuff and lateral epicondylosis (tennis
      elbow) respectively by MRT or ultrasonography. The patients will be randomly divided into two
      groups. Adipose mesenchymal stem cells will be isolated from adipose tissue, cultured and
      then transplanted back to the tendon injury site by multiple point injection. 1*10^6 cells as
      an unit. Patients in the experiment group will be injected into an unit of adipose
      mesenchymal stem cells (1*10^6/10kg) while the control group received the same dose compound
      betamethasone injection. Follow up visit for all patients will occur at 1，3，6 and 12 months
      after the first injection. Clinical quantitative assessment will measure by the visual
      analogue scale(VAS). The secondary outcomes are the constant-murley score(CMS) and the rating
      scale of the American shoulder and elbow surgeons(ASES) and the disability of arm shoulder
      and hand(DASH). The objective evaluation methods is that the examination of MRI or ultrasound
      were accomplished before the first injection and at 6 and 12 months afterwards.
All injection will be done under ultrasound guidance.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Participant)
measure: Change from baseline in Visual Analog Scale(VAS) at 3, 6 and 12 weeks
time frame: Baseline, 3 weeks, 6 weeks, 12 weeks after intervention
description: Pain on activity will be evaluated by VAS
measure: Change from baseline in Constant-Murley Score(CMS) at 3, 6 and 12 weeks,
time frame: Baseline, 3 weeks, 6 weeks, 12 weeks after intervention
description: Functional score of the shoulder
measure: American Shoulder and Elbow Surgeons (ASES) Shoulder Score
time frame: Baseline, 3 weeks, 6 weeks, 12 weeks after intervention
description: Functional score of the shoulder
measure: The Disabilities of the Arm, Shoulder and Hand(DASH) Score
time frame: Baseline, 3 weeks, 6 weeks, 12 weeks after intervention
description: Functional score of the shoulder
measure: Adverse events
time frame: From baseline through study completion, an average of 1 year
description: Adverse events to evaluate the safety
arm group label: Autologous adipose-derived MSCs
arm group type: Experimental
description: The dose of adipose-derived mesenchymal stem cells was related to body weight, and 1 × 10 ^ 6 cells were a unit. One unit of adipose-derived mesenchymal stem cells was injected every 10 kg of body weight and injected once a week for three times.
arm group label: Compound betamethasone
arm group type: Active Comparator
description: 1ml dexamethasone mixed with 0.5-2ml of saline to achieve the same injection volume with the cell suspension (which contains betamethasone dipropionate 5mg and betamethasone sodium phosphate 2mg) ), once a week for three times.
intervention type: Biological
intervention name: Autologous adipose-derived MSCs
description: The dose of adipose-derived mesenchymal stem cells was related to body weight, and 1 × 10 ^ 6 cells were a unit. One unit of adipose-derived mesenchymal stem cells was injected every 10 kg of body weight and injected once a week for three times.
arm group label: Autologous adipose-derived MSCs
intervention type: Drug
intervention name: Compound betamethasone
description: 1ml dexamethasone mixed with 0.5-2ml of saline to achieve the same injection volume with the cell suspension (which contains betamethasone dipropionate 5mg and betamethasone sodium phosphate 2mg) ), once a week for three times.
arm group label: Compound betamethasone
criteria: 
gender: All
minimum age: 18 Years
maximum age: 90 Years
healthy volunteers: No
last name: Weiliang Shen, Doctor
phone: +86-13757101563
email: wlshen@zju.edu.cn
facility: 
contact: 
country: China
citation: Ellera Gomes JL, da Silva RC, Silla LM, Abreu MR, Pellanda R. Conventional rotator cuff repair complemented by the aid of mononuclear autologous stem cells. Knee Surg Sports Traumatol Arthrosc. 2012 Feb;20(2):373-7. doi: 10.1007/s00167-011-1607-9. Epub 2011 Jul 20.
PMID: 21773831
citation: Pascual-Garrido C, Rolon A, Makino A. Treatment of chronic patellar tendinopathy with autologous bone marrow stem cells: a 5-year-followup. Stem Cells Int. 2012;2012:953510. doi: 10.1155/2012/953510. Epub 2011 Dec 18.
PMID: 22220180
citation: Hernigou P, Flouzat Lachaniette CH, Delambre J, Zilber S, Duffiet P, Chevallier N, Rouard H. Biologic augmentation of rotator cuff repair with mesenchymal stem cells during arthroscopy improves healing and prevents further tears: a case-controlled study. Int Orthop. 2014 Sep;38(9):1811-8. doi: 10.1007/s00264-014-2391-1. Epub 2014 Jun 7.
PMID: 24913770
citation: Pas HIMFL, Moen MH, Haisma HJ, Winters M. No evidence for the use of stem cell therapy for tendon disorders: a systematic review. Br J Sports Med. 2017 Jul;51(13):996-1002. doi: 10.1136/bjsports-2016-096794. Epub 2017 Jan 11.
PMID: 28077355
citation: Lee SY, Kim W, Lim C, Chung SG. Treatment of Lateral Epicondylosis by Using Allogeneic Adipose-Derived Mesenchymal Stem Cells: A Pilot Study. Stem Cells. 2015 Oct;33(10):2995-3005. doi: 10.1002/stem.2110. Epub 2015 Aug 6.
PMID: 26202898
citation: Ouyang HW, Goh JC, Thambyah A, Teoh SH, Lee EH. Knitted poly-lactide-co-glycolide scaffold loaded with bone marrow stromal cells in repair and regeneration of rabbit Achilles tendon. Tissue Eng. 2003 Jun;9(3):431-9. doi: 10.1089/107632703322066615.
PMID: 12857411
citation: Minagawa H, Yamamoto N, Abe H, Fukuda M, Seki N, Kikuchi K, Kijima H, Itoi E. Prevalence of symptomatic and asymptomatic rotator cuff tears in the general population: From mass-screening in one village. J Orthop. 2013 Feb 26;10(1):8-12. doi: 10.1016/j.jor.2013.01.008. eCollection 2013.
PMID: 24403741
responsible party type: Sponsor
mesh term: Tennis Elbow
mesh term: Rotator Cuff Injuries
mesh term: Betamethasone
sharing ipd: No