Chronic Kidney Disease, Diabetes Mellitus, Type 1, Diabetes Mellitus, Type 2, Diabetic Kidney Disease, Diabetic Nephropathies, Diabetic Nephropathy Type 2, Kidney Failure, Kidney Insufficiency
Conditions
Keywords
Mesenchymal Stem Cell, Mesencymal Stromal Cell, Stem Cell, Regenerative Medicine, Cell therapy, Rejuvenation
Brief summary
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
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.
Interventions
BIOLOGICALAutologous adipose-derived mesenchymal stem/stromal cells (MSC) Lower Dose
Two MSC infusions of 2.5x10\^5 cells/kg at time zero and three months; single kidney, intra-arterial delivery
BIOLOGICALAutologous adipose-derived mesenchymal stem/stromal cells (MSC) Higher Dose
Two MSC infusions of 5.0x10\^5 cells/kg at time zero and three months; single kidney, intra-arterial delivery
Sponsors
Regenerative Medicine Minnesota
Mayo Clinic
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
45 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adverse Events | Baseline through Month 15 | The number of Adverse Events associated with MSC intervention per treatment arm |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Kidney Function | baseline, month 6 | Change in measured glomerular filtration rate (mGFR). Measured as mL/min/BSA |
Countries
United States
Outcome results
None listed