<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/NCT04414592</url>
  </required_header>
  <id_info>
    <org_study_id>QFu</org_study_id>
    <nct_id>NCT04414592</nct_id>
  </id_info>
  <brief_title>Human Umbilical Cord Mesenchymal Stem Cells For the Treatment of Lumbar Disc Degeneration Disease</brief_title>
  <official_title>Safety and Effectiveness of Human Umbilical Cord Mesenchymal Stem Cells For the Treatment of Lumbar Disc Degeneration Disease</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Shanghai General 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>
      This study aims to investigate the safety and efficiency of Human Umbilical Cord Mesenchymal&#xD;
      Stem Cells (hUCMSC) for treating lumbar disc degeneration diseases. We hypothesize grafting&#xD;
      hUCMSC into the degenerative disc leads to symptoms relief and slow down the progression of&#xD;
      disc degeneration.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Lumbar disc herniation causes patients severe lower back pain and radicular pain to decrease&#xD;
      the quality of life and lead to great economic burden to patients and society. In recent&#xD;
      years, full endoscopic discectomy has been widely used in the treatment of lumbar disc&#xD;
      herniation due to its advantages of reduced trauma, enhanced recovery and less cost. However,&#xD;
      the reherniation of the residual nucleus pulposus still exist after nerve root decompression.&#xD;
      It is urgent to use stem cell and tissue engineering to replace the resection tissue and&#xD;
      repair the residual nucleus pulposus for disc resealing. To observe the safety and efficacy&#xD;
      of human umbilical cord mesenchymal stem cells (hUCMSCs) in the treatment of lumbar disc&#xD;
      degeneration. This clinical trial is aimed to include a single group of 20 patients with&#xD;
      lumbar disc herniation. Twenty million hUCMSCs will be injected into the lumbar disc of the&#xD;
      enrolled patients in this non-random, self-controlled and single-dose open study design. The&#xD;
      patients will be followed up for 3 months, 6 months and 12 months after the injection to&#xD;
      evaluate the safety of the patients after grafting hUCMSCs. Additionally, improvement of&#xD;
      patients' quality of life will be evaluated using the ODI score, VAS score and SF-36 score.&#xD;
      Lumbar disc signals will be also quantified using MRI to demonstrate hUCMSCs transplantation&#xD;
      could slow down lumbar disc degeneration.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Anticipated">August 2020</start_date>
  <completion_date type="Anticipated">March 2023</completion_date>
  <primary_completion_date type="Anticipated">March 2022</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Lumbar disc signaling values from magnetic resonance imaging</measure>
    <time_frame>Baseline, post-op 3months, post-op 6months, post-op 12months</time_frame>
    <description>Changes from baseline in Lumbar disc signaling values from magnetic resonance imaging</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Visual Analogue Scale (VAS) (0-10 scores, the higher scores mean a worse outcome)</measure>
    <time_frame>Baseline, post-op 3months, post-op 6months, post-op 12months</time_frame>
    <description>Changes from baseline in Visual Analogue Scale of Lower back pain and leg pain</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Oswestry Disability Index(ODI) (0-50 scores, the higher scores mean a worse outcome)</measure>
    <time_frame>Baseline, post-op 3months, post-op 6months, post-op 12months</time_frame>
    <description>Changes from baseline in Oswestry Disability Index</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The Short Form (36) Health survey (SF36) (0-100 scores, the higher scores mean a better outcome)</measure>
    <time_frame>Baseline, post-op 3months, post-op 6months, post-op 12months</time_frame>
    <description>Changes from baseline in The Short Form (36) Health survey (SF36)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disc Height Index (DHI) from X ray</measure>
    <time_frame>Baseline, post-op 3months, post-op 6months, post-op 12months</time_frame>
    <description>Changes from baseline in Disc Height Index</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Size of herniated nucleus pulposus from magnetic resonance imaging</measure>
    <time_frame>Baseline, post-op 3months, post-op 6months, post-op 12months</time_frame>
    <description>Changes from baseline in size of nucleus pulposus from magnetic resonance imaging</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of participants with treatment-related adverse events by CTCAE v4.0</measure>
    <time_frame>From baseline until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 12 months</time_frame>
    <description>Assessing for worsening of patients' baseline symptoms or functions (will be considered an AE); (also general AE events), particular AE events related to the procedures/treatment. All AEs will be assessed by common terminology criteria for adverse events.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">20</enrollment>
  <condition>Lumbar Disc Degeneration</condition>
  <condition>Lumbar Disc Herniation</condition>
  <arm_group>
    <arm_group_label>Human Umbilical Cord Mesenchymal Stem Cells</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Injection of twenty million human umbilical cord mesenchymal stem cells into the degenerative disc</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>human umbilical cord mesenchymal stem cells</intervention_name>
    <description>Twenty million human umbilical cord mesenchymal stem cells will be immediately injected into the degenerative discs of such patients who are diagnosed with lumbar disc herniation and operated with full endoscopy lumbar discectomy.</description>
    <arm_group_label>Human Umbilical Cord Mesenchymal Stem Cells</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Age: 18-60 years old;&#xD;
&#xD;
          2. Symptoms with lower back pain and unilateral radicular pain;&#xD;
&#xD;
          3. Failure of conservative treatments including physical therapy, manipulation therapy&#xD;
             and non-morphine drug therapy;&#xD;
&#xD;
          4. CT/MRI clearly showing unilateral nucleus pulposus herniation to compress the nerve&#xD;
             root;&#xD;
&#xD;
          5. Symptoms and imaging showing unilateral lumbar disc herniation;&#xD;
&#xD;
          6. Imaging showed single-segment lumbar disc herniation;&#xD;
&#xD;
          7. Pfirrmann disc degeneration classification from lumbar MRI: grade I-IV;&#xD;
&#xD;
          8. Segments of lumbar disc herniation: L3-4, L4-5, L5-S1;&#xD;
&#xD;
          9. Unilateral full endoscopic lumbar discectomy;&#xD;
&#xD;
         10. Signing the informed consent;&#xD;
&#xD;
         11. No previous history of spinal surgery.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Previous history of tumor or spinal infection;&#xD;
&#xD;
          2. Severe coagulation disorders or are taking oral anticoagulants&#xD;
&#xD;
          3. coma or incapacity;&#xD;
&#xD;
          4. MRI contraindications (cardiovascular and cerebrovascular stent implantation history,&#xD;
             cardiac pacemaker, biological stimulator, etc.);&#xD;
&#xD;
          5. pregnant;&#xD;
&#xD;
          6. pregnancy or breastfeeding;&#xD;
&#xD;
          7. participated in other clinical trials in the past 30 days;&#xD;
&#xD;
          8. History of stem cell therapy;&#xD;
&#xD;
          9. poor compliance, or inability to properly understand the coordination;&#xD;
&#xD;
         10. received intervertebral disc interventional therapy, such as radiofrequency, laser&#xD;
             ablation, protease injection and ozone injection in the past 3 months;&#xD;
&#xD;
         11. Highly allergic constitution or severe allergic history;&#xD;
&#xD;
         12. Severe autoimmune diseases or receiving immunosuppressive therapy;&#xD;
&#xD;
         13. Severe infection or high fever;&#xD;
&#xD;
         14. Shock, failure of vital organs or unstable vital signs;&#xD;
&#xD;
         15. X-ray showing that the stenosis percentage of the degenerative segment was larger than&#xD;
             30% compared to that of the adjacent normal segment.&#xD;
&#xD;
         16. Lumbar disc herniation with calcification;&#xD;
&#xD;
         17. Lumbar disc herniation with Modic Change;&#xD;
&#xD;
         18. Lumbar disc herniation with severe spinal stenosis;&#xD;
&#xD;
         19. Lumbar disc herniation with lumbar spondylolisthesis;&#xD;
&#xD;
         20. Lumbar disc herniation with spinal deformity;&#xD;
&#xD;
         21. psychosocial abnormalities, cognitive impairment, or other physical diseases affecting&#xD;
             the research results;&#xD;
&#xD;
         22. Other reasons.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Qiang Fu, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Minimally Invasive Spinal of Shanghai General Hospital</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Song Guo, M.D.</last_name>
    <phone>15901836457</phone>
    <email>guosongtj@163.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Jigang Zhang, M.D.</last_name>
    <phone>18621155781</phone>
    <email>2293259778@qq.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Shanghai General Hospital</name>
      <address>
        <city>Shanghai</city>
        <state>Shanghai</state>
        <zip>200080</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Qiang Fu, M.D.</last_name>
      <phone>13636636288</phone>
      <email>johson.f@163.com</email>
    </contact>
    <contact_backup>
      <last_name>Song Guo, M.D.</last_name>
      <phone>15901836457</phone>
      <email>guosongtj@163.com</email>
    </contact_backup>
    <investigator>
      <last_name>Qiang Fu, M.D.</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Shanghai General Hospital</name>
      <address>
        <city>Shanghai</city>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Qiang Fu, M.D.</last_name>
      <phone>13636636288</phone>
    </contact>
    <investigator>
      <last_name>Qiang Fu, M.D.</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <reference>
    <citation>Walker BF. The prevalence of low back pain: a systematic review of the literature from 1966 to 1998. J Spinal Disord. 2000 Jun;13(3):205-17. doi: 10.1097/00002517-200006000-00003.</citation>
    <PMID>10872758</PMID>
  </reference>
  <reference>
    <citation>Ghiselli G, Wang JC, Bhatia NN, Hsu WK, Dawson EG. Adjacent segment degeneration in the lumbar spine. J Bone Joint Surg Am. 2004 Jul;86(7):1497-503. doi: 10.2106/00004623-200407000-00020.</citation>
    <PMID>15252099</PMID>
  </reference>
  <reference>
    <citation>Chen Z, Zhang L, Dong J, Xie P, Liu B, Wang Q, Chen R, Shu T, Li S, Feng F, Yang B, He L, Yang Y, Liu Z, Pang M, Rong L. Percutaneous Transforaminal Endoscopic Discectomy Versus Microendoscopic Discectomy for Lumbar Disc Herniation: Two-Year Results of a Randomized Controlled Trial. Spine (Phila Pa 1976). 2020 Apr 15;45(8):493-503. doi: 10.1097/BRS.0000000000003314.</citation>
    <PMID>31703056</PMID>
  </reference>
  <reference>
    <citation>Li Z, Lang G, Chen X, Sacks H, Mantzur C, Tropp U, Mader KT, Smallwood TC, Sammon C, Richards RG, Alini M, Grad S. Polyurethane scaffold with in situ swelling capacity for nucleus pulposus replacement. Biomaterials. 2016 Apr;84:196-209. doi: 10.1016/j.biomaterials.2016.01.040. Epub 2016 Jan 21.</citation>
    <PMID>26828684</PMID>
  </reference>
  <reference>
    <citation>Moriguchi Y, Mojica-Santiago J, Grunert P, Pennicooke B, Berlin C, Khair T, Navarro-Ramirez R, Ricart Arbona RJ, Nguyen J, Hartl R, Bonassar LJ. Total disc replacement using tissue-engineered intervertebral discs in the canine cervical spine. PLoS One. 2017 Oct 20;12(10):e0185716. doi: 10.1371/journal.pone.0185716. eCollection 2017.</citation>
    <PMID>29053719</PMID>
  </reference>
  <reference>
    <citation>Benneker LM, Andersson G, Iatridis JC, Sakai D, Hartl R, Ito K, Grad S. Cell therapy for intervertebral disc repair: advancing cell therapy from bench to clinics. Eur Cell Mater. 2014 May 6;27:5-11. doi: 10.22203/ecm.v027sa02.</citation>
    <PMID>24802611</PMID>
  </reference>
  <reference>
    <citation>Sobajima S, Vadala G, Shimer A, Kim JS, Gilbertson LG, Kang JD. Feasibility of a stem cell therapy for intervertebral disc degeneration. Spine J. 2008 Nov-Dec;8(6):888-96. doi: 10.1016/j.spinee.2007.09.011. Epub 2007 Dec 21.</citation>
    <PMID>18082460</PMID>
  </reference>
  <reference>
    <citation>Sakai D, Mochida J, Yamamoto Y, Nomura T, Okuma M, Nishimura K, Nakai T, Ando K, Hotta T. Transplantation of mesenchymal stem cells embedded in Atelocollagen gel to the intervertebral disc: a potential therapeutic model for disc degeneration. Biomaterials. 2003 Sep;24(20):3531-41. doi: 10.1016/s0142-9612(03)00222-9.</citation>
    <PMID>12809782</PMID>
  </reference>
  <reference>
    <citation>Sakai D, Mochida J, Iwashina T, Hiyama A, Omi H, Imai M, Nakai T, Ando K, Hotta T. Regenerative effects of transplanting mesenchymal stem cells embedded in atelocollagen to the degenerated intervertebral disc. Biomaterials. 2006 Jan;27(3):335-45. doi: 10.1016/j.biomaterials.2005.06.038. Epub 2005 Aug 19.</citation>
    <PMID>16112726</PMID>
  </reference>
  <reference>
    <citation>Sakai D, Mochida J, Iwashina T, Watanabe T, Nakai T, Ando K, Hotta T. Differentiation of mesenchymal stem cells transplanted to a rabbit degenerative disc model: potential and limitations for stem cell therapy in disc regeneration. Spine (Phila Pa 1976). 2005 Nov 1;30(21):2379-87. doi: 10.1097/01.brs.0000184365.28481.e3.</citation>
    <PMID>16261113</PMID>
  </reference>
  <reference>
    <citation>Crevensten G, Walsh AJ, Ananthakrishnan D, Page P, Wahba GM, Lotz JC, Berven S. Intervertebral disc cell therapy for regeneration: mesenchymal stem cell implantation in rat intervertebral discs. Ann Biomed Eng. 2004 Mar;32(3):430-4. doi: 10.1023/b:abme.0000017545.84833.7c.</citation>
    <PMID>15095817</PMID>
  </reference>
  <reference>
    <citation>Zhang YG, Guo X, Xu P, Kang LL, Li J. Bone mesenchymal stem cells transplanted into rabbit intervertebral discs can increase proteoglycans. Clin Orthop Relat Res. 2005 Jan;(430):219-26. doi: 10.1097/01.blo.0000146534.31120.cf.</citation>
    <PMID>15662327</PMID>
  </reference>
  <reference>
    <citation>Ho G, Leung VY, Cheung KM, Chan D. Effect of severity of intervertebral disc injury on mesenchymal stem cell-based regeneration. Connect Tissue Res. 2008;49(1):15-21. doi: 10.1080/03008200701818595.</citation>
    <PMID>18293174</PMID>
  </reference>
  <reference>
    <citation>Yi Z, Guanjun T, Lin C, Zifeng P. Effects of Transplantation of hTIMP-1-Expressing Bone Marrow Mesenchymal Stem Cells on the Extracellular Matrix of Degenerative Intervertebral Discs in an In Vivo Rabbit Model. Spine (Phila Pa 1976). 2014 May 15;39(11):E669-E675. doi: 10.1097/BRS.0000000000000316.</citation>
    <PMID>24718065</PMID>
  </reference>
  <reference>
    <citation>Wei A, Tao H, Chung SA, Brisby H, Ma DD, Diwan AD. The fate of transplanted xenogeneic bone marrow-derived stem cells in rat intervertebral discs. J Orthop Res. 2009 Mar;27(3):374-9. doi: 10.1002/jor.20567.</citation>
    <PMID>18853431</PMID>
  </reference>
  <reference>
    <citation>Jeong JH, Jin ES, Min JK, Jeon SR, Park CS, Kim HS, Choi KH. Human mesenchymal stem cells implantation into the degenerated coccygeal disc of the rat. Cytotechnology. 2009 Jan;59(1):55-64. doi: 10.1007/s10616-009-9192-1. Epub 2009 Apr 12.</citation>
    <PMID>19363673</PMID>
  </reference>
  <reference>
    <citation>Hiyama A, Mochida J, Iwashina T, Omi H, Watanabe T, Serigano K, Tamura F, Sakai D. Transplantation of mesenchymal stem cells in a canine disc degeneration model. J Orthop Res. 2008 May;26(5):589-600. doi: 10.1002/jor.20584.</citation>
    <PMID>18203202</PMID>
  </reference>
  <reference>
    <citation>Henriksson HB, Svanvik T, Jonsson M, Hagman M, Horn M, Lindahl A, Brisby H. Transplantation of human mesenchymal stems cells into intervertebral discs in a xenogeneic porcine model. Spine (Phila Pa 1976). 2009 Jan 15;34(2):141-8. doi: 10.1097/BRS.0b013e31818f8c20.</citation>
    <PMID>19112334</PMID>
  </reference>
  <reference>
    <citation>Zhang Y, Drapeau S, Howard SA, Thonar EJ, Anderson DG. Transplantation of goat bone marrow stromal cells to the degenerating intervertebral disc in a goat disc injury model. Spine (Phila Pa 1976). 2011 Mar 1;36(5):372-7. doi: 10.1097/BRS.0b013e3181d10401.</citation>
    <PMID>20890267</PMID>
  </reference>
  <reference>
    <citation>Jeong JH, Lee JH, Jin ES, Min JK, Jeon SR, Choi KH. Regeneration of intervertebral discs in a rat disc degeneration model by implanted adipose-tissue-derived stromal cells. Acta Neurochir (Wien). 2010 Oct;152(10):1771-7. doi: 10.1007/s00701-010-0698-2. Epub 2010 Jun 24.</citation>
    <PMID>20571835</PMID>
  </reference>
  <reference>
    <citation>Chun HJ, Kim YS, Kim BK, Kim EH, Kim JH, Do BR, Hwang SJ, Hwang JY, Lee YK. Transplantation of human adipose-derived stem cells in a rabbit model of traumatic degeneration of lumbar discs. World Neurosurg. 2012 Sep-Oct;78(3-4):364-71. doi: 10.1016/j.wneu.2011.12.084. Epub 2011 Dec 24.</citation>
    <PMID>22381275</PMID>
  </reference>
  <reference>
    <citation>Ganey T, Hutton WC, Moseley T, Hedrick M, Meisel HJ. Intervertebral disc repair using adipose tissue-derived stem and regenerative cells: experiments in a canine model. Spine (Phila Pa 1976). 2009 Oct 1;34(21):2297-304. doi: 10.1097/BRS.0b013e3181a54157.</citation>
    <PMID>19934809</PMID>
  </reference>
  <reference>
    <citation>Miyamoto T, Muneta T, Tabuchi T, Matsumoto K, Saito H, Tsuji K, Sekiya I. Intradiscal transplantation of synovial mesenchymal stem cells prevents intervertebral disc degeneration through suppression of matrix metalloproteinase-related genes in nucleus pulposus cells in rabbits. Arthritis Res Ther. 2010;12(6):R206. doi: 10.1186/ar3182. Epub 2010 Nov 5.</citation>
    <PMID>21054867</PMID>
  </reference>
  <reference>
    <citation>Leckie SK, Sowa GA, Bechara BP, Hartman RA, Coelho JP, Witt WT, Dong QD, Bowman BW, Bell KM, Vo NV, Kramer BC, Kang JD. Injection of human umbilical tissue-derived cells into the nucleus pulposus alters the course of intervertebral disc degeneration in vivo. Spine J. 2013 Mar;13(3):263-72. doi: 10.1016/j.spinee.2012.12.004. Epub 2013 Feb 4.</citation>
    <PMID>23384411</PMID>
  </reference>
  <reference>
    <citation>Pettine KA, Murphy MB, Suzuki RK, Sand TT. Percutaneous injection of autologous bone marrow concentrate cells significantly reduces lumbar discogenic pain through 12 months. Stem Cells. 2015 Jan;33(1):146-56. doi: 10.1002/stem.1845.</citation>
    <PMID>25187512</PMID>
  </reference>
  <reference>
    <citation>Vadala G, Sowa G, Hubert M, Gilbertson LG, Denaro V, Kang JD. Mesenchymal stem cells injection in degenerated intervertebral disc: cell leakage may induce osteophyte formation. J Tissue Eng Regen Med. 2012 May;6(5):348-55. doi: 10.1002/term.433. Epub 2011 Jun 13.</citation>
    <PMID>21671407</PMID>
  </reference>
  <reference>
    <citation>Hernigou P, Homma Y, Flouzat-Lachaniette CH, Poignard A, Chevallier N, Rouard H. Cancer risk is not increased in patients treated for orthopaedic diseases with autologous bone marrow cell concentrate. J Bone Joint Surg Am. 2013 Dec 18;95(24):2215-21. doi: 10.2106/JBJS.M.00261.</citation>
    <PMID>24352775</PMID>
  </reference>
  <verification_date>May 2020</verification_date>
  <study_first_submitted>May 6, 2020</study_first_submitted>
  <study_first_submitted_qc>May 31, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 4, 2020</study_first_posted>
  <last_update_submitted>May 31, 2020</last_update_submitted>
  <last_update_submitted_qc>May 31, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">June 4, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine</investigator_affiliation>
    <investigator_full_name>Qiang Fu</investigator_full_name>
    <investigator_title>Dean of the Minimally Invisive Spine Surgery Department</investigator_title>
  </responsible_party>
  <keyword>Lumbar Disc Degeneration</keyword>
  <keyword>Human Umbilical Cord Mesenchymal Stem Cells</keyword>
  <keyword>Lumbar Disc Herniation</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Intervertebral Disc Displacement</mesh_term>
    <mesh_term>Intervertebral Disc Degeneration</mesh_term>
    <mesh_term>Hernia</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>All the relative individual participant data (IPD) collected during the trial after deidentification</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
    <ipd_info_type>Analytic Code</ipd_info_type>
    <ipd_time_frame>Immediately following publication. No end date.</ipd_time_frame>
    <ipd_access_criteria>The researchers associate with disc degeneration and stem cells.</ipd_access_criteria>
  </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/NCT04414592
org study id: QFu
nct id: NCT04414592
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
This study aims to investigate the safety and efficiency of Human Umbilical Cord Mesenchymal
      Stem Cells (hUCMSC) for treating lumbar disc degeneration diseases. We hypothesize grafting
      hUCMSC into the degenerative disc leads to symptoms relief and slow down the progression of
      disc degeneration.
Lumbar disc herniation causes patients severe lower back pain and radicular pain to decrease
      the quality of life and lead to great economic burden to patients and society. In recent
      years, full endoscopic discectomy has been widely used in the treatment of lumbar disc
      herniation due to its advantages of reduced trauma, enhanced recovery and less cost. However,
      the reherniation of the residual nucleus pulposus still exist after nerve root decompression.
      It is urgent to use stem cell and tissue engineering to replace the resection tissue and
      repair the residual nucleus pulposus for disc resealing. To observe the safety and efficacy
      of human umbilical cord mesenchymal stem cells (hUCMSCs) in the treatment of lumbar disc
      degeneration. This clinical trial is aimed to include a single group of 20 patients with
      lumbar disc herniation. Twenty million hUCMSCs will be injected into the lumbar disc of the
      enrolled patients in this non-random, self-controlled and single-dose open study design. The
      patients will be followed up for 3 months, 6 months and 12 months after the injection to
      evaluate the safety of the patients after grafting hUCMSCs. Additionally, improvement of
      patients' quality of life will be evaluated using the ODI score, VAS score and SF-36 score.
      Lumbar disc signals will be also quantified using MRI to demonstrate hUCMSCs transplantation
      could slow down lumbar disc degeneration.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Lumbar disc signaling values from magnetic resonance imaging
time frame: Baseline, post-op 3months, post-op 6months, post-op 12months
description: Changes from baseline in Lumbar disc signaling values from magnetic resonance imaging
measure: Visual Analogue Scale (VAS) (0-10 scores, the higher scores mean a worse outcome)
time frame: Baseline, post-op 3months, post-op 6months, post-op 12months
description: Changes from baseline in Visual Analogue Scale of Lower back pain and leg pain
measure: Oswestry Disability Index(ODI) (0-50 scores, the higher scores mean a worse outcome)
time frame: Baseline, post-op 3months, post-op 6months, post-op 12months
description: Changes from baseline in Oswestry Disability Index
measure: The Short Form (36) Health survey (SF36) (0-100 scores, the higher scores mean a better outcome)
time frame: Baseline, post-op 3months, post-op 6months, post-op 12months
description: Changes from baseline in The Short Form (36) Health survey (SF36)
measure: Disc Height Index (DHI) from X ray
time frame: Baseline, post-op 3months, post-op 6months, post-op 12months
description: Changes from baseline in Disc Height Index
measure: Size of herniated nucleus pulposus from magnetic resonance imaging
time frame: Baseline, post-op 3months, post-op 6months, post-op 12months
description: Changes from baseline in size of nucleus pulposus from magnetic resonance imaging
measure: Number of participants with treatment-related adverse events by CTCAE v4.0
time frame: From baseline until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 12 months
description: Assessing for worsening of patients' baseline symptoms or functions (will be considered an AE); (also general AE events), particular AE events related to the procedures/treatment. All AEs will be assessed by common terminology criteria for adverse events.
arm group label: Human Umbilical Cord Mesenchymal Stem Cells
arm group type: Experimental
description: Injection of twenty million human umbilical cord mesenchymal stem cells into the degenerative disc
intervention type: Other
intervention name: human umbilical cord mesenchymal stem cells
description: Twenty million human umbilical cord mesenchymal stem cells will be immediately injected into the degenerative discs of such patients who are diagnosed with lumbar disc herniation and operated with full endoscopy lumbar discectomy.
arm group label: Human Umbilical Cord Mesenchymal Stem Cells
criteria: 
gender: All
minimum age: 18 Years
maximum age: 60 Years
healthy volunteers: No
last name: Qiang Fu, M.D.
role: Principal Investigator
affiliation: Minimally Invasive Spinal of Shanghai General Hospital
last name: Song Guo, M.D.
phone: 15901836457
email: guosongtj@163.com
last name: Jigang Zhang, M.D.
phone: 18621155781
email: 2293259778@qq.com
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
country: China
citation: Walker BF. The prevalence of low back pain: a systematic review of the literature from 1966 to 1998. J Spinal Disord. 2000 Jun;13(3):205-17. doi: 10.1097/00002517-200006000-00003.
PMID: 10872758
citation: Ghiselli G, Wang JC, Bhatia NN, Hsu WK, Dawson EG. Adjacent segment degeneration in the lumbar spine. J Bone Joint Surg Am. 2004 Jul;86(7):1497-503. doi: 10.2106/00004623-200407000-00020.
PMID: 15252099
citation: Chen Z, Zhang L, Dong J, Xie P, Liu B, Wang Q, Chen R, Shu T, Li S, Feng F, Yang B, He L, Yang Y, Liu Z, Pang M, Rong L. Percutaneous Transforaminal Endoscopic Discectomy Versus Microendoscopic Discectomy for Lumbar Disc Herniation: Two-Year Results of a Randomized Controlled Trial. Spine (Phila Pa 1976). 2020 Apr 15;45(8):493-503. doi: 10.1097/BRS.0000000000003314.
PMID: 31703056
citation: Li Z, Lang G, Chen X, Sacks H, Mantzur C, Tropp U, Mader KT, Smallwood TC, Sammon C, Richards RG, Alini M, Grad S. Polyurethane scaffold with in situ swelling capacity for nucleus pulposus replacement. Biomaterials. 2016 Apr;84:196-209. doi: 10.1016/j.biomaterials.2016.01.040. Epub 2016 Jan 21.
PMID: 26828684
citation: Moriguchi Y, Mojica-Santiago J, Grunert P, Pennicooke B, Berlin C, Khair T, Navarro-Ramirez R, Ricart Arbona RJ, Nguyen J, Hartl R, Bonassar LJ. Total disc replacement using tissue-engineered intervertebral discs in the canine cervical spine. PLoS One. 2017 Oct 20;12(10):e0185716. doi: 10.1371/journal.pone.0185716. eCollection 2017.
PMID: 29053719
citation: Benneker LM, Andersson G, Iatridis JC, Sakai D, Hartl R, Ito K, Grad S. Cell therapy for intervertebral disc repair: advancing cell therapy from bench to clinics. Eur Cell Mater. 2014 May 6;27:5-11. doi: 10.22203/ecm.v027sa02.
PMID: 24802611
citation: Sobajima S, Vadala G, Shimer A, Kim JS, Gilbertson LG, Kang JD. Feasibility of a stem cell therapy for intervertebral disc degeneration. Spine J. 2008 Nov-Dec;8(6):888-96. doi: 10.1016/j.spinee.2007.09.011. Epub 2007 Dec 21.
PMID: 18082460
citation: Sakai D, Mochida J, Yamamoto Y, Nomura T, Okuma M, Nishimura K, Nakai T, Ando K, Hotta T. Transplantation of mesenchymal stem cells embedded in Atelocollagen gel to the intervertebral disc: a potential therapeutic model for disc degeneration. Biomaterials. 2003 Sep;24(20):3531-41. doi: 10.1016/s0142-9612(03)00222-9.
PMID: 12809782
citation: Sakai D, Mochida J, Iwashina T, Hiyama A, Omi H, Imai M, Nakai T, Ando K, Hotta T. Regenerative effects of transplanting mesenchymal stem cells embedded in atelocollagen to the degenerated intervertebral disc. Biomaterials. 2006 Jan;27(3):335-45. doi: 10.1016/j.biomaterials.2005.06.038. Epub 2005 Aug 19.
PMID: 16112726
citation: Sakai D, Mochida J, Iwashina T, Watanabe T, Nakai T, Ando K, Hotta T. Differentiation of mesenchymal stem cells transplanted to a rabbit degenerative disc model: potential and limitations for stem cell therapy in disc regeneration. Spine (Phila Pa 1976). 2005 Nov 1;30(21):2379-87. doi: 10.1097/01.brs.0000184365.28481.e3.
PMID: 16261113
citation: Crevensten G, Walsh AJ, Ananthakrishnan D, Page P, Wahba GM, Lotz JC, Berven S. Intervertebral disc cell therapy for regeneration: mesenchymal stem cell implantation in rat intervertebral discs. Ann Biomed Eng. 2004 Mar;32(3):430-4. doi: 10.1023/b:abme.0000017545.84833.7c.
PMID: 15095817
citation: Zhang YG, Guo X, Xu P, Kang LL, Li J. Bone mesenchymal stem cells transplanted into rabbit intervertebral discs can increase proteoglycans. Clin Orthop Relat Res. 2005 Jan;(430):219-26. doi: 10.1097/01.blo.0000146534.31120.cf.
PMID: 15662327
citation: Ho G, Leung VY, Cheung KM, Chan D. Effect of severity of intervertebral disc injury on mesenchymal stem cell-based regeneration. Connect Tissue Res. 2008;49(1):15-21. doi: 10.1080/03008200701818595.
PMID: 18293174
citation: Yi Z, Guanjun T, Lin C, Zifeng P. Effects of Transplantation of hTIMP-1-Expressing Bone Marrow Mesenchymal Stem Cells on the Extracellular Matrix of Degenerative Intervertebral Discs in an In Vivo Rabbit Model. Spine (Phila Pa 1976). 2014 May 15;39(11):E669-E675. doi: 10.1097/BRS.0000000000000316.
PMID: 24718065
citation: Wei A, Tao H, Chung SA, Brisby H, Ma DD, Diwan AD. The fate of transplanted xenogeneic bone marrow-derived stem cells in rat intervertebral discs. J Orthop Res. 2009 Mar;27(3):374-9. doi: 10.1002/jor.20567.
PMID: 18853431
citation: Jeong JH, Jin ES, Min JK, Jeon SR, Park CS, Kim HS, Choi KH. Human mesenchymal stem cells implantation into the degenerated coccygeal disc of the rat. Cytotechnology. 2009 Jan;59(1):55-64. doi: 10.1007/s10616-009-9192-1. Epub 2009 Apr 12.
PMID: 19363673
citation: Hiyama A, Mochida J, Iwashina T, Omi H, Watanabe T, Serigano K, Tamura F, Sakai D. Transplantation of mesenchymal stem cells in a canine disc degeneration model. J Orthop Res. 2008 May;26(5):589-600. doi: 10.1002/jor.20584.
PMID: 18203202
citation: Henriksson HB, Svanvik T, Jonsson M, Hagman M, Horn M, Lindahl A, Brisby H. Transplantation of human mesenchymal stems cells into intervertebral discs in a xenogeneic porcine model. Spine (Phila Pa 1976). 2009 Jan 15;34(2):141-8. doi: 10.1097/BRS.0b013e31818f8c20.
PMID: 19112334
citation: Zhang Y, Drapeau S, Howard SA, Thonar EJ, Anderson DG. Transplantation of goat bone marrow stromal cells to the degenerating intervertebral disc in a goat disc injury model. Spine (Phila Pa 1976). 2011 Mar 1;36(5):372-7. doi: 10.1097/BRS.0b013e3181d10401.
PMID: 20890267
citation: Jeong JH, Lee JH, Jin ES, Min JK, Jeon SR, Choi KH. Regeneration of intervertebral discs in a rat disc degeneration model by implanted adipose-tissue-derived stromal cells. Acta Neurochir (Wien). 2010 Oct;152(10):1771-7. doi: 10.1007/s00701-010-0698-2. Epub 2010 Jun 24.
PMID: 20571835
citation: Chun HJ, Kim YS, Kim BK, Kim EH, Kim JH, Do BR, Hwang SJ, Hwang JY, Lee YK. Transplantation of human adipose-derived stem cells in a rabbit model of traumatic degeneration of lumbar discs. World Neurosurg. 2012 Sep-Oct;78(3-4):364-71. doi: 10.1016/j.wneu.2011.12.084. Epub 2011 Dec 24.
PMID: 22381275
citation: Ganey T, Hutton WC, Moseley T, Hedrick M, Meisel HJ. Intervertebral disc repair using adipose tissue-derived stem and regenerative cells: experiments in a canine model. Spine (Phila Pa 1976). 2009 Oct 1;34(21):2297-304. doi: 10.1097/BRS.0b013e3181a54157.
PMID: 19934809
citation: Miyamoto T, Muneta T, Tabuchi T, Matsumoto K, Saito H, Tsuji K, Sekiya I. Intradiscal transplantation of synovial mesenchymal stem cells prevents intervertebral disc degeneration through suppression of matrix metalloproteinase-related genes in nucleus pulposus cells in rabbits. Arthritis Res Ther. 2010;12(6):R206. doi: 10.1186/ar3182. Epub 2010 Nov 5.
PMID: 21054867
citation: Leckie SK, Sowa GA, Bechara BP, Hartman RA, Coelho JP, Witt WT, Dong QD, Bowman BW, Bell KM, Vo NV, Kramer BC, Kang JD. Injection of human umbilical tissue-derived cells into the nucleus pulposus alters the course of intervertebral disc degeneration in vivo. Spine J. 2013 Mar;13(3):263-72. doi: 10.1016/j.spinee.2012.12.004. Epub 2013 Feb 4.
PMID: 23384411
citation: Pettine KA, Murphy MB, Suzuki RK, Sand TT. Percutaneous injection of autologous bone marrow concentrate cells significantly reduces lumbar discogenic pain through 12 months. Stem Cells. 2015 Jan;33(1):146-56. doi: 10.1002/stem.1845.
PMID: 25187512
citation: Vadala G, Sowa G, Hubert M, Gilbertson LG, Denaro V, Kang JD. Mesenchymal stem cells injection in degenerated intervertebral disc: cell leakage may induce osteophyte formation. J Tissue Eng Regen Med. 2012 May;6(5):348-55. doi: 10.1002/term.433. Epub 2011 Jun 13.
PMID: 21671407
citation: Hernigou P, Homma Y, Flouzat-Lachaniette CH, Poignard A, Chevallier N, Rouard H. Cancer risk is not increased in patients treated for orthopaedic diseases with autologous bone marrow cell concentrate. J Bone Joint Surg Am. 2013 Dec 18;95(24):2215-21. doi: 10.2106/JBJS.M.00261.
PMID: 24352775
responsible party type: Principal Investigator
investigator affiliation: Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine
investigator full name: Qiang Fu
investigator title: Dean of the Minimally Invisive Spine Surgery Department
mesh term: Intervertebral Disc Displacement
mesh term: Intervertebral Disc Degeneration
mesh term: Hernia
sharing ipd: Yes
ipd description: All the relative individual participant data (IPD) collected during the trial after deidentification
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Informed Consent Form (ICF)
ipd info type: Clinical Study Report (CSR)
ipd info type: Analytic Code
ipd time frame: Immediately following publication. No end date.
ipd access criteria: The researchers associate with disc degeneration and stem cells.