Autologous Islet Transplantation for Diabetes

Official title

Exploratory Clinical Study of Adult Pancreatic Progenitor-derived Islet Autologous Transplantation in the Treatment of Diabetes

Overview

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.

Interventions

• Biological Autologous islet transplantation
  1. EUS-FNB or surgical procurement of pancreatic tissue 2. In vitro culture of adult pancreatic progenitor 3. In vitroinduction of islets 4. islet transplantation beneath the anterior rectus sheath 5. Post-transplant follow-up

Primary outcome measures

• Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 [Time frame: Within one year after transplant]
• Hypoglycemia incidence rate [Time frame: Within one year after transplant]

Secondary outcome measures (6)

• Changes in glycosylated hemoglobin (HbA1c) from baseline at 3 months, 6 months, 9 months, and 1 year after transplantation [Time frame: 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 [Time frame: 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 [Time frame: Within one year after transplant]
• Changes in insulin at 3 months, 6 months, 9 months, and 1 year post-transplantation compared to baseline [Time frame: Within one year after transplant]
• Changes in C-peptide at 3 months, 6 months, 9 months, and 1 year post-transplantation compared to baseline [Time frame: 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 [Time frame: Within one year after transplant]

Eligibility criteria

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.

II. Exclusion Criteria:

• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Zhongshan Hospital — Shanghai

Identifiers

NCT: NCT07118475 · B2025-257

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗