Patient-Derived Stem Cell Therapy for Diabetic Kidney Disease

Diabetes Mellitus, Type 2 Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03840343
• Other study ID #: 18-002423
• Secondary ID: RMM 091718 CT 00
• Status: Terminated
• Phase: Phase 1
• Start date: October 23, 2019
• Est. completion date: August 4, 2020

Study information

• Verified date: April 2023
• Source: Mayo Clinic
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 2
• Est. completion date: August 4, 2020
• Est. primary completion date: August 4, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 45 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Chronic Kidney Disease
• Diabetes Mellitus
• Diabetes Mellitus, Type 1
• Diabetes Mellitus, Type 2
• Diabetic Kidney Disease
• Diabetic Nephropathies
• Diabetic Nephropathy Type 2
• Kidney Diseases
• Kidney Failure
• Kidney Insufficiency
• Renal Insufficiency
• Renal Insufficiency, Chronic

Intervention

Biological:
• Autologous 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
• Autologous 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

Locations

Country	Name	City	State
United States	Mayo Clinic in Rochester	Rochester	Minnesota

Sponsors (2)

Lead Sponsor	Collaborator
Mayo Clinic	Regenerative Medicine Minnesota

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Adverse Events	The number of Adverse Events associated with MSC intervention per treatment arm	Baseline through Month 15
Primary	Adverse Events	The percentage of Adverse Events associated with MSC intervention per treatment arm	Baseline through Month 15
Secondary	Kidney Function	Change in measured glomerular filtration rate (mGFR). Measured as mL/min/BSA	baseline, month 6
Secondary	Kidney Function	Change in estimated glomerular filtration rate (eGFR) slope. Measured as mL/min/1.73m^2/month	pretreatment, month 12

External Links

•   Diabetic Kidney Disease Stem Cell Trial - Mayo Clinic
•   Stem Cells and Kidney Disease - Mayo Clinic
•   Video of Stem Cell Trial in Diabetic Kidney Disease - Regenerative Medicine Minnesota