Title
Patient-Derived Stem Cell Therapy for Diabetic Kidney Disease
Intra-arterially Delivered Autologous Mesenchymal Stem/Stromal Cell Therapy in Patients With Diabetic Kidney Disease: A Phase I Study
Phase
Phase 1Lead Sponsor
Mayo ClinicStudy Type
InterventionalStatus
RecruitingStudy Participants
30The 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).
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.
Two MSC infusions of 2.5x10^5 cells/kg at time zero and three months; single kidney, intra-arterial delivery
Two MSC infusions of 5.0x10^5 cells/kg at time zero and three months; single kidney, intra-arterial delivery
This arm will receive autologous adipose-derived Mesenchymal stem/stromal cells (MSC) Lower Dose.
This arm will receive autologous adipose-derived Mesenchymal stem/stromal cells (MSC) Higher Dose
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
