Effect of Mesenchymal Stem Cell Transplantation for Lupus Nephritis

Mesenchymal Stem Cell (MSC) has been shown to have immunosuppressive and repairing properties. Manifestations of systemic lupus eryhematosus(SLE) may in most patients be ameliorated with medications that suppress the immune system. Nevertheless, there remains a subset of SLE patients for whom current strategies are insufficient to control disease. The investigators will infuse expanded autologous MSC into patients with lupus Nephritis. The purpose of this trial is to evaluate whether this new therapeutical approach will result in improvement in the lupus disease.

Study Overview

• Status: Unknown
• Conditions: Lupus Nephritis
• Intervention / Treatment: Biological: mesenchymal stem cell

Detailed Description

Mesenchymal stem cells (MSC), or marrow stromal cells, are multipotential cells that reside within the bone marrow and can be induced to differentiate into various components of the marrow microenvironment, such as bone, adipose and stromal tissues under proper conditions. It has been reported that MSCs can suppress maturation, activation and proliferation of T, B, NK and DC cell in vitro and downregulate immune response in vivo. MSCs are presently being cotransplantated with hematopoietic stem cell, which can facilitates engraftment of hematopoietic stem cells and prevent GVHD. Systemic lupus erythematosus (SLE) is an autoimmune disorder that affects many organ systems. Autoimmune diseases are illnesses that occur when the body's tissues are attacked by its own immune system. Patients with lupus produce abnormal antibodies in their blood that target tissues within their own body. Because the antibodies and accompanying cells of inflammation can involve tissues anywhere in the body, lupus has the potential to affect a variety of areas of the body. The origin of autoantibody production in SLE is unclear but a role has been suggested for an antigen driven process, spontaneous B-cell hyper-responsiveness, or impaired immune regulation.

The BXSB mouse strain spontaneously develops a progressive and lethal autoimmune disease, similar to human SLE. In our previous work we found that transplantation of MSCs could alleviate the symptoms of BXSB mouse.

This study will evaluate the safety and effectiveness of expanded autologous MSC infusions in patients with primary and treatment -refractory SLE. This study will last 2 years. Participants will be assigned to receive either the prednisone (Group 1) or MSC infusions alone (Group 2). Patients will undergo MSC infusions at the start of the study on Day 0. One year post- infusions, Patients will be clinically assessed and evaluated for MSC and disease response, and participants will undergo kidney biopsies at 12 Months.

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Jianming Tan, Professor JM Tan, doctor; Phone Number: 008613375918000; Email: doctortjm@YAHOO.COM

Study Locations

• China
  • Fujian
    • Fuzhou, Fujian, China, 350025
      • Fuzhou General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Ages 18 to 50 years old.
2. Meet at least 4 of 11 American College of Rheumatology (ACR) Classification criteria for SLE.
3. Able to give informed consent.
4. For treatment -refractory lupus nephritis, participants must fail pulse cyclophosphamide, a renal biopsy must be obtained and document either class III or IV glomerulonephritis.

Exclusion Criteria:

1. Pregnant women.
2. Previous history of malignancy
3. Active infection including hepatitis B, hepatitis C, HIV, or TB as determined by a positive skin test or clinical presentation, or under treatment for suspected TB.
4. Evidence of cardiovascular disease, existing congestive cardiac failure on physical exam and/or acute coronary syndrome in past 6 months.
5. Psychiatric illness or mental deficiency making compliance with treatment or informed consent impossible.
6. Transaminases greater than 2 times normal unless due to active lupus.
7. Any illness that in the opinion of the investigator would jeopardize the ability of the Patient to tolerate this treatment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 2; mesenchymal stem cell Autologous MSC transplantation	Biological: mesenchymal stem cell; Autologous MSC transplantation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
the proportion of participants who achieve and maintain remission	5

Secondary Outcome Measures

Outcome Measure	Time Frame
Patient survival	5
Creatinine and proteinuria.	5
SLE disease activity index	5
Serology (ANA, dsDNA)	5
ComplementC3 and C4	5

Collaborators and Investigators

• Sponsor: Organ Transplant Institute, China

Study record dates

Study Major Dates

• Study Start: May 1, 2008
• Primary Completion (Anticipated): May 1, 2010
• Study Completion (Anticipated): May 1, 2010

Study Registration Dates

• First Submitted: April 14, 2008
• First Submitted That Met QC Criteria: April 14, 2008
• First Posted (Estimate): April 16, 2008

Study Record Updates

• Last Update Posted (Estimate): April 16, 2008
• Last Update Submitted That Met QC Criteria: April 14, 2008
• Last Verified: April 1, 2008

More Information

Terms related to this study

• Keywords: Mesenchymal Stem Cells; lupus Nephritis
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Kidney Diseases; Urologic Diseases; Connective Tissue Diseases; Glomerulonephritis; Lupus Erythematosus, Systemic; Nephritis; Lupus Nephritis
• Other Study ID Numbers: fuzhough0713