An Exploratory Clinical Study Assessing the Safety and Preliminary Efficacy of Human Umbilical Cord Mesenchymal Stem Cell-Derived Exosomes in the Treatment of Adult Type 2 Diabetes Mellitus
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 66
- 试验地点
- 1
- 主要终点
- Change in Glycated Hemoglobin (HbA1c)
研究概览
简要总结
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.
详细描述
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):
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Masking Description
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
结局指标
主要结局
Change in Glycated Hemoglobin (HbA1c)
时间窗: Baseline, Week 8
The primary efficacy endpoint is the change in glycated hemoglobin (HbA1c) from baseline to Week 8. In the randomized comparative stage, between-group differences between the investigational intervention group and the control group will also be evaluated. Unit of Measure: Percentage (%) Interpretation: Reflects long-term glycemic control and overall metabolic efficacy of the intervention.
次要结局
- Glycated Hemoglobin (HbA1c) Response Rate(Week 24, Week 52)
- Pancreatic Islet Function: Insulin (INS)(Baseline, Week 4, Week 8，Week 12, Week 24, Week 52)
- Pancreatic Islet Function: C-peptide(Baseline, Week 4, Week 8, Week 12, Week 24, Week 52)
- Changes in Blood Glucose during MMTT(Baseline, Week 8, Week 52)
- Anthropometric and Metabolic Parameters(Baseline, Week 2, Week 4, Week 6, Week 8, Week 12, Week 24, Week 52)
- Soluble Adhesion Molecule (sICAM-1)(Baseline, Week 4, Week 8, Week 12, Week 24, Week 52)
- Ophthalmologic Assessment(Baseline, Week 24)
- Change in Central Obesity: Waist-to-Hip Ratio (WHR)(Baseline, Week 4, Week 8, Week 12, Week 24, Week 52)
- Body fat percentage (%)(Baseline, Week 8, Week 24, Week 52)
- C-Reactive Protein (CRP)(Baseline, Week 4, Week 8, Week 12, Week 24, Week 52)
- Time in Range (TIR, 3.9-10.0 mmol/L)(baseline to week 8)
- Mean glucose level(baseline to week 8)
- Coefficient of variation (CV%)(Baseline to week 8)
- Inflammatory Biomarkers：Interleukin-4 (IL-4)(Baseline, Week 4, Week 8, Week 12, Week 24, Week 52)
- Inflammatory Biomarkers：Interleukin-6（ IL-6）(Baseline, Week 4, Week 8, Week 12, Week 24, Week 52)
- Inflammatory Biomarkers：Interleukin- 1β (IL-1β)(Baseline, Week 4, Week 8, Week 12, Week 24, Week 52)
- Inflammatory Biomarkers：Interleukin-10 (IL-10)(Baseline, Week 4, Week 8, Week 12, Week 24, Week 52)
- Inflammatory Biomarkers：Interleukin-8 (IL-8)(Baseline, Week 4, Week 8, Week 12, Week 24, Week 52)
- Inflammatory Biomarkers：Interleukin-2 (IL-2)(Baseline, Week 4, Week 8, Week 12, Week 24, Week 52)
- Inflammatory Biomarkers：Tumor Necrosis Factor-alpha (TNF-α)(Baseline, Week 4, Week 8, Week 12, Week 24, Week 52)
- Inflammatory Biomarkers：Interferon-gamma (IFN-γ)(Baseline, Week 4, Week 8, Week 12, Week 24, Week 52)
- Inflammatory Biomarkers：Interferon-alpha (IFN-α)(Baseline, Week 4, Week 8, Week 12, Week 24, Week 52)
- Inflammatory Biomarkers： Interleukin-17A（IL-17A）(Baseline, Week 4, Week 8, Week 12, Week 24, Week 52)
- Inflammatory Biomarkers：Interleukin-12p70 (IL-12p70)(Baseline, Week 4, Week 8, Week 12, Week 24, Week 52)
- Inflammatory Biomarkers：Interleukin-5 (IL-5)(Baseline, Week 4, Week 8, Week 12, Week 24, Week 52)
- High-Density Lipoprotein Cholesterol (HDL-C)(Baseline, Week 4, Week 8, Week 12, Week 24, Week 52)
- Low-Density Lipoprotein Cholesterol (LDL-C)(Baseline, Week 4, Week 8, Week 12, Week 24, Week 52)
- Total Cholesterol (TC)(Baseline, Week 4, Week 8, Week 12, Week 24, Week 52)
- Triglycerides (TG)(Baseline, Week 4, Week 8, Week 12, Week 24, Week 52)
- Hepatic Fibrosis (LSM)(Baseline, week 24)
- Hepatic Steatosis (CAP)(Baseline, week 24)
- Carotid Atherosclerosis Assessment: Plaque Size(Baseline, Week 24,)
- Carotid Atherosclerosis Assessment: Comparison of bilateral Carotid Intima-Media Thickness (CIMT)(Baseline, Week 24,)
- Urine Albumin-to-Creatinine Ratio (UACR)(Baseline, Week 8, Week 24)
- Changes in Insulin Secretion during MMTT(Baseline, Week 8, Week 52)
- Changes in C-peptide Levels during MMTT(Baseline, Week 8, Week 52)
- Change in Homeostatic Model Assessment for Insulin Resistance (HOMA-IR)(Baseline, Week 8, Week 52)
- Change in Homeostatic Model Assessment for β-cell Function (HOMA-β)(Baseline, Week 8, Week 52)
- Diabetes Specific Quality of Life (DSQL)(Baseline, Week 8, Week 52)