Human Umbilical Cord Mesenchymal Stem Cells Treatment for Lupus Nephritis (LN)
|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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT03580291|
Recruitment Status : Not yet recruiting
First Posted : July 9, 2018
Last Update Posted : July 10, 2018
|Condition or disease||Intervention/treatment||Phase|
|Lupus Nephritis||Other: Mesenchymal stem cells Drug: Mycophenolate Mofetil Other: Placebo of Mesenchymal stem cells Drug: Placebo of Mycophenolate Mofetil||Phase 2|
Lupus nephritis (LN) is one of the most serious complications and the main cause of death in patients with systemic lupus erythematosus (SLE). Type III, type IV and type V LN are severe clinical entities with poor prognosis, and its treatment remains challenging. Currently, type III, type IV, type V, type III plus V and type IV plus V LN are treated mainly according to the guidelines developed by KDIGO and the European Association for Anti-Rheumatism and European League Against Rheumatism/European Renal Association-European Dialysis and Transplant Association (EULAR/ERAEDTA). The main therapeutic regimens recommended by these guidelines include glucocorticoid combined with immunosuppressants such as cyclophosphamide (CTX), mycophenolate mofetil (MMF), etc. These medications can significantly induce disease remission and improve the long-term survival. However, some patients do not adequately response to the treatment of the combination of steroids and immunosuppressants, and the disease activity cannot be well-controlled. The high prevalence of steroids and immunosuppressants related adverse effects, such as steroid-related diabetes, bone necrosis, hypertension, peptic ulcer, CTX-related bone marrow and gonadal suppression, MMF-related infection risk and so on, have been found in long-term follow-up study. In addition, to date, there is insufficient data to support the use of new biologics, such as rituximab and abatacept in the induction therapy in patients with LN.
Mesenchymal stem cells (MSCs) can be obtained from several tissues and possess multiple differentiation potencies and immunomodulatory effects. The investigators have investigated the usefulness, and confirmed the efficacy and safety of MSC treatment of LN in animal models, in vitro experiments and phase I clinical trial. The studies also for the first time found that the MSC abnormalities are involved in the onset and development of lupus both in the lupus mice model and in SLE patients. The investigators found that the efficacy of allogeneic (xenogeneic) MSC transplantation is superior to autologous MSC transplantation in LN mice model. Thus, in current opinion, SLE is not only a hematopoietic stem cell disease, but also a mesenchymal stem cell disease. The investigators treated the refractory LN patients with allogenic MSC treatment, the outcomes revealed that the total response rate was 60%, the mortality rate of 2 to 5 years decreased from 35% - 45% to 6%. These results strongly support the use of allogenic MSC transplantation in the refractory LN patients. The mechanisms of MSC treatment include correcting the immune unbalance, inducing immune tolerance, tissue repair and the improvement of organ function. Allogeneic MSC transplantation for the treatment of SLE and other refractory autoimmune diseases have shown significant efficacy and excellent safety. However, these studies have limitations due to the lack of large-scale, multi-center, randomized, controlled, prospective study to further confirm the efficacy of allogeneic MSC transplantation, as well as the guideline for MSC treatment in SLE needs to be developed. Therefore, a randomized, placebo-controlled, parallel group, non-inferiority, prospective, multicenter clinical trial is urgent needed to promote the application of MSC transplantation in SLE treatment, to bring the benefit of the patients with SLE.
|Study Type :||Interventional|
|Estimated Enrollment :||230 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Double (Participant, Investigator)|
|Official Title:||A Randomized, Double-Blind, Parallel-Controlled, Multi-Center Study to Evaluate the Safety and Efficacy of Human Umbilical Cord Mesenchymal Stem Cells in Patients With Lupus Nephritis|
|Estimated Study Start Date :||August 1, 2018|
|Estimated Primary Completion Date :||June 1, 2021|
|Estimated Study Completion Date :||June 1, 2021|
Experimental: Mesenchymal stem cells
The group receive pulse infusion of MSCs and placebo of oral Mycophenolate Mofetil (MMF). The cells of 2 x 10^6/kg body weight are suspended in 100ml saline and infused intravenously.
Other: Mesenchymal stem cells
The group receive pulse infusion of MSCs once of 2 x 10^6/kg body weight
Drug: Placebo of Mycophenolate Mofetil
The group receive placebo of oral mycophenolate mofetil.
Active Comparator: Mycophenolate Mofetil
The group receive placebo of MSCs and oral Mycophenolate Mofetil of 2.0g/d. .
Drug: Mycophenolate Mofetil
This group receive oral MMF of 2.0 g / d.
Other: Placebo of Mesenchymal stem cells
The group receive placebo of Mesenchymal stem cells.
- Total remission rate [ Time Frame: weeks 24 ]Complete remission rate (CR) and partial remission rate (PR)
- The time for subjects of the two groups to achieve PR and CR [ Time Frame: Baseline to weeks 24 ]
- Levels of 24-hour urinary protein [ Time Frame: Baseline, weeks 4, 8, 12, 16, 20, 24 ]
- Ratio of Urinary Protein / Creatinine [ Time Frame: Baseline, weeks 4, 8, 12, 16, 20, 24 ]
- Levels of serum albumin [ Time Frame: Baseline, weeks 4, 8, 12, 16, 20, 24 ]
- Levels of serum creatinine [ Time Frame: Baseline, weeks 4, 8, 12, 16, 20, 24 ]
- The estimated glomerular filtration rate ( eGFR ) [ Time Frame: Baseline, weeks 4, 8, 12, 16, 20, 24 ]
- Levels of Complement component 3 (C3) [ Time Frame: Baseline, weeks 4, 8, 12, 16, 20, 24 ]
- Levels of Complement component 4 (C4) [ Time Frame: Baseline, weeks 4, 8, 12, 16, 20, 24 ]
- The antinuclear antibody (ANA) levels [ Time Frame: Baseline, weeks 4, 8, 12, 16, 20, 24 ]
- The anti-double stranded DNA antibody (dsDNA) levels [ Time Frame: Baseline, weeks 4, 8, 12, 16, 20, 24 ]
- Patient Health Assessment Questionnaire (HAQ) score [ Time Frame: Baseline, weeks 4, 8, 12, 16, 20, 24 ]
- Physician Global Assessment (PhGA) score [ Time Frame: Baseline, weeks 4, 8, 12, 16, 20, 24 ]
- The (Systemic lupus Erythematosis Disease Activity index) SLEDAI score [ Time Frame: Baseline, weeks 4, 8, 12, 16, 20, 24 ]
- The (British Isles lupus assessment group ) BILAG score [ Time Frame: Baseline, weeks 4, 8, 12, 16, 20, 24 ]
- The SLE reaction index [ Time Frame: Baseline, weeks 4, 8, 12, 16, 20, 24 ]
- Total remission rate [ Time Frame: weeks 12 ]Complete remission rate (CR) and partial remission rate (PR)
- Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 [ Time Frame: Baseline to weeks 24 ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03580291
|Contact: Lingyun Sun, Ph.D M.D.||+86(025)83106666 ext firstname.lastname@example.org|
|The Affiliated Drum Tower Hospital of Nanjing University Medical School||Not yet recruiting|
|Nanjing, Jiangsu, China, 210008|
|Contact: Lingyun Sun, M.D. +86(25)83106666 ext 61421|