Exploratory Clinical Study of Adult Pancreatic Progenitor-derived Islet Autologous Transplantation in the Treatment of Diabetes
试验速览
- 阶段
- 1 期
- 状态
- Enrolling By Invitation
- 发起方
- 入组人数
- 24
- 试验地点
- 2
- 主要终点
- Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
研究概览
简要总结
This study aims to conduct an exploratory clinical trial recruiting insulin-dependent diabetic patients who meet the criteria for islet transplantation. Pancreatic tissue will be obtained via endoscopic ultrasound-guided fine-needle aspiration biopsy, and adult pancreatic progenitor cells (APP) will be expanded in vitro and differentiated into islet-like cells. After quality assessment, these cells will be transplanted via injection beneath the anterior rectus sheath.
Following autologous transplantation of APP-derived islets, the transplanted islets are expected to survive at the implantation site, stably secrete insulin, and thereby reduce or potentially eliminate the need for exogenous insulin. Glycated hemoglobin (HbA1c) levels are anticipated to decrease, with a significant reduction in the risk of severe hypoglycemic episodes, and no transplant-related adverse events are expected.
As this is an exploratory clinical study, participants may not benefit from APP islet transplantation and may face risks or adverse events associated with the procedure. However, the findings of this research may advance more scientific and effective treatment strategies for diabetes. The successful completion of this study could provide a feasible and scalable approach to functionally curing diabetes, effectively reducing disability and mortality rates among diabetic patients, improving their quality of life, and generating substantial health, economic, and social benefits.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •I. Eligibility Criteria:
- •Age of 18-75 years (inclusive of 18 and 75) on the day of signing the informed consent form, without gender restriction;
- •Type 2 diabetes patients who meet the diagnostic criteria of the "Chinese Diabetes Prevention and Control Guidelines (2024 Edition)";
- •Dependent on exogenous insulin therapy;
- •Compensatory failure or exhaustion of pancreatic function: ① Fasting serum C-peptide ≤ 1.0 ng/ml in the absence of hypoglycemia (blood glucose > 3.9 mmol/l); ② The average difference ≤ 1.0 ng/ml in serum C-peptide levels at 2, 4, and 6 minutes after arginine stimulation (intravenous injection of 5g arginine) compared to baseline .
- •Ability to participate in intensive glucose management with good compliance;
- •Mentally stable and able to adhere to the clinical study protocol;
- •Possessing full civil capacity and the ability to independently complete a written informed consent form.
排除标准
- •Inability to tolerate endoscopic ultrasound-guided pancreatic puncture biopsy due to various reasons;
- •Inability to tolerate subcostal sheath injection due to various reasons;
- •Body mass index (BMI) > 30 kg/m²;
- •Un-treated proliferative diabetic retinopathy;
- •History of infectious diseases such as hepatitis B, hepatitis C, HIV, and tuberculosis, or presence of active bacterial, fungal, or viral infections (excluding mild localized skin infections);
- •Severe heart disease, meeting any of the following criteria: history of recent myocardial infarction (within the past 6 months), myocardial ischemia identified in myocardial function assessment within the past year, or left ventricular ejection fraction <30%;
- •Blood pressure: systolic blood pressure >160 mmHg or diastolic blood pressure >100 mmHg;
- •Liver function indicators: Serum aspartate aminotransferase (AST) and serum alanine aminotransferase (ALT) are more than twice the upper limit of normal values;
- •Glomerular filtration rate (GFR) < 60 ml/min/1.73m²;
- •History of invasive aspergillosis, histoplasmosis, or coccidioidomycosis within the past year;
- •Laboratory findings showing hemoglobin (Hb) below 90 g/L, or lymphopenia (0.5×10⁹/L), neutropenia (<1.0×10⁹/L), or thrombocytopenia (<75×10⁹/L);
- •Patients with any coagulation disorder or other disease requiring long-term anticoagulant therapy, or those with an International Normalized Ratio (INR) > 1.5;
- •Female patients: positive pregnancy test, breastfeeding, or unwilling to use effective contraception during the study; male patients: planning to father a child during the study or unwilling to use effective contraception;
- •History of prior tumor (excluding completely resected squamous cell carcinoma and cutaneous basal cell carcinoma);
- •History of smoking, alcohol abuse, or drug abuse;
- •Severe gastrointestinal dysfunction, gastrointestinal immune diseases, peptic ulcers, and other conditions that may interfere with oral drug absorption;
- •Have severe mental and psychological disorders;
- •Have participated in other clinical trials in the past 3 months;
- •History of receiving attenuated live vaccines within 2 months of registration;
- •Researchers believe that other reasons make the participant unsuitable for this clinical trial.
研究组 & 干预措施
Autologous islet transplantation
干预措施: Autologous islet transplantation (Biological)
结局指标
主要结局
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
时间窗: Within one year after transplant
Adverse events will be coded according to the MedDRA dictionary, and AE will be graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 of the National Cancer Institute.
Hypoglycemia incidence rate
时间窗: Within one year after transplant
Hypoglycemia can be divided into three levels based on blood sugar levels, physical changes, and state of consciousness.
次要结局
- Changes in glycosylated hemoglobin (HbA1c) from baseline at 3 months, 6 months, 9 months, and 1 year after transplantation(Within one year after transplant)
- Changes in time in range (TIR) at 3 months, 6 months, 9 months, and 1 year post-transplantation compared to baseline(Within one year after transplant)
- Changes in fasting plasma glucose at 3 months, 6 months, 9 months, and 1 year post-transplantation compared to baseline(Within one year after transplant)
- Changes in insulin at 3 months, 6 months, 9 months, and 1 year post-transplantation compared to baseline(Within one year after transplant)
- Changes in C-peptide at 3 months, 6 months, 9 months, and 1 year post-transplantation compared to baseline(Within one year after transplant)
- Changes in exogenous insulin dosage at 3 months, 6 months, 9 months, and 1 year post-transplantation compared to baseline(Within one year after transplant)