Diabetic nephropathy (DN) is a chronic kidney disease caused by diabetes. It is one of the most common and most serious microvascular complications of diabetes. Current treatment options for DN are limited. Mesenchymal stem cells (MSCs) are considered one of the promising treatments for DN. This study aims to evaluate the safety, tolerability, and preliminary efficacy of human umbilical cord mesenchymal stem cell injection in patients with type 2 DN.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
49
Participants will receive intravenous infusions of allogeneic human umbilical cord MSCs in addition to standard treatment. Phase I will evaluate three dose levels (0.5×10\^6/kg, 1.0×10\^6/kg and 2.0×10\^6/kg). Phase IIa will use dose level 1.0×10\^6/kg, subject to adjustment based on Phase I results. Each 6-week treatment cycle will include three infusions administered at 2-week intervals, for a total of three treatment cycles.
The First People's Hospital of Changzhou
Changzhou, Jiangsu, China
Phase I: Incidence and severity of adverse events (AEs) and serious adverse events (SAEs), and clinically significant abnormalities in vital signs, electrocardiogram (ECG), and laboratory tests
AEs and SAEs will be graded according to the NCI-CTCAE version 5.0. Changes in vital signs, ECG, and routine laboratory tests will be monitored throughout the study. The recommended Phase II dose (RP2D) will be determined from Phase I results.
Time frame: From enrollment to 6 months after the end of treatment
Phase IIa: Proportion of participants achieving marked response or moderate response to human umbilical cord mesenchymal stem cell injection for type 2 DN
Marked response is defined as significant improvement in clinical symptoms together with complete remission of proteinuria \[urinary albumin-to-creatinine ratio (UACR) \<30 mg/g\], or significant improvement in estimated glomerular filtration rate (eGFR) (serum creatinine reduced by ≥20%). Moderate response is defined as partial alleviation of clinical symptoms and partial remission of proteinuria without complete resolution; either the UACR or 24-hour urinary protein level decreases by ≥50%, or eGFR improves (serum creatinine reduced by ≥10%). No response is defined as no improvement in clinical symptoms and no remission of proteinuria. The reduction of either UACR or 24-hour urinary protein level is less than 50%, and there is no improvement in eGFR (serum creatinine reduced by \<10%).
Time frame: From enrollment to 6 months after the end of treatment
Phase I: Proportion of participants achieving marked response or moderate response to human umbilical cord mesenchymal stem cell injection for type 2 DN
Marked response is defined as significant improvement in clinical symptoms together with complete remission of proteinuria \[UACR\<30 mg/g\], or significant improvement in eGFR (serum creatinine reduced by ≥20%). Moderate response is defined as partial alleviation of clinical symptoms and partial remission of proteinuria without complete resolution; either the UACR or 24-hour urinary protein level decreases by ≥50%, or eGFR improves (serum creatinine reduced by ≥10%). No response is defined as no improvement in clinical symptoms and no remission of proteinuria. The reduction of either UACR or 24-hour urinary protein level is less than 50%, and there is no improvement in eGFR (serum creatinine reduced by \<10%).
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Time frame: From enrollment to 6 months after the end of treatment
Phase IIa: Incidence and severity of AEs and serious SAEs and clinically significant abnormalities in vital signs, ECG, and laboratory tests
AEs and SAEs will be graded according to the NCI-CTCAE version 5.0. Changes in vital signs, ECG, and routine laboratory tests will be monitored throughout the study.
Time frame: From enrollment to 6 months after the end of treatment
Renal function
Changes in serum creatinine, blood urea nitrogen, eGFR
Time frame: From enrollment to 6 months after the end of treatment
24-Hour urinary protein quantification
Change in 24-hour urinary protein quantification
Time frame: From enrollment to 6 months after the end of treatment
UACR
Change in UACR
Time frame: From enrollment to 6 months after the end of treatment
Glycated hemoglobin (HbA1c)
Change in HbA1c
Time frame: From enrollment to 6 months after the end of treatment
Fasting blood glucose
Change in fasting blood glucose
Time frame: From enrollment to 6 months after the end of treatment
2-Hour postprandial blood glucose
Change in 2-hour postprandial blood glucose
Time frame: From enrollment to 6 months after the end of treatment
Fasting insulin
Change in fasting insulin
Time frame: From enrollment to 6 months after the end of treatment
Fasting C-Peptide
Change in fasting C-peptide
Time frame: From enrollment to 6 months after the end of treatment
Fasting lipid profile
Changes in triglycerides, total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol
Time frame: From enrollment to 6 months after the end of treatment
Serum albumin
Change in serum albumin
Time frame: From enrollment to 6 months after the end of treatment
Oral glucose tolerance test (OGTT)
Changes in OGTT measurements collected after overnight fasting
Time frame: From enrollment to 6 months after the end of treatment
C-peptide release test
Changes in C-peptide release test measurements collected after overnight fasting
Time frame: From enrollment to 6 months after the end of treatment
Fasting body weight
Change in fasting body weight
Time frame: From enrollment to 6 months after the end of treatment
Body mass index
Body mass index is calculated as weight (kg) divided by height squared (m²), with results in kg/m².
Time frame: From enrollment to 6 months after the end of treatment
Waist circumference
Change in waist circumference
Time frame: From enrollment to 6 months after the end of treatment
Hip Circumference
Change in hip circumference
Time frame: From enrollment to 6 months after the end of treatment
Waist-to-hip ratio
Waist-to-hip ratio is calculated as waist circumference divided by hip circumference, with results as a dimensionless value.
Time frame: From enrollment to 6 months after the end of treatment