Clinical trial NCT06415643: The Use of Islet Organoids in the Treatment of Pancreatic Surgery-related Diabetes
Official title: The Use of Islet Organoids in the Treatment of Pancreatic Surgery-related Diabetes
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: T3c Diabetes
Lead sponsor: Zhejiang University
Sponsor class: OTHER
Collaborators: name: Newislet Biotechnology (Shanghai) Ltd.
First posted: 2024-05-16
Enrollment: 5
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this clinical trial is to verify the safety and effectiveness of autologous islet organoids transplantation after in vitro expansion for the treatment of pancreatogenic diabetes.

Detailed description: The purpose of this clinical trial is to verify the safety and effectiveness of autologous islet transplantation after in vitro expansion in the forms of functional islet organoids, for the treatment of pancreatogenic diabetes in participants who have undergone pancreatic resection through a single-center single-arm study. The investigators aim to establish the entire operational process of isolating expanding and transplanting islets from the pancreas removed from the participants and managing postoperative care. The investigators hope to accumulate clinical experience in treating pancreatogenic diabetes with transplanted autologous islet cell clusters expanded in vitro establish standard and regulated medical operations and gather materials for future applications of this treatment method in clinical practice.

Eligibility criteria: Inclusion Criteria:

1. Voluntarily sign the informed consent form and adhere to the trial treatment plan and visit schedule.
2. When signing the informed consent form, the age should be between 18-70 years old, with no gender restrictions.
3. Good overall health condition: no damage to important organs such as heart, lungs, liver, kidneys, no serious or uncontrolled infections, and no history of severe mental disorders.
4. Meets the diagnosis of pancreatic tumor, chronic pancreatitis (diffuse pancreatic duct stones, refractory pain, associated with high risk of pancreatic cancer), pancreatic trauma, postoperative pancreatic fistula with class C, pancreatic cystic fibrosis, has indications for total or subtotal pancreatectomy, and no chronic organ failure.
5. Clinical examinations must meet the following criteria: Normal glycated hemoglobin (HbA1c) measurement.
6. Normal alanine aminotransferase (ALT) measurement, or abnormal but clinically insignificant
7. negative for Hepatitis A virus antibody (HAV antibody), Hepatitis B virus surface antigen (HBsAg) and e antigen, Hepatitis C virus antibody (HCV antibody), Human Immunodeficiency Virus antibody (HIV-1 and HIV-2 antibody), Syphilis antibody, Epstein-Barr virus antibody (EBV antibody), Cytomegalovirus (CMV-DNA), B19 virus nucleic acid, Human T-lymphotropic virus antibody.
8. Male participants who are sexually active and have not undergone surgical sterilization or whose partners are capable of childbearing, agree to take effective contraceptive measures for the entire trial period and at least 6 months after the end of the study, and not to donate sperm. Female participants capable of childbearing agree to take effective contraceptive measures for the entire study period and at least 6 months after the end of the study.
9. Post-pancreatic surgery blood sugar increase, meeting the diagnostic criteria for diabetes (World Health Organization 2019 edition).
10. C-peptide level \<0.3 ng/mL 120 minutes after mixed meal stimulation before pancreatic islet transplantation.

Exclusion Criteria:

1. The investigator considers the following diseases to be clinically significant: a history of diabetes, or preoperative hyperglycemia, meeting the diagnosis of diabetes.
2. Undergone previous pancreatic or islet transplantation
3. Uncontrolled hypertension, such as systolic blood pressure (SBP) \>160 mmHg and/or diastolic blood pressure (DBP) \>100 mmHg after treatment with a stable dose (at least 4 weeks) of antihypertensive drugs.
4. Fatty hepatitis, portal vein thrombosis, portal hypertension, anterolateral pancreatic jejunostomy, or visceral hyperalgesia.Impaired liver and kidney function at screening (reference to the normal range of laboratory tests in the research center): aspartate aminotransferase (AST) \>3 times the upper limit of normal (ULN), alanine aminotransferase (ALT) \>3 times ULN, total bilirubin level (TBL) \>2 times ULN (excluding Gilbert's syndrome). Creatinine clearance \<45 mL/min (calculated by Cockcroft-Gault formula)
5. Women in pregnancy, less than 6 months after miscarriage, less than 1 year after delivery and lactation.
6. History of infectious diseases including but not limited to hepatitis A, hepatitis B, hepatitis C, HIV and syphilis
7. Presence of known hemoglobin-related diseases, anemia (moderate to severe) or other known hemoglobin diseases that interfere with HbA1c measurement (such as sickle cell disease). Presence of massive albuminuria (urinary protein excretion rate \>300 mg/g) or past medical history.
8. Presence of severe heart disease or cardiovascular disease within 6 months before screening, including: stroke, decompensated heart failure (NYHA class III or IV), myocardial infarction, unstable angina, those who have undergone coronary artery bypass grafting.
9. History of coagulation disorders or need for long-term anticoagulation treatment (such as warfarin) (low-dose aspirin treatment is allowed) or INR\>1.5
10. Treatment (local, intra-articular, intraocular, or inhaled formulations) for any other factors or diseases, other than the above reasons, that the researcher deems unsuitable for participation in this clinical study.

Primary outcomes:
measure: C-peptide secretion
timeFrame: before transplantation and 1 year after transplantation
Secondary outcomes:
measure: HbA1c level
timeFrame: before transplantation and 1 year after transplantation
measure: Mean Amplitude of Glycemic Excursion (MAGE)
timeFrame: 12 weeks and 52 weeks post transplantation
measure: Ryan Hypoglycemia event
timeFrame: baseline and 52 weeks post transplantation
measure: Reduced Insulin usage
timeFrame: 12 weeks and 52 weeks post transplantation
Other outcomes:
Locations:
city: Hangzhou
country: China
facility: Zhejiang University Second Affiliated Hospital
state: Zhejiang
Study officials:
affiliation: Zhejiang University Second Affiliated Hospital
name: Sheng Yan, PhD, MD
role: PRINCIPAL_INVESTIGATOR
References: