<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/NCT02966717</url>
  </required_header>
  <id_info>
    <org_study_id>Tangxun8022</org_study_id>
    <nct_id>NCT02966717</nct_id>
  </id_info>
  <brief_title>Rituximab Combined With MSCs in the Treatment of PNS (3-4 Stage of CKD)</brief_title>
  <acronym>CKD</acronym>
  <official_title>The Clinical Study of Rituximab Combined With Mesenchymal Stem Cells in the Treatment of Primary Nephrotic Syndrome (3-4 Stage of Chronic Kidney Disease)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Zhujiang Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Zhujiang Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Primary nephrotic syndrome(PNS) is a group of clinical symptoms caused by a variety of&#xD;
      factors, including immune,environmental, genetic, et al. Oral corticosteroids have been to be&#xD;
      the preferred drug for the treatment of PNS, but the long-term use of glucocorticoid therapy&#xD;
      in clinic often induces some problems such as hormone dependent and hormone resistance, as&#xD;
      well as severe side effects which act as a threat to the patients' health. Besides, patients&#xD;
      with proteinuria long-term not control often behave faster progression into chronic renal&#xD;
      failure, leading to poor prognosis. In renal diseases, Rituximab ( RTX) is often used in the&#xD;
      treatment of refractory nephropathy, such as hormone dependent nephrotic syndrome, hormone&#xD;
      resistance nephrotic syndrome, frequency recurrence nephrotic syndrome, which shows exciting&#xD;
      effects in delaying the development of the disease.At present, mesenchymal stem cells ( MSCs)&#xD;
      has been used as a research hotspot to repair the tissue damage of chronic kidney disease,&#xD;
      and it also behaves certain effects. The purpose of this study is to seek a more targeted&#xD;
      treatment, more precise curative effect and more feasibility treatment for PNS(CKD3-4),so as&#xD;
      to delay or reverse the disease and improve the quality of life of patients with CKD.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Primary nephrotic syndrome(PNS) is a group of clinical symptoms caused by a variety of&#xD;
      factors, including immune,environmental, genetic, et al. Oral corticosteroids have been to be&#xD;
      the preferred drug for the treatment of PNS, but the long-term use of glucocorticoid therapy&#xD;
      in clinic often induces some problems such as hormone dependent and hormone resistance, as&#xD;
      well as severe side effects which act as a threat to the patients' health. On the treatment&#xD;
      of nephrotic syndrome in the latest evidence-based practice guidelines, Japan and Kidney&#xD;
      Disease: Improving Global Outcomes(KDIGO) still have no high-level-evidence recommendation&#xD;
      for the steroid resistant PNS and those patients with renal function significantly impaired.&#xD;
      In addition, a large number of patients with proteinuria long-term not control often behave&#xD;
      faster progression into chronic renal failure, leading to poor prognosis. What's more,&#xD;
      patients holding the progression into 3-4 stage of chronic kidney disease with nephrotic&#xD;
      syndrome ofen can not tolerate the conventional immunosuppressive therapy, thus cause faster&#xD;
      progression into end-stage renal disease. There is no better treatment method for this&#xD;
      phenomenon nowadays. Therefore, it is particularly important to explore new treatment options&#xD;
      for the clinical disease described above.&#xD;
&#xD;
      In renal diseases, Rituximab ( RTX) is often used in the treatment of refractory nephropathy,&#xD;
      such as hormone dependent nephrotic syndrome, hormone resistance nephrotic syndrome,&#xD;
      frequency recurrence nephrotic syndrome, which shows exciting effects in delaying the&#xD;
      development of the disease. An observational、 multicenter、 retrospective study about the&#xD;
      therapeutic effect of RTX on adult minimal change nephrotic syndrome (MCNS) was conducted.&#xD;
      This study confirmed that RTX is safe and effective in the treatment of adult patients with&#xD;
      MCNS, which can be used as an alternative treatment options for MCNS patients with long-term&#xD;
      recurrence. Whereas, whether the rituximab in the treatment of PNS (MCNS or other types of&#xD;
      NS) combined with CKD plays the same role on delaying the progression of renal disease, there&#xD;
      is no relevant clinical trials reported.&#xD;
&#xD;
      At present, mesenchymal stem cells ( MSCs) has been used as a research hotspot to repair the&#xD;
      tissue damage of chronic kidney disease, and it also behaves certain effects. Clinical&#xD;
      Studies about the treatment of PNS by the umbilical cord mesenchymal stem cells or the&#xD;
      treatment of CKD by the bone marrow mesenchymal stem cells suggest that the mesenchymal stem&#xD;
      cells can improve the patients's condition with PNS or CKD. However, cell therapy in the&#xD;
      clinical trials in patients with CKD is rarely to be seen, and there is no definitive&#xD;
      conclusion. Accordingly, more clinical studies are needed to assess the effectiveness,&#xD;
      feasibility and safety of cell therapy, as well as formulating standard treatment plans.&#xD;
&#xD;
      We have accumulated 3 cases of patients with chronic kidney disease(in the 3-4 stage),&#xD;
      accompanied with a large number of proteinuria and renal function declining rapidly,&#xD;
      providing RTX infusion combined with mesenchymal stem cell.&#xD;
&#xD;
      Of which, 3 patients had significantly reduced proteinuria, 2 cases showed different levels&#xD;
      improvement of renal function, 1 cases kept stable renal function. There was no obvious&#xD;
      adverse reaction and safety risk, but more clinical trials was still required. In addition,&#xD;
      our team has carried out a project about autologous non-clearing bone marrow stem cell&#xD;
      transplantation in the treatment of severe lupus associated with renal function impaired.&#xD;
      This study revealed good treatment effect, which can provide some certain clinical work&#xD;
      foundation and experience for our following research.&#xD;
&#xD;
      In summary, we intend to conduct a prospective、 single-center、 randomized 、controlled&#xD;
      clinical study, uniting the Third Affiliated Hospital of Southern Medical University together&#xD;
      to explore the effectiveness and safety of rituximab combined with mesenchymal stem cells for&#xD;
      the treatment of PNS(CKD3-4). The purpose of this study is to seek a more targeted treatment,&#xD;
      more precise curative effect and more feasibility treatment for PNS(CKD3-4),so as to delay or&#xD;
      reverse the disease and improve the quality of life of patients with CKD.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date>August 2016</start_date>
  <completion_date type="Anticipated">October 2021</completion_date>
  <primary_completion_date type="Actual">October 2016</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>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>The change of serum creatinine elevation</measure>
    <time_frame>4 weeks, 8 weeks, 12 weeks</time_frame>
    <description>The serum creatine elevation should be tested for at least 4 times, as follows, before treatment, 4 weeks after treatment, 8 weeks after treatment, 12 weeks after treatment.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>The percentage of end-stage renal disease or death.</measure>
    <time_frame>3 years</time_frame>
    <description>The percentage of end-stage renal disease or death should be less than 60%.</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">116</enrollment>
  <condition>Renal Insufficiency, Chronic</condition>
  <condition>Nephrotic Syndrome</condition>
  <arm_group>
    <arm_group_label>parallel control of conventional therapy</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Intervention of conventional therapy group: controlling blood pressure using amlodipine, valsartan, metoprolol and terazosin and so on , protecting the renal function using bailing capsule, alpha keto acid, low molecular weight heparin and so on.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>experimental group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Intervention of Rituximab combined with mesenchymal stem cells group: as follows, Rituximab, 100mg/time every one week, the infusion should be a total of 4 times; and then after at least 4 days interval after the first and the third infusion of the Rituximab , the dosage of mesenchymal stem cells tends to be 10^6/kg/time every 2 weeks, while the infusion should be a total of 2 times.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Rituximab</intervention_name>
    <description>Rituximab is a human-mouse-chimeric monoclonal antibody which was approved in 1997 for the treatment of cancer.</description>
    <arm_group_label>experimental group</arm_group_label>
    <other_name>Mabthera</other_name>
    <other_name>RTX</other_name>
    <other_name>Rituxan</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>conventional therapy</intervention_name>
    <description>Intervention of conventional therapy group: controlling blood pressure using amlodipine, valsartan, metoprolol and terazosin and so on , protecting the renal function using bailing capsule, alpha keto acid, low molecular weight heparin and so on.</description>
    <arm_group_label>parallel control of conventional therapy</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Mesenchymal stem cells</intervention_name>
    <description>Mesenchymal stem cells (MSCs), which belongs to mesoderm, is a kind of somatic stem cell with the ability of self-replication and the potential of multi-directional differentiation.</description>
    <arm_group_label>experimental group</arm_group_label>
    <other_name>MSCs</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Gender-Definition: Physical gender of individuals who may participate in the protocol.&#xD;
        Select one-Both: both female and male participants are being studied.&#xD;
&#xD;
        Age Limits-Minimum Age( Definition: Minimum age of participants. ); Maximum Age&#xD;
        (Definition: Maximum age of participants).&#xD;
&#xD;
        Accepts Healthy Volunteers?-Definition: Indicate if persons who have not had the&#xD;
        condition(s) being studied or otherwise related conditions or symptoms, as specified in the&#xD;
        eligibility requirements, may participate in the study.&#xD;
&#xD;
        Eligibility Criteria-Definition: Summary criteria for participant selection. The preferred&#xD;
        format includes lists of inclusion and exclusion criteria as shown below.&#xD;
&#xD;
        Inclusion Criteria: A. Nephrotic syndrome(urine protein &gt; 3.5g/d and serum albumin &lt;&#xD;
        30g/L）； B. 3-4 stage of CKD [glomerular filtration rate 15-59 ml/ (min ·1.73m²)]； C. Age&#xD;
        should be 18-65 years old； D. Accept treatment and signe informed consent voluntarily.&#xD;
&#xD;
        - Exclusion Criteria:A. Secondary nephrotic syndrome such as systemic lupus erythematosis&#xD;
        nephritis, anaphylactic purpura nephritis and diabetic nephropathy and so on； B.&#xD;
        Complications like severe infection, cardiovascular diseases, severe heart and lung as well&#xD;
        as liver complications； C. Dialysis is extremely urgent； D. Obstructive urinary tract&#xD;
        diseases； E. Creatinine rises more than 30% of the based value in nearly 3 months； F.&#xD;
        Pregnancy or in lactation； G. Any other conditions that researchers consider not suitable&#xD;
        to participate in this trial.&#xD;
&#xD;
        -&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Tang Xun, doctor</last_name>
    <role>Principal Investigator</role>
    <affiliation>Zhujiang Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Zhujiang Hospital, Southern Medical University</name>
      <address>
        <city>Guangzhou</city>
        <state>Guangdong</state>
        <zip>510282</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>November 2016</verification_date>
  <study_first_submitted>October 30, 2016</study_first_submitted>
  <study_first_submitted_qc>November 14, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 17, 2016</study_first_posted>
  <last_update_submitted>November 18, 2016</last_update_submitted>
  <last_update_submitted_qc>November 18, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">November 22, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Rituximab</keyword>
  <keyword>Mesenchymal stem cells</keyword>
  <keyword>primary nephrotic syndrome</keyword>
  <keyword>chronic kidney disease</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Renal Insufficiency</mesh_term>
    <mesh_term>Nephrotic Syndrome</mesh_term>
    <mesh_term>Nephrosis</mesh_term>
    <mesh_term>Renal Insufficiency, Chronic</mesh_term>
    <mesh_term>Syndrome</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Rituximab</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT02966717
org study id: Tangxun8022
nct id: NCT02966717
lead sponsor: 
has dmc: Yes
Primary nephrotic syndrome(PNS) is a group of clinical symptoms caused by a variety of
      factors, including immune,environmental, genetic, et al. Oral corticosteroids have been to be
      the preferred drug for the treatment of PNS, but the long-term use of glucocorticoid therapy
      in clinic often induces some problems such as hormone dependent and hormone resistance, as
      well as severe side effects which act as a threat to the patients' health. Besides, patients
      with proteinuria long-term not control often behave faster progression into chronic renal
      failure, leading to poor prognosis. In renal diseases, Rituximab ( RTX) is often used in the
      treatment of refractory nephropathy, such as hormone dependent nephrotic syndrome, hormone
      resistance nephrotic syndrome, frequency recurrence nephrotic syndrome, which shows exciting
      effects in delaying the development of the disease.At present, mesenchymal stem cells ( MSCs)
      has been used as a research hotspot to repair the tissue damage of chronic kidney disease,
      and it also behaves certain effects. The purpose of this study is to seek a more targeted
      treatment, more precise curative effect and more feasibility treatment for PNS(CKD3-4),so as
      to delay or reverse the disease and improve the quality of life of patients with CKD.
Primary nephrotic syndrome(PNS) is a group of clinical symptoms caused by a variety of
      factors, including immune,environmental, genetic, et al. Oral corticosteroids have been to be
      the preferred drug for the treatment of PNS, but the long-term use of glucocorticoid therapy
      in clinic often induces some problems such as hormone dependent and hormone resistance, as
      well as severe side effects which act as a threat to the patients' health. On the treatment
      of nephrotic syndrome in the latest evidence-based practice guidelines, Japan and Kidney
      Disease: Improving Global Outcomes(KDIGO) still have no high-level-evidence recommendation
      for the steroid resistant PNS and those patients with renal function significantly impaired.
      In addition, a large number of patients with proteinuria long-term not control often behave
      faster progression into chronic renal failure, leading to poor prognosis. What's more,
      patients holding the progression into 3-4 stage of chronic kidney disease with nephrotic
      syndrome ofen can not tolerate the conventional immunosuppressive therapy, thus cause faster
      progression into end-stage renal disease. There is no better treatment method for this
      phenomenon nowadays. Therefore, it is particularly important to explore new treatment options
      for the clinical disease described above.

      In renal diseases, Rituximab ( RTX) is often used in the treatment of refractory nephropathy,
      such as hormone dependent nephrotic syndrome, hormone resistance nephrotic syndrome,
      frequency recurrence nephrotic syndrome, which shows exciting effects in delaying the
      development of the disease. An observational、 multicenter、 retrospective study about the
      therapeutic effect of RTX on adult minimal change nephrotic syndrome (MCNS) was conducted.
      This study confirmed that RTX is safe and effective in the treatment of adult patients with
      MCNS, which can be used as an alternative treatment options for MCNS patients with long-term
      recurrence. Whereas, whether the rituximab in the treatment of PNS (MCNS or other types of
      NS) combined with CKD plays the same role on delaying the progression of renal disease, there
      is no relevant clinical trials reported.

      At present, mesenchymal stem cells ( MSCs) has been used as a research hotspot to repair the
      tissue damage of chronic kidney disease, and it also behaves certain effects. Clinical
      Studies about the treatment of PNS by the umbilical cord mesenchymal stem cells or the
      treatment of CKD by the bone marrow mesenchymal stem cells suggest that the mesenchymal stem
      cells can improve the patients's condition with PNS or CKD. However, cell therapy in the
      clinical trials in patients with CKD is rarely to be seen, and there is no definitive
      conclusion. Accordingly, more clinical studies are needed to assess the effectiveness,
      feasibility and safety of cell therapy, as well as formulating standard treatment plans.

      We have accumulated 3 cases of patients with chronic kidney disease(in the 3-4 stage),
      accompanied with a large number of proteinuria and renal function declining rapidly,
      providing RTX infusion combined with mesenchymal stem cell.

      Of which, 3 patients had significantly reduced proteinuria, 2 cases showed different levels
      improvement of renal function, 1 cases kept stable renal function. There was no obvious
      adverse reaction and safety risk, but more clinical trials was still required. In addition,
      our team has carried out a project about autologous non-clearing bone marrow stem cell
      transplantation in the treatment of severe lupus associated with renal function impaired.
      This study revealed good treatment effect, which can provide some certain clinical work
      foundation and experience for our following research.

      In summary, we intend to conduct a prospective、 single-center、 randomized 、controlled
      clinical study, uniting the Third Affiliated Hospital of Southern Medical University together
      to explore the effectiveness and safety of rituximab combined with mesenchymal stem cells for
      the treatment of PNS(CKD3-4). The purpose of this study is to seek a more targeted treatment,
      more precise curative effect and more feasibility treatment for PNS(CKD3-4),so as to delay or
      reverse the disease and improve the quality of life of patients with CKD.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: The change of serum creatinine elevation
time frame: 4 weeks, 8 weeks, 12 weeks
description: The serum creatine elevation should be tested for at least 4 times, as follows, before treatment, 4 weeks after treatment, 8 weeks after treatment, 12 weeks after treatment.
measure: The percentage of end-stage renal disease or death.
time frame: 3 years
description: The percentage of end-stage renal disease or death should be less than 60%.
arm group label: parallel control of conventional therapy
arm group type: Active Comparator
description: Intervention of conventional therapy group: controlling blood pressure using amlodipine, valsartan, metoprolol and terazosin and so on , protecting the renal function using bailing capsule, alpha keto acid, low molecular weight heparin and so on.
arm group label: experimental group
arm group type: Experimental
description: Intervention of Rituximab combined with mesenchymal stem cells group: as follows, Rituximab, 100mg/time every one week, the infusion should be a total of 4 times; and then after at least 4 days interval after the first and the third infusion of the Rituximab , the dosage of mesenchymal stem cells tends to be 10^6/kg/time every 2 weeks, while the infusion should be a total of 2 times.
intervention type: Drug
intervention name: Rituximab
description: Rituximab is a human-mouse-chimeric monoclonal antibody which was approved in 1997 for the treatment of cancer.
arm group label: experimental group
other name: Mabthera
other name: RTX
other name: Rituxan
intervention type: Drug
intervention name: conventional therapy
description: Intervention of conventional therapy group: controlling blood pressure using amlodipine, valsartan, metoprolol and terazosin and so on , protecting the renal function using bailing capsule, alpha keto acid, low molecular weight heparin and so on.
arm group label: parallel control of conventional therapy
intervention type: Drug
intervention name: Mesenchymal stem cells
description: Mesenchymal stem cells (MSCs), which belongs to mesoderm, is a kind of somatic stem cell with the ability of self-replication and the potential of multi-directional differentiation.
arm group label: experimental group
other name: MSCs
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Tang Xun, doctor
role: Principal Investigator
affiliation: Zhujiang Hospital
facility: 
country: China
responsible party type: Sponsor
mesh term: Renal Insufficiency
mesh term: Nephrotic Syndrome
mesh term: Nephrosis
mesh term: Renal Insufficiency, Chronic
mesh term: Syndrome
mesh term: Rituximab
sharing ipd: Undecided