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Allogenic AD-MSC Transplantation in Idiopathic Nephrotic Syndrome (Focal Segmental Glomerulosclerosis)

Phase 1
Conditions
Focal Segmental Glomerulosclerosis
Interventions
Biological: Intravenous injection
Registration Number
NCT02382874
Lead Sponsor
Royan Institute
Brief Summary

Idiopathic Focal Segmental Glumero Sclerosis (FSGS) is not very common but important manifestation of kidney disease.

FSGS has poor prognosis among the patterns of Idiopathic Nephrotic Syndrome (INS).

Even with treatment (Steroid therapy and cytotoxic immunosuppressant therapy), many patients eventually still require dialysis.

Cell therapy is useful in treatment of INS and mesenchymal stromal/stem cell is one of the cells that useful in the treatment of glomerulus disease.

Intravenous injection of allogeneic adipose derived mesenchymal stromal/stem cell will be done in 5 patients with refractory INS(FSGS). They will be followed 1, 2, 4 weeks and then monthly until a year following injection day.

Detailed Description

Primary FSGS thought to be a part of the immune-mediated disease. Main challenge is to decrease protein excretion in urine. Only 30% of children with FSGS achieve complete remission with steroids and other 30-40% patients experience remission (partial and complete) with cytotoxic immunosuppressant drugs. Even with these treatments, many patients eventually still require dialysis. Other treatment strategy doesn't exceed beyond symptomatic treatment and delaying the progression. Also risk of recurrence after kidney transplantation is 20-50%.

Cell therapy is one of the treatment strategies and mesenchymal stromal/stem cell is one modality that notice in glomerulus disease.

We will evaluate safety and efficacy of intravenous injection of allogeneic AD-MSC (adipose-derived mesenchymal stromal cell) in 5 refractory INS patients.They will be followed 1, 2, 4 weeks and then monthly until a year following injection day.

Recruitment & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
5
Inclusion Criteria
  • Age 2-14 years at onset of signs or symptoms of FSGS 2- Primary FSGS involving either native kidneys or primary FSGS recurring after renal transplantation. Biopsy confirmed as primary FSGS (including all subtypes).

3-Estimated GFR ≥ 25 ml/min/1.73 m2 4- Up/c > 1.0 (g protein/g creatinine) on first am void 5- Steroid and IS resistance as defined by primary physician (patients with little or no reduction in protein excretion at 12 to 16 weeks are considered to be steroid resistant --A relapse is return of proteinuria to ≥3.5 g/day in someone who had undergone a complete or partial remission- IS resistance: no response to IS in 8-12 weeks) 6-At least one month from last immunization received has passed 7- Ability to understand and willingness to sign consent by patient legal guardian

Exclusion Criteria
  • 1- Are immunodeficient or have clinically significant chronic lymphopenia 2-Have an active infection or positive PPD test result 3-Have serologic evidence of current or past HIV, Hepatitis B, or Hepatitis C infection 4-Have any complicating medical issues that interfere with study conduct or cause increased risk such as malignancies, systemic autoimmune disease, diabetes, blood disease, liver disease, etc.

5- Positive genetic mutation testing for WT1, Podocin, Nephrin

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
AD-MSCIntravenous injectionThe patients with FSGS who underwent intravenous injection of AD-MSC.
Primary Outcome Measures
NameTimeMethod
Liver function2 weeks

increase of liver enzymes 2 weeks after cell injection.

Serum creatinine2 weeks

Decrease of serum creatinine 2 weeks after cell injection.

Proteinuria12 hour

Reduction in proteinuria to \<200 to 300 mg/day will be assessed by Changes in 24 hour urine protein analysis.

Secondary Outcome Measures
NameTimeMethod
Renal function12 hours

will be assessed by change in serum levels of Cr, Urea and GFR. Time Frame: 12 hr after injection,1,2 weeks then monthly until a year after 1st injection.

Increase in anti inflammatory factors12 hours

It will be assessed by change in serum levels of IL-2, 10. Time frame: 12 hour after injection then monthly until a year 1st injection.

Increase in Treg12hours

It will be assessed by change in serum levels of Treg. Time frame: 12 hr after injection,1 week, 3, 6,12 months after 1st injection.

Trial Locations

Locations (1)

Royan Institute

🇮🇷

Tehran, Iran, Islamic Republic of

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