Patient-Derived Stem Cell Therapy for Diabetic Kidney Disease

• Sponsor: Mayo Clinic (Other)
• Overall Status: Recruiting
• CT.gov ID: NCT03840343
• Collaborator: Regenerative Medicine Minnesota (Other)
• Enrollment: 30
• Location: 1
• Arms: 2
• Anticipated Duration (Months): 73.3
• Patients Per Site Per Month: 0.4

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Diabetic Kidney Disease; Diabetic Nephropathies; Diabetes Mellitus, Type 2; Diabetes Mellitus, Type 1; Chronic Kidney Disease; Diabetic Nephropathy Type 2; Kidney Failure; Kidney Insufficiency	Biological: Autologous adipose-derived mesenchymal stem/stromal cells (MSC) Lower Dose; Biological: Autologous adipose-derived mesenchymal stem/stromal cells (MSC) Higher Dose	Phase 1

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

1. 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 Design

• Study Type: Interventional
• Anticipated Enrollment: 30 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Intra-arterially Delivered Autologous Mesenchymal Stem/Stromal Cell Therapy in Patients With Diabetic Kidney Disease: A Phase I Study
• Actual Study Start Date: Oct 23, 2019
• Anticipated Primary Completion Date: Dec 1, 2024
• Anticipated Study Completion Date: Dec 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Lower Dose MSC This arm will receive autologous adipose-derived Mesenchymal stem/stromal cells (MSC) Lower Dose.	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
Experimental: Higher Dose MSC This arm will receive autologous adipose-derived Mesenchymal stem/stromal cells (MSC) Higher Dose	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

Outcome Measures

Primary Outcome Measures

1. Adverse Events [Baseline through Month 15]

   The number of Adverse Events associated with MSC intervention per treatment arm

2. Adverse Events [Baseline through Month 15]

   The percentage of Adverse Events associated with MSC intervention per treatment arm

Secondary Outcome Measures

1. Kidney Function [baseline, month 6]

   Change in measured glomerular filtration rate (mGFR). Measured as mL/min/BSA

2. Kidney Function [pretreatment, month 12]

   Change in estimated glomerular filtration rate (eGFR) slope. Measured as mL/min/1.73m^2/month

Eligibility Criteria

Criteria

• Ages Eligible for Study: 45 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic in Rochester	Rochester	Minnesota	United States	55905

Sponsors and Collaborators

• Mayo Clinic
• Regenerative Medicine Minnesota

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• 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

Publications

None provided.

• Responsible Party: LaTonya J. Hickson, Principal Investigator, Mayo Clinic
• ClinicalTrials.gov Identifier: NCT03840343
• Other Study ID Numbers: 18-002423; RMM 091718 CT 001
• First Posted: Feb 15, 2019
• Last Update Posted: Mar 15, 2022
• Last Verified: Mar 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by LaTonya J. Hickson, Principal Investigator, Mayo Clinic: Mesenchymal Stem Cell; Mesencymal Stromal Cell; Stem Cell; Regenerative Medicine; Cell therapy; Rejuvenation
• Additional relevant MeSH terms: Kidney Diseases; Renal Insufficiency, Chronic; Renal Insufficiency; Diabetic Nephropathies; Diabetes Mellitus; Diabetes Mellitus, Type 2; Diabetes Mellitus, Type 1

Study Results

No Results Posted as of Mar 15, 2022