T3c Diabetes
Conditions
Interventions
HLA-matched pancreatic endocrine organoids transplantation:Islet cells are isolated from resected pancreatic tissue obtained from patients undergoing surgery, followed by ex vivo expansion and culture
Sponsors
Zhongshan Hospital Fudan University
Eligibility
Sex/Gender
All
Age
18 Years to 70 Years
Inclusion criteria
Inclusion criteria: 1. Voluntarily signs the informed consent form and agrees to comply with the study treatment protocol and visit schedule; 2. Aged between 18 and 70 years (inclusive) on the day of signing the informed consent form, with no gender restriction; 3. Has undergone total pancreatectomy, with baseline C-peptide levels below the lower limit of the normal range; 4. Exhibits hyperglycemia following pancreatic surgery and meets the diagnostic criteria for type 3c diabetes mellitus (T3cDM); 5. Has a mixed-meal stimulated 120-minute C-peptide level of <0.3 ng/mL; 6. Male participants who are sexually active and neither surgically sterilized nor have partners incapable of childbearing must agree to use effective contraception and refrain from sperm donation throughout the study period and for at least 6 months after study completion; female participants of childbearing potential must agree to use effective contraception throughout the study period and for at least 6 months after study completion.
Exclusion criteria
Exclusion criteria: 1. Previous history of pancreatic or islet transplantation; 2. Uncontrolled hypertension, defined as systolic blood pressure (SBP) >160 mmHg and/or diastolic blood pressure (DBP) >100 mmHg despite stable antihypertensive therapy (for at least 4 weeks); 3. Known hemoglobinopathies, moderate to severe anemia, or other disorders known to interfere with HbA1c measurement (e.g., sickle cell disease); 4. Impaired liver or renal function at screening, defined as: aspartate aminotransferase (AST) >3× the upper limit of normal (ULN), alanine aminotransferase (ALT) >3× ULN, total bilirubin (TBL) >2× ULN (except for Gilbert's syndrome); creatinine clearance =104 copies/mL or >=2000 IU/mL. Participants with HBsAg positivity and HBV DNA =10³ IU/mL; Positive for human immunodeficiency virus (HIV) antibody; Active syphilis infection (participants with adequately treated syphilis may be eligible); Positive cytomegalovirus (CMV) DNA; Positive nucleic acid test for COVID-19;** 6. History of coagulation disorders or requiring long-term anticoagulation therapy (e.g., warfarin) (low-dose aspirin use is permitted), or international normalized ratio (INR) >1.5; 7. History of pancreatic cancer, intraductal papillary mucinous neoplasm (IPMN) of the pancreas, end-stage pulmonary disease, or liver cirrhosis; 8. Other clinically significant laboratory abnormalities as determined by the investigator.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| A >=50% reduction in daily insulin dose compared to baseline (pre-transplantation) by 52 weeks post-transplantation;HbA1c < 7.0% by 52 weeks post-transplantation;No episodes of severe hypoglycemia between weeks 12 and 52 post-transplantation; | — |
Secondary
| Measure | Time frame |
|---|---|
| Proportion of subjects with HbA1c 0.3 ng/ml following a mixed meal tolerance test at weeks 12, 26, and 52 post-transplantation;Time-in-range (TIR) and mean amplitude of glycemic excursions (MAGE) at weeks 12, 26, and 52 posttransplantation;Cumulative Hypoglycemic episodes at weeks 12, 26, and 52 post-transplantation; Other adverse events (AEs), serious adverse events (SAEs), and adverse events of special interest (AESIs);Quality of life scores at baseline, and weeks 52, assessed via validated questionnaires; | — |
Countries
China
Contacts
Public ContactLiang Liu
Zhongshan Hospital Fudan University
Outcome results
None listed