Patient-Derived Stem Cell Therapy for Diabetic Kidney Disease

• ClinicalTrials.gov Identifier: NCT03840343
• Recruitment Status: Recruiting
• First Posted: February 15, 2019
• Last Update Posted: February 26, 2021
• Sponsor: Mayo Clinic
• Collaborator: Regenerative Medicine Minnesota
• Information provided by (Responsible Party): LaTonya J. Hickson, Mayo Clinic

Tracking Information

• First Submitted Date: February 11, 2019
• First Posted Date: February 15, 2019
• Last Update Posted Date: February 26, 2021
• Actual Study Start Date: October 23, 2019
• Estimated Primary Completion Date: December 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 11, 2019)

• Adverse Events [ Time Frame: Baseline through Month 15 ]
  The number of Adverse Events associated with MSC intervention per treatment arm
• Adverse Events [ Time Frame: Baseline through Month 15 ]
  The percentage of Adverse Events associated with MSC intervention per treatment arm

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: February 21, 2019)

• Kidney Function [ Time Frame: baseline, month 6 ]
  Change in measured glomerular filtration rate (mGFR). Measured as mL/min/BSA
• Kidney Function [ Time Frame: pretreatment, month 12 ]
  Change in estimated glomerular filtration rate (eGFR) slope. Measured as mL/min/1.73m^2/month

• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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.
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

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

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
• Biological: 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

Study Arms

• Experimental: Lower Dose MSC
  This arm will receive autologous adipose-derived Mesenchymal stem/stromal cells (MSC) Lower Dose.
  Intervention: Biological: Autologous adipose-derived mesenchymal stem/stromal cells (MSC) Lower Dose
• Experimental: Higher Dose MSC
  This arm will receive autologous adipose-derived Mesenchymal stem/stromal cells (MSC) Higher Dose
  Intervention: Biological: Autologous adipose-derived mesenchymal stem/stromal cells (MSC) Higher Dose

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: February 11, 2019): 30
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 2025
• Estimated Primary Completion Date: December 2024 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 45 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: B Tietje; 507-255-0401; tietje.beverly@mayo.edu

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03840343
• Other Study ID Numbers: 18-002423; RMM 091718 CT 001 ( Other Grant/Funding Number: Regenerative Medicine Minnesota )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: LaTonya J. Hickson, Mayo Clinic
• Study Sponsor: Mayo Clinic
• Collaborators: Regenerative Medicine Minnesota

Investigators

• Principal Investigator: LaTonya J Hickson, MD; Mayo Clinic

• PRS Account: Mayo Clinic
• Verification Date: February 2021