The Use of Islet Organoids in the Treatment of Pancreatic Surgery-related Diabetes

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.

Study Overview

• Status: Recruiting
• Conditions: T3c Diabetes
• Intervention / Treatment: Other: Islet organoids transplantation

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.

• Study Type: Interventional
• Enrollment (Estimated): 5
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Xi Ma, MD; Phone Number: 86-18768117002; Email: xima@zju.edu.cn
• Study Contact Backup: Name: Qing Cissy Yu, PhD; Phone Number: 86-13916205952; Email: qing.yu@newislet.com

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China
      • Recruiting
      • Zhejiang University Second Affiliated Hospital
      • Contact: Xi Ma, MD; Phone Number: 86-18768117002; Email: xima@zju.edu.cn
      • Principal Investigator: Sheng Yan, PhD,MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Transplantation group; transplantation group	Other: Islet organoids transplantation; autologous transplantation of ex vivo expanded islet organoids.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
C-peptide secretion	C-peptide detection assay	before transplantation and 1 year after transplantation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
HbA1c level	HbA1c detection assay	before transplantation and 1 year after transplantation
Mean Amplitude of Glycemic Excursion (MAGE)	Glucose measurement	12 weeks and 52 weeks post transplantation
Ryan Hypoglycemia event	recorded events of unaware severe hypoglycemia (glucose level below 3 mmol/L)	baseline and 52 weeks post transplantation
Reduced Insulin usage	Reduced insulin usage of over 50% compared with prior to treatment	12 weeks and 52 weeks post transplantation

Collaborators and Investigators

• Sponsor: Zhejiang University
• Collaborators: Newislet Biotechnology (Shanghai) Ltd.
• Investigators: Principal Investigator: Sheng Yan, PhD, MD, Zhejiang University Second Affiliated Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): August 10, 2024
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: May 9, 2024
• First Submitted That Met QC Criteria: May 14, 2024
• First Posted (Actual): May 16, 2024

Study Record Updates

• Last Update Posted (Actual): July 30, 2024
• Last Update Submitted That Met QC Criteria: July 28, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus
• Other Study ID Numbers: YD-ZE-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No