Clinical trial NCT03840343: Patient-Derived Stem Cell Therapy for Diabetic Kidney Disease
Official title: Intra-arterially Delivered Autologous Mesenchymal Stem/Stromal Cell Therapy in Patients With Diabetic Kidney Disease: A Phase I Study
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Diabetic Kidney Disease
Diabetic Nephropathies
Diabetes Mellitus, Type 2
Diabetes Mellitus, Type 1
Chronic Kidney Disease
Diabetic Nephropathy Type 2
Kidney Failure
Kidney Insufficiency
Keywords: Mesenchymal Stem Cell
Mesencymal Stromal Cell
Stem Cell
Regenerative Medicine
Cell therapy
Rejuvenation
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
Collaborators: name: Regenerative Medicine Minnesota
First posted: 2019-02-15
Enrollment: 2
Sex: ALL
Minimum age (years): 45
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Adverse Events
timeFrame: Baseline through Month 15
measure: Adverse Events
timeFrame: Baseline through Month 15
Secondary outcomes:
measure: Kidney Function
timeFrame: baseline, month 6
measure: Kidney Function
timeFrame: pretreatment, month 12
Other outcomes:
Locations:
city: Rochester
country: United States
facility: Mayo Clinic in Rochester
state: Minnesota
Study officials:
affiliation: Mayo Clinic
name: LaTonya J Hickson, MD
role: PRINCIPAL_INVESTIGATOR
References: