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Rituximab Combined With MSCs in the Treatment of PNS (3-4 Stage of CKD) (CKD)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02966717
Recruitment Status : Active, not recruiting
First Posted : November 17, 2016
Last Update Posted : November 22, 2016
Sponsor:
Information provided by (Responsible Party):
Zhujiang Hospital

Tracking Information
First Submitted Date  ICMJE October 30, 2016
First Posted Date  ICMJE November 17, 2016
Last Update Posted Date November 22, 2016
Study Start Date  ICMJE August 2016
Actual Primary Completion Date October 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 18, 2016)
  • The change of serum creatinine elevation [ Time Frame: 4 weeks, 8 weeks, 12 weeks ]
    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.
  • The percentage of end-stage renal disease or death. [ Time Frame: 3 years ]
    The percentage of end-stage renal disease or death should be less than 60%.
Original Primary Outcome Measures  ICMJE
 (submitted: November 14, 2016)
  • The change of serum creatinine elevation [ Time Frame: 12 weeks ]
    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.
  • The percentage of end-stage renal disease or death. [ Time Frame: 3 years ]
    The percentage of end-stage renal disease or death should be less than 60%.
Change History Complete list of historical versions of study NCT02966717 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Rituximab Combined With MSCs in the Treatment of PNS (3-4 Stage of CKD)
Official Title  ICMJE The Clinical Study of Rituximab Combined With Mesenchymal Stem Cells in the Treatment of Primary Nephrotic Syndrome (3-4 Stage of Chronic Kidney Disease)
Brief Summary 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.
Detailed Description

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Renal Insufficiency, Chronic
  • Nephrotic Syndrome
Intervention  ICMJE
  • Drug: Rituximab
    Rituximab is a human-mouse-chimeric monoclonal antibody which was approved in 1997 for the treatment of cancer.
    Other Names:
    • Mabthera
    • RTX
    • Rituxan
  • Drug: conventional therapy
    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.
  • Drug: Mesenchymal stem cells
    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.
    Other Name: MSCs
Study Arms  ICMJE
  • Active Comparator: parallel control of conventional therapy
    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.
    Intervention: Drug: conventional therapy
  • Experimental: experimental group
    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.
    Interventions:
    • Drug: Rituximab
    • Drug: Mesenchymal stem cells
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: November 14, 2016)
116
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE October 2021
Actual Primary Completion Date October 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Gender-Definition: Physical gender of individuals who may participate in the protocol. Select one-Both: both female and male participants are being studied.

Age Limits-Minimum Age( Definition: Minimum age of participants. ); Maximum Age (Definition: Maximum age of participants).

Accepts Healthy Volunteers?-Definition: Indicate if persons who have not had the condition(s) being studied or otherwise related conditions or symptoms, as specified in the eligibility requirements, may participate in the study.

Eligibility Criteria-Definition: Summary criteria for participant selection. The preferred format includes lists of inclusion and exclusion criteria as shown below.

Inclusion Criteria: A. Nephrotic syndrome(urine protein > 3.5g/d and serum albumin < 30g/L); B. 3-4 stage of CKD [glomerular filtration rate 15-59 ml/ (min ·1.73m²)]; C. Age should be 18-65 years old; D. Accept treatment and signe informed consent voluntarily.

- Exclusion Criteria:A. Secondary nephrotic syndrome such as systemic lupus erythematosis nephritis, anaphylactic purpura nephritis and diabetic nephropathy and so on; B. Complications like severe infection, cardiovascular diseases, severe heart and lung as well as liver complications; C. Dialysis is extremely urgent; D. Obstructive urinary tract diseases; E. Creatinine rises more than 30% of the based value in nearly 3 months; F. Pregnancy or in lactation; G. Any other conditions that researchers consider not suitable to participate in this trial.

-

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE China
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02966717
Other Study ID Numbers  ICMJE Tangxun8022
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Zhujiang Hospital
Study Sponsor  ICMJE Zhujiang Hospital
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Tang Xun, doctor Zhujiang Hospital
PRS Account Zhujiang Hospital
Verification Date November 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP