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

Sponsor

The University of Hong Kong (Other)

Overall Status

Unknown status

CT.gov ID

NCT02954939

Collaborator

(none)

Enrollment

Location

Arms

Anticipated Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Lupus Nephritis	Drug: MMF-MMF Drug: CTX-AZA	N/A

Detailed Description

Study Design

Study Type:

Interventional

Anticipated Enrollment :

50 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Basic Science

Official Title:

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

Actual Study Start Date :

Mar 1, 2017

Anticipated Primary Completion Date :

Mar 1, 2021

Anticipated Study Completion Date :

Jun 1, 2021

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: MMF-MMF 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 Class III/IV+/-V lupus nephritis patients to receive PRED+MMF Other Names: PRED; MMF
Placebo Comparator: CTX-AZA 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 Class III/IV+/-V lupus nephritis patients to receive PRED+CTX followed by AZA Other Names: PRED; CTX; AZA

Arm

Intervention/Treatment

Active Comparator: MMF-MMF

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

Class III/IV+/-V lupus nephritis patients to receive PRED+MMF

Other Names:

PRED; MMF

Placebo Comparator: CTX-AZA

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

Class III/IV+/-V lupus nephritis patients to receive PRED+CTX followed by AZA

Other Names:

PRED; CTX; AZA

Outcome Measures

Primary Outcome Measures

Lymphocyte subset profile (CD8+ T cells, CD4+ Th1, Th2, Th17 & Treg), Naïve & memory B cells, plasma cells [48 weeks]

Secondary Outcome Measures

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

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