Bone Marrow-Derived Mesenchymal Stem Cell Therapy for Chronic Kidney Disease

The purpose of this study is to assess the safety and tolerability of intravenously delivered mesenchymal steml cells (MSC) in one of two fixed dosing regimens at two time points in patients with chronic kidney disease.

Study Overview

• Status: Completed
• Conditions: Chronic Kidney Diseases
• Intervention / Treatment: Drug: Allogeneic adipose-derived mesenchymal stem cells (MSC); Drug: Allogeneic adipose-derived mesenchymal stem cells (MSC)

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic Florida
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic Rochester

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age 30-80 years

2. Estimated glomerular filtration rate (eGFR) 25-55 ml/min/1.73m2

   1. If eGFR 45-55 ml/min/1.73m2, then albumin:creatinine ratio ≥300 mg/g or proteinuria ≥300 mg/day despite maximally tolerated dose of RAAS drugs (e.g. ACE Inhibitors, Angiotensin Receptor Blockers)
   2. If eGFR 25-44 ml/min/1.73m2, must have urine albumin:creatinine ratio ≥30mg/g despite maximally tolerated dose of RAAS drugs (e.g. ACE Inhibitors, Angiotensin Receptor Blockers)
3. Hemoglobin A1c of ≤ 8% despite maximally tolerated anti-diabetes therapy
4. Ability to give informed consent

Exclusion Criteria:

1. Anemia (hemoglobin <9 g/dL)
2. Body weight >150 kg or BMI >50
3. Uncontrolled hypertension: sustained systolic blood pressure (SBP) >150 mmHg or diastolic blood pressure (DBP) ≥100 mmHg despite maximal doses of at least 2 different classes of anti-hypertensive medications
4. Chronic hypotension history: sustained SBP <85 mmHg
5. Glomerulonephritis not in partial or complete remission for 6 months (or estimated/ measured proteinuria greater than 10 grams/day),
6. Active glomerulonephritis (glomerular diseases with evidence of active urinary sediment, serology or biopsy findings) including ANCA-associated glomerulonephritis, post-infectious glomerulonephritis, lupus nephritis, amyloidosis, or other monoclonal gammopathy of renal significance
7. Autosomal dominant or recessive polycystic kidney disease
8. Nephrotic syndrome defined as proteinuria >3.5 g per 24 hours, plus hypoalbuminemia (serum albumin less than or equal to 2.5 g/L) and edema.
9. Proteinuria >5 g/day (with or without nephrotic syndrome).
10. Kidney failure requiring renal replacement therapy (hemodialysis, peritoneal dialysis, or kidney transplantation)
11. Active immunosuppression therapy (including prednisone greater than or equal to 10 mg daily)
12. Kidney transplantation history
13. Solid organ transplantation history
14. Recent cardiovascular event (myocardial infarction, stroke, congestive heart failure (NYHA class ≥III or ejection fraction ≤30%) within 6 months or uncontrolled cardiac arrhythmias (e.g. ventricular arrhythmia, supraventricular tachycardia and bradyarrhythmia)
15. History of liver cirrhosis
16. Chronic obstructive pulmonary disease or asthma requiring daily medication
17. History of blood clotting disorder (thromboembolism; pulmonary embolism, deep venous thrombosis)
18. Pregnancy
19. Unwilling to use contraception for at least 2 months after MSC infusion if sexually active and able to become pregnant or father a child.
20. Active malignancy
21. Active infection (e.g. systemic or specific organ involvement such as pneumonia or osteomyelitis)
22. Recent COVID-19 infection within the last 3 months
23. History of hepatitis B or C (without cure), or HIV infection
24. History of allergic reaction to cellular products (ie. blood transfusions, platelets)
25. Active tobacco use
26. Illicit drug use and excessive alcohol use
27. Presence of psychosocial issues (e.g., uncontrolled mental illness, unpredictable childcare or eldercare responsibilities, irregular/ inflexible work schedule) that may interfere with the ability to complete all study procedures
28. Subjects anticipating prolonged travel or other physical restrictions that would prohibit return for scheduled study visits.
29. Inability to give informed consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose Arm 1; Subjects with chronic kidney disease will receive allogeneic bone marrow-derived mesenchymal stem cells (MSC) in two intravenous infusions of 100x10^6 cells at time zero and three months	Drug: Allogeneic adipose-derived mesenchymal stem cells (MSC); Two intravenous infusions delivered systemically through a peripheral IV(over 30 minutes to 2 hours) of 100x10^6 cells at day 0 and day 84; Drug: Allogeneic adipose-derived mesenchymal stem cells (MSC); Single intravenous infusion delivered systemically through a peripheral IV(over 30 minutes to 2 hours) of 200x10^6 cells at day 0
Experimental: Dose Arm 2; Subjects with chronic kidney disease will receive allogeneic bone marrow-derived mesenchymal stem cells (MSC) single intravenous infusion of 200x10^6 cells	Drug: Allogeneic adipose-derived mesenchymal stem cells (MSC); Two intravenous infusions delivered systemically through a peripheral IV(over 30 minutes to 2 hours) of 100x10^6 cells at day 0 and day 84; Drug: Allogeneic adipose-derived mesenchymal stem cells (MSC); Single intravenous infusion delivered systemically through a peripheral IV(over 30 minutes to 2 hours) of 200x10^6 cells at day 0

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events and/or serious adverse events	Number of adverse events and/or serious adverse events associated with mesenchymal stem cells intervention	15 months
Change in eGFR Value	Blood serum estimated glomerular filtration rate (eGFR) reported in milliliters per minute (mL/min)	6 months

Collaborators and Investigators

• Sponsor: LaTonya J. Hickson
• Investigators: Principal Investigator: LaTonya Hickson, MD, Mayo Clinic

Publications and helpful links

Helpful Links

• Mayo Clinic Clinical Trials

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2022
• Primary Completion (Actual): July 24, 2024
• Study Completion (Actual): July 24, 2024

Study Registration Dates

• First Submitted: May 2, 2022
• First Submitted That Met QC Criteria: May 2, 2022
• First Posted (Actual): May 5, 2022

Study Record Updates

• Last Update Posted (Actual): August 19, 2024
• Last Update Submitted That Met QC Criteria: August 15, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Urologic Diseases; Disease Attributes; Renal Insufficiency; Chronic Disease; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Renal Insufficiency, Chronic
• Other Study ID Numbers: 21-011822

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No