Overview
The goal of this clinical trial is to Evaluate the Safety and Preliminary Efficacy of Human Umbilical Cord Mesenchymal Stem Cell-Derived Exosomes in the Treatment of Adult Type 2 Diabetes Mellitus.
Description
A two-stage, progressive mixed design will be adopted to balance ethical considerations and scientific rigor.
Stage 1 (Open-Label, Before-and-After Study) will employ a sequential, open-label dose-escalation design:
A total of 18 patients will be enrolled, all receiving a 2-month course (once weekly, 8 doses total) of intravenous exosome infusion therapy. This study uses a sequential dose-escalation design with three dose cohorts: low-dose (1×10¹¹ particles), medium-dose (3×10¹¹ particles), and high-dose (9×10¹¹ particles). Dose escalation will strictly adhere to the following procedure:
Sequential Progression: The study for the next dose cohort can only commence after all subjects in the previous dose cohort have completed the required safety observation period (i.e., the 5-week follow-up post-last dose) and the safety data has been reviewed.
Stage 2 (Randomized, Double-Blind, Active-Comparator Parallel Study):
Provided no major safety issues are identified in the first stage, the second stage will commence. This stage plans to enroll 48 patients, randomized 2:1 to either the exosome treatment group (n=32) or the active-comparator control group (n=16).
Follow-up Plan: Multiple visits are scheduled, including a baseline period, treatment period (after each dose), end of treatment (Week 8/Month 2), and post-treatment follow-up periods (Week 12, Month 3, Month 6, Month 12), to systematically evaluate efficacy and safety.
Eligibility
Inclusion Criteria:
- Age 18-65 years, diagnosed with T2DM for ≥5 years (\<20 years).
- Regular diet and exercise control combined with the following intensive treatment regimens, with screening HbA1c remaining between 7.5% and 9.0% (FBG \<13.9mmol/L):Stable dose of insulin (basal or premixed) (\<1.5u/kg·d) combined with ≥1 oral antidiabetic drug (OAD) (e.g., Metformin, SGLT2i) for ≥3 months; or Insulin combined with a GLP-1RA (maximum tolerated dose, ≤1mg Qw); or GLP-1RA (maximum tolerated dose, ≤1mg Qw) combined with ≥1 OAD for ≥3 months; or Stable dose of ≥3 OADs (must include Metformin) for ≥3 months.
- Fasting C-peptide ≥1.0 ng/mL.
- Glutamic acid decarboxylase (GAD) antibody and Islet cell antibody (IAA) negative.
- Body Mass Index (BMI) 18.5-35 kg/m ².
- Subjects voluntarily participate in the study and sign the informed consent form.
- Female subjects of childbearing potential and non-sterilized male subjects must agree to use highly effective contraceptive methods during the study period and for 1 year following the final infusion.
Exclusion Criteria:
- Type 1 diabetes or other specific types of diabetes.
- Occurrence of severe hypoglycemia or diabetic ketoacidosis within the past 6 months.
- Severe cardiovascular/cerebrovascular diseases, hepatic or renal insufficiency (e.g., eGFR \<30 mL/min·1.73m²).
- Active malignancy, coagulation disorders, immune system diseases.
- Pregnant or lactating women.
- Individuals with allergic constitution.
- Exclusion of subjects currently participating in other clinical trials.
- Subjects deemed unsuitable for participation by the investigator.
