Use of Wharton Jelly in Diabetic Nephropathy

Study Overview
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Brief Summary
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Wharton Jelly derived Mesenchymal stem cells will be injected in the renal parenchyma of patients with Diabetic Nephropathy

Detailed Description
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Mesenchymal stem cells (MSCs) are to be isolated from Umbilical cord Wharton's Jelly obtained after normal full term delivery. Samples will be tested for any bacterial or fungal growth as well as endotoxin and mycoplasma. The specific markers for MSCs identification will be analyzed by flow cytometry. Cell suspension will then be injected in the renal parenchyma of patients diagnosed with diabetic nephropathy.

Official Title
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The Safety of Intra-parenchymal Wharton Jelly Mesenchymal Stem Cell Injection in the Treatment of Diabetic Nephropathy

Conditions
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Diabetic Nephropathies

Intervention / Treatment
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* Biological: Wharton Jelly Mesenchymal stem cells


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Willing and able to provide written informed consent. Type 2 diabetes mellitus (DM) for ≥ 3 years. Estimated GFR (eGFR) 15-45 ml/min/1.73 m2 by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation on 2 or more consecutive measurements at least 30 days apart within the past 6 months, confirmed by isotope kidney scan. Urine protein-to-creatinine ratio (UPCR) ≥ 500 mg/mmol (in spot urine or in 24 hour urine collection) confirmed twice over a period of 6 months. Ultrasonographic kidney measurements ≥ 10 cm (for both kidneys). Exclusion Criteria: Patients with uncontrolled hyper or hypo tension; (systolic pressure >160, <100: diastolic pressure < 60, >100) on two different occasions. Poor diabetic control: Hemoglobin A1c (HbA1c) > 10%. New use of hypoglycemic, antihypertensive and/or lipid lowering agent within the past 6 months. Increase in the dose of anti-hypertensive and/or hypoglycemic agent of the previous dose within the past 3 months. Current fasting total cholesterol >300 mg/dl. Current fasting total triglycerides >400 mg/dl. History of any cardiovascular events in the past 6 months. Pregnancy or lactating. Positive screening test for infectious diseases as per baseline work up. History of kidney transplant Systemic autoimmune disease. Receiving immunosuppressant medications. Patients with glomerulonephritis or any non-DM related kidney disease. Patients with any coagulation disorder.

Ages Eligible for Study
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Minimum Age: 35 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Wharton Jelly Mesenchymal stem cells<br>Intervention: Wharton Jelly Mesenchymal stem cells Site: Renal parenchyma Route of administration: ultrasound guided- intra-parenchymal total of 3 sites in each kidney. Number of doses: 3 doses 2 weeks apart for each kidney. Time interval between each dose: 2 weeks Total volume of cell suspension infused: 3 ml/kidney; each site will receive a 1 ml cell suspension with a total volume of 3 ml in each kidney. | Biological: Wharton Jelly Mesenchymal stem cells<br>* Wharton Jelly Mesenchymal stem cells will be injected in the renal parenchyma<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] | Number, frequency and severity of injection associated adverse events. The nephrologist will record any adverse event at each follow up visit in addition to evaluation of the overall condition of the patient. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of the preliminary efficacy of the injection on kidney's Estimated Glomerular filtration rate | • Any positive changes in the patient's kidney function in terms of Estimated Gomerular filtration rate (mL/min/1.73 m²) | 12 months | 
| Evaluation of the preliminary efficacy of the injection on kidney's protein to creatinine ratio | Any positive changes in the patient's kidney function in terms of Urine protein to creatinine ratio. | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diabetes, nephropathy, Kidney, parenchyma, Wharton Jelly, Mesenchymal stem cells