The Effect of Mycophenolate Mofetil and Cyclophosphamide on the Lymphocyte Subsets in Patients With Proliferative Lupus Nephritis

Study Overview
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Brief Summary
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This study investigated the effect of mycophenolate mofetil and cyclosphosphamide on lymphocyte subsets in patients with proliferative lupus nephritis. Patients with biopsy-proven Class III/IV+/-V LN were randomized to received: 1) prednisolone (0.8mg/kg/day) plus CTX (1.5-2mg/kg/d) for 6 months) followed by Azathioprine (AZA) (1-1.5mg/kg/d) maintenance; OR 2) prednisolone (0.8mg/kg/d) plus MMF (1g bd) for 6 months, followed by MMF (tapered according to clinical status) as maintenance. The lymphocyte subsets and serum cytokine profiles will be measured at 4-, 12-, and 24-, 36- and 48 weeks after induction treatment. The lymphocyte subsets and serum cytokine profiles will be compared between the two treatment regimens, and also correlated with subsequent risk of relapse.

Detailed Description
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This study investigated the effect of mycophenolate mofetil and cyclosphosphamide on lymphocyte subsets in patients with proliferative lupus nephritis. Patients with biopsy-proven Class III/IV+/-V LN were randomized to received: 1) prednisolone (0.8mg/kg/day) plus CTX (1.5-2mg/kg/d) for 6 months) followed by Azathioprine (AZA) (1-1.5mg/kg/d) maintenance; OR 2) prednisolone (0.8mg/kg/d) plus MMF (1g bd) for 6 months, followed by MMF (tapered according to clinical status) as maintenance. The lymphocyte subsets and serum cytokine profiles will be measured at 4-, 12-, and 24-, 36- and 48 weeks after induction treatment. The lymphocyte subsets and serum cytokine profiles will be compared between the two treatment regimens, and also correlated with subsequent risk of relapse.

Official Title
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The Effect of Mycophenolate Mofetil and Cyclophosphamide on the Lymphocyte Subsets and Relationship With Relapse

Conditions
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Lupus Nephritis

Intervention / Treatment
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* Drug: MMF-MMF
* Drug: CTX-AZA


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: - 1. Patients with biopsy proven Class III/IV+/-V LN (ISN/RPS classification) and active nephritis as indicated by an increase of proteinuria >1g/day and/or rise in serum creatinine by >15% compared with baseline, with or without serological reactivation. 2. Willing to give informed consent Exclusion Criteria: Patients who have received calcineurin inhibitors or proliferation signal inhibitors as maintenance immunosuppression in the preceding 3 months Patients have received biologics therapy (e.g. rituximab, abatacept) in the preceding 12 months Patients who are pregnant or lactating

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: MMF-MMF<br>Class III/IV+V LN patients who receive prednisolone (PRED) (0.8mg/kg/d) plus mycophenolate mofetil (MMF) (1g bd) as induction-maintenance therapy | Drug: MMF-MMF<br>* Class III/IV+/-V lupus nephritis patients to receive PRED+MMF<br>* Other names: PRED; MMF;|
| Placebo Comparator: CTX-AZA<br>Class III/IV+V LN patients who receive prednisolone (PRED) (0.8mg/kg/d) plus Cyclophosphamide (CTX) (1.5-2mg/kg/d) followed by Azathioprine (AZA) (1-1.5mg/kg/d) as induction-maintenance therapy | Drug: CTX-AZA<br>* Class III/IV+/-V lupus nephritis patients to receive PRED+CTX followed by AZA<br>* Other names: PRED; CTX; AZA;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Lymphocyte subset profile (CD8+ T cells, CD4+ Th1, Th2, Th17 & Treg), Naïve & memory B cells, plasma cells |  | 48 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| serum cytokine profile (IL-2, IL-5, IL-6, IL-7, IL-10, IL-17, IL-21, IL-23, IFN-alpha, IFN-gamma, TGF-beta) |  | 48 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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lupus nephritis, lymphocyte subsets, cytokines, mycophenolate mofetil, cyclophosphamide