Human Umbilical Cord Mesenchymal Stem Cell Infusion for Type 2 Diabetic Nephropathy

This is a Phase I/IIa clinical trial evaluating the safety, tolerability, and preliminary efficacy of human umbilical cord mesenchymal stem cell injection in patients with type 2 DN. Phase I is a single-center, prospective, open-label, self-controlled study to evaluate the safety and tolerability of MSCs and determine the recommended Phase II dose (RP2D). Phase IIa is a randomized, open-label, standard treatment-controlled study to preliminarily evaluate efficacy.

Inclusion criteria

• Aged 18 to 80 years, with no gender and ethnicity restrictions.
• Patients who meet the diagnostic criteria for type 2 diabetes mellitus (T2DM) as defined by the Chinese Guideline for the Prevention and Treatment of Type 2 Diabetes Mellitus (2020 Edition), with:

• Baseline serum C-peptide concentrations ranging from 0.3 to 3.0 ng/mL;
• Stable antihyperglycemic and antihypertensive medication regimen for at least 3 months prior to screening, defined as dosage adjustment less than 25%.
• Urinary albumin-to-creatinine ratio (UACR) ≥ 30 and ≤ 5000 mg/g together with estimated glomerular filtration rate (eGFR) ≥ 30 and < 90 mL/min/1.73 m².
• Patients are required to have renal biopsy-proven DN glomerulopathy with Tervaert Class IIa to Class III glomerular lesions.
• Patients voluntarily agree to participate and provide written informed consent after full disclosure of the study's purpose, procedures, nature, and potential adverse reactions.

Exclusion criteria

• Other non-T2DM, such as type 1 diabetes.
• Individuals allergic to MSCs or their preservation solution.
• Individuals with any of the following conditions during screening:

• History of acute diabetic complications within the past 6 months, including diabetic ketoacidosis, hyperglycemic hyperosmolar state, or lactic acidosis;
• Unstable disease status or severe diabetic complications within the past 6 months, such as proliferative diabetic retinopathy or macular edema, severe diabetic neuropathy, intermittent claudication, active diabetic foot lesions;
• History of three or more Level 3 hypoglycemic events within the past 6 months, as defined by the Guidelines for the Management of Type 2 Diabetes in China (2020 Edition);
• History of any of the following cardiac conditions within the past 6 months: decompensated heart failure (New York Heart Association Class III-IV); unstable angina, myocardial infarction, coronary artery bypass grafting, or coronary stent implantation; severe arrhythmias requiring treatment, including second-degree or third-degree atrioventricular block, long QT syndrome, or QTc interval prolongation ≥ 500 ms, and deemed by the investigator to render the subject unsuitable for study participation;
• History of hemorrhagic or ischemic stroke within the past 6 months deemed by the investigator to render the subject unsuitable for study participation;
• History of other severe endocrine disorders affecting glucose metabolism, such as multiple endocrine neoplasia, acromegaly, and Cushing's syndrome, deemed by the investigator to render the subject unsuitable for study participation;
• History of severe digestive system diseases, nutritional and metabolic disorders, or rheumatologic diseases, deemed by the investigator to render the subject unsuitable for study participation;
• Concurrent malignancy or history of malignancy (except malignancies with at least 5 years of disease-free survival);
• Severe psychiatric disorder or speech impairment, or the subject is unwilling or unable to fully understand and comply with study requirements;
• Severe infection or major surgery within the past 6 months, deemed by the investigator to render the subject unsuitable for study participation;
• Acquired Immunodeficiency Syndrome, active hepatitis B, hepatitis C infection, or other acute or chronic infectious diseases;
• Poorly controlled blood pressure, defined as a systolic blood pressure > 180mmHg and/or diastolic blood pressure > 110mmHg.
• Laboratory test results meet the following criteria:

• Alanine aminotransferase or aspartate aminotransferase ≥ 2.5 times the upper limit of normal (ULN);
• Total bilirubin ≥ 2.0 times ULN;
• Currently suffering from severe renal disease, or eGFR (CKD-EPI2012Scr-CysC) < 30 mL/min/1.73 m²;
• Fasting triglycerides > 5.6 mmol/L;
• Serum amylase or serum lipase ≥ 1.5 times ULN;
• Hemoglobin < 10.0 g/dL (100 g/L), serum albumin < 30 g/L;
• Glycosylated hemoglobin ≥ 10%.
• History of long-term systemic corticosteroid administration (consecutive or cumulative ≥ 7 days) within 1 month prior to screening (including but not limited to intravenous administration, oral administration, or intramuscular injection).
• Renal replacement therapy within 3 months prior to screening, current ongoing, or planned initiation within the next 3 months (including hemodialysis, peritoneal dialysis, continuous renal replacement therapy).
• Participation in other drug or device clinical trials within 3 months prior to screening.
• Previous use of other stem cell treatments.
• Use of immunosuppressants, tripterygium glycosides, eplerenone, spironolactone, or similar agents within 3 months prior to screening.
• Pregnancy, lactation, or intention to become pregnant during the study period.
• Any other condition that, in the investigator's judgment, would make the subject unsuitable for the study.
• Renal biopsy revealing DN with coexisting non-DN pathology.