Clinical trial NCT02382874: Allogenic AD-MSC Transplantation in Idiopathic Nephrotic Syndrome (Focal Segmental Glomerulosclerosis)
Official title: Allogenic Adipose Derived Mesenchymal Stromal Cells Transplantation to Improve Kidney Function in Refractory Primary Nephrotic Syndrome (Focal Segmental Glomerulosclerosis,FSGS) ,a Phase I Clinical Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Focal Segmental Glomerulosclerosis
Keywords: Idiopathic nephrotic syndrome
adipose derived mesenchymal stromal cell
Focal segmental glomerulosclerosis
Lead sponsor: Royan Institute
Sponsor class: OTHER_GOV
First posted: 2015-03-09
Enrollment: 5
Sex: ALL
Minimum age (years): 2
Maximum age (years): 14
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Liver function
timeFrame: 2 weeks
measure: Serum creatinine
timeFrame: 2 weeks
measure: Proteinuria
timeFrame: 12 hour
Secondary outcomes:
measure: Renal function
timeFrame: 12 hours
measure: Increase in anti inflammatory factors
timeFrame: 12 hours
measure: Increase in Treg
timeFrame: 12hours
Other outcomes:
Locations:
city: Tehran
country: Iran, Islamic Republic of
facility: Royan Institute
Study officials:
affiliation: Head of Royan Institute
name: Hamid Gourabi, PhD
role: STUDY_CHAIR
affiliation: Head of department of regenerative medicine&cell therapy center,Royan Institute
name: Nasser Aghdami, MD,PhD
role: STUDY_DIRECTOR
affiliation: Department Of Pediatric Nephrology and Dialysis, Ali aghar Children Hospital, Iran University of Medical Sciences, Tehran, Iran
name: Hassan Otukesh, MD
role: STUDY_DIRECTOR
affiliation: Department Of Pediatric Nephrology and Dialysis, Ali aghar Children Hospital, Iran University of Medical Sciences, Tehran, Iran
name: Rozita Hosseini, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of Regenerative Biomedicine at the Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran.
name: Soroosh Shekarchian, MD
role: PRINCIPAL_INVESTIGATOR
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