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

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

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.

Study Overview

• Status: Unknown
• Conditions: Focal Segmental Glomerulosclerosis
• Intervention / Treatment: Biological: Intravenous injection

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.

• Study Type: Interventional
• Enrollment (Anticipated): 5
• Phase: Phase 1

Contacts and Locations

Study Locations

• Iran, Islamic Republic of
  • Tehran, Iran, Islamic Republic of
    • Recruiting
    • Royan Institute
    • Contact: Nasser Aghdami, MD,PhD; Phone Number: 516 (+98)2123562000; Email: nasser.aghdami@royaninstitute.org
    • Contact: Leila Arab, MD; Phone Number: 414 (+98)2123562000; Email: Leara91@gmail.com
    • Principal Investigator: Reza Moghadasali, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 14 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 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: AD-MSC; The patients with FSGS who underwent intravenous injection of AD-MSC.	Biological: Intravenous injection; Intravenous injection of AD-MSC to the patients with FSGS

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Liver function	increase of liver enzymes 2 weeks after cell injection.	2 weeks
Serum creatinine	Decrease of serum creatinine 2 weeks after cell injection.	2 weeks
Proteinuria	Reduction in proteinuria to <200 to 300 mg/day will be assessed by Changes in 24 hour urine protein analysis.	12 hour

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Renal function	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.	12 hours
Increase in anti inflammatory factors	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.	12 hours
Increase in Treg	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.	12hours

Collaborators and Investigators

• Sponsor: Royan Institute
• Investigators: Study Director: Nasser Aghdami, MD,PhD, Head of department of regenerative medicine&cell therapy center,Royan Institute; Study Director: Hassan Otukesh, MD, Department Of Pediatric Nephrology and Dialysis, Ali aghar Children Hospital, Iran University of Medical Sciences, Tehran, Iran; Principal Investigator: Rozita Hosseini, MD, Department Of Pediatric Nephrology and Dialysis, Ali aghar Children Hospital, Iran University of Medical Sciences, Tehran, Iran; Principal Investigator: Soroosh Shekarchian, MD, Department of Regenerative Biomedicine at the Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran.

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: May 1, 2015
• Primary Completion (Anticipated): June 1, 2017
• Study Completion (Anticipated): October 1, 2017

Study Registration Dates

• First Submitted: March 3, 2015
• First Submitted That Met QC Criteria: March 6, 2015
• First Posted (Estimate): March 9, 2015

Study Record Updates

• Last Update Posted (Estimate): December 4, 2015
• Last Update Submitted That Met QC Criteria: December 3, 2015
• Last Verified: November 1, 2015

More Information

Terms related to this study

• Keywords: Focal segmental glomerulosclerosis; Idiopathic nephrotic syndrome; adipose derived mesenchymal stromal cell
• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Nephritis; Glomerulonephritis; Glomerulosclerosis, Focal Segmental; Nephrotic Syndrome; Nephrosis
• Other Study ID Numbers: Royan-Kidney-005