Renal Insufficiency, ChronicPhase 2CKDNCT02966717
Rituximab Combined With MSCs in the Treatment of PNS (3-4 Stage of CKD)
A Phase 2 study testing Rituximab, conventional therapy and Mesenchymal stem cells in people with Renal Insufficiency, Chronic and Nephrotic Syndrome, run by Zhujiang Hospital at 1 site in China.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Renal Insufficiency, Chronic, Nephrotic Syndrome
- What is being tested?
- Rituximab, conventional therapy and Mesenchymal stem cells
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 116 participants
- Where
- 1 siteChina
- Study dates
- Aug 2016to Oct 2021
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
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.
-
Trial locations and contacts
1 site in 1 country.
China1 site
Zhujiang Hospital, Southern Medical University
Guangzhou, Guangdong, 510282
About this study
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)
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.
Read the 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.
- Conditions
- Renal Insufficiency, Chronic, Nephrotic Syndrome
- Being tested
- Rituximab, conventional therapy, Mesenchymal stem cells
- Keywords
- Rituximab, Mesenchymal stem cells, primary nephrotic syndrome, chronic kidney disease
- Medical subject headings
- Renal Insufficiency, Chronic, Nephrotic Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RituximabDrug
Also called Mabthera, RTX, Rituxan
Rituximab is a human-mouse-chimeric monoclonal antibody which was approved in 1997 for the treatment of cancer.
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.
Mesenchymal stem cellsDrug
Also called MSCs
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.
| Study group | Role | What they receive |
|---|---|---|
| parallel control of conventional therapy | Active comparator | 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. Receives: Drug: conventional therapy |
| experimental group | Experimental | 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. Receives: Drug: Rituximab; Drug: Mesenchymal stem cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
The change of serum creatinine elevation
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.
Measured: 4 weeks, 8 weeks, 12 weeks
The percentage of end-stage renal disease or death.
The percentage of end-stage renal disease or death should be less than 60%.
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Nov 2016 (estimated)
- Study startAug 2016
- Primary completionOct 2016
- Study completionOct 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Renal Insufficiency, ChronicStudies of the same condition, open and under way.
- More trials run by Zhujiang HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 116 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Zhujiang Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Tang Xun, doctor, Principal investigator, Zhujiang Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02966717
- Sponsor's protocol ID
- Tangxun8022
- Acronym
- CKD
- Status last verified
- Nov 2016
- First submitted
- 30 Oct 2016
- Last updated
- 22 Nov 2016
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 22 Nov 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT02966717
- Acronym / sponsor ID
- CKD / Tangxun8022
- Conditions
- Renal Insufficiency, Chronic, Nephrotic Syndrome
- Keywords
- Rituximab, Mesenchymal stem cells, primary nephrotic syndrome, chronic kidney disease
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 116 participants (estimated)
- Lead sponsor
- Zhujiang HospitalUniversity, hospital or other
- Study start
- Aug 2016
- Primary completion
- Oct 2016 (actual)
- Study completion
- Oct 2021 (estimated)
- First posted
- 17 Nov 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| parallel control of conventional therapy | Active comparator | Drug: conventional therapyIntervention 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. |
| experimental group | Experimental | Drug: Rituximab, Drug: Mesenchymal stem cellsIntervention 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. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RituximabAlso: Mabthera, RTX, RituxanRituximab is a human-mouse-chimeric monoclonal antibody which was approved in 1997 for the treatment of cancer. | Drug | experimental group |
| conventional therapyIntervention 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 | parallel control of conventional therapy |
| Mesenchymal stem cellsAlso: MSCsMesenchymal 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. | Drug | experimental group |
Primary outcome
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%.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Nov 2016.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Tang Xun, doctor principal investigator
Zhujiang Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Rituximab, conventional therapy and Mesenchymal stem cells in people with Renal Insufficiency, Chronic and Nephrotic Syndrome, run by Zhujiang Hospital at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 22 Nov 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The change of serum creatinine elevation (time frame: 4 weeks, 8 weeks, 12 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Nov 2016.