Patient-Derived Stem Cell Therapy for Diabetic Kidney Disease

Study Overview
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Brief Summary
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The Researchers will assess the safety, tolerability, dosing effect, and early signals of efficacy of intra-arterially delivered autologous (from self) adipose (fat) tissue-derived mesenchymal stem/stromal cells (MSC) in patients with progressive diabetic kidney disease (DKD).

Detailed Description
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This is a single center, open-label dose-escalating study assessing safety, tolerability, dosing effect, and early signals of efficacy of intra-arterially delivered autologous (from self) adipose tissue-derived mesenchymal stem/stromal cells (MSC) in 30 patients with progressive diabetic kidney disease (DKD). DKD will be defined as chronic kidney disease (CKD; estimated glomerular filtration rate; eGFR<60 mL/min/1.73m2) in the setting of diabetes mellitus (type 2; on anti-diabetes therapy) without overt etiologies of CKD beyond concomitant hypertension. Progressive DKD will be considered as eGFR 25-55 ml/min/1.73m2 with a) eGFR decline of 5 ml/min over 18 months or 10 ml/min over 3 years or b) an intermediate or high 5-year risk of progression to end-stage kidney failure (dialysis or transplant) based on the validated Tangri 4-variable (age, sex, eGFR, urinary albumin-creatinine ratio) kidney failure risk equation. Fifteen subjects will be placed in one of two cell dosage arms in a parallel design with single-kidney MSC administration at Day 0 and Month 3. Subjects will be followed a total of 15 months from time of initial cell administration.

Official Title
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Intra-arterially Delivered Autologous Mesenchymal Stem/Stromal Cell Therapy in Patients With Diabetic Kidney Disease: A Phase I Study

Conditions
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Kidney Insufficiency, Diabetic Kidney Disease, Diabetic Nephropathies, Diabetes Mellitus, Type 2, Diabetes Mellitus, Type 1, Chronic Kidney Disease, Diabetic Nephropathy Type 2, Kidney Failure

Intervention / Treatment
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* Biological: Autologous adipose-derived mesenchymal stem/stromal cells (MSC) Lower Dose
* Biological: Autologous adipose-derived mesenchymal stem/stromal cells (MSC) Higher Dose


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diabetes mellitus (on anti-diabetes drug therapy) Age 45-75 years eGFR 25-55 ml/min/1.73m2 at time of consent with: a) eGFR decline of 5 ml/min over 18 months or 10 ml/min over 3 years or b) an intermediate or high 5-year risk of progression to end-stage kidney failure (dialysis or transplant) based on the validated Tangri 4-variable (age, sex, eGFR, urinary albumin-creatinine ratio) kidney failure risk equation https://kidneyfailurerisk.com/ Primary cause of kidney disease is diabetes without suspicion of concomitant kidney disease beyond hypertension Spot urine albumin:creatinine ≥30 mg/g unless on RAAS inhibition Ability to give informed consent Exclusion Criteria: Hemoglobin A1c≥11% Pregnancy Active malignancy Active Immunosuppression therapy Kidney transplantation history Concomitant glomerulonephritis Nephrotic syndrome Solid organ transplantation history Autosomal dominant or recessive polycystic kidney disease Known renovascular disease Kidney failure (hemodialysis, peritoneal dialysis, or kidney transplantation) Active tobacco use Body weight >150 kg or BMI>50 Uncontrolled hypertension: Systolic blood pressure (SBP) >180 mmHg despite antihypertensive therapy Recent cardiovascular event (myocardial infarction, stroke, congestive heart failure within 6 months Evidence of hepatitis B or C, or HIV infection, chronic Anticoagulation therapy requiring heparin bridging for procedures. History of methicillin-resistant staphylococcus aureus colonization Recent plastic, chemical or surgical manipulation of adipose tissue for cosmetic purposes within 6 months Inability to give informed consent Potentially unreliable subjects and those judged by the investigator to be unsuitable for the study

Ages Eligible for Study
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Minimum Age: 45 Years
Maximum Age: 75 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
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lower Dose MSC<br>This arm will receive autologous adipose-derived Mesenchymal stem/stromal cells (MSC) Lower Dose. | Biological: Autologous adipose-derived mesenchymal stem/stromal cells (MSC) Lower Dose<br>* Two MSC infusions of 2.5x10^5 cells/kg at time zero and three months; single kidney, intra-arterial delivery<br>|
| Experimental: Higher Dose MSC<br>This arm will receive autologous adipose-derived Mesenchymal stem/stromal cells (MSC) Higher Dose | Biological: Autologous adipose-derived mesenchymal stem/stromal cells (MSC) Higher Dose<br>* Two MSC infusions of 5.0x10^5 cells/kg at time zero and three months; single kidney, intra-arterial delivery<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse Events | The number of Adverse Events associated with MSC intervention per treatment arm | Baseline through Month 15 | 
| Adverse Events | The percentage of Adverse Events associated with MSC intervention per treatment arm | Baseline through Month 15 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Kidney Function | Change in measured glomerular filtration rate (mGFR). Measured as mL/min/BSA | baseline, month 6 | 
| Kidney Function | Change in estimated glomerular filtration rate (eGFR) slope. Measured as mL/min/1.73m^2/month | pretreatment, month 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Mesenchymal Stem Cell, Mesencymal Stromal Cell, Stem Cell, Regenerative Medicine, Cell therapy, Rejuvenation