Clinical Study on the Safety and Efficacy of Immunophenotyped Pancreatic Endocrine Organoid Bank in Treating Patients With T3c Diabetes

Fudan University

Status and phase: Active, not recruiting; Early Phase 1

Conditions: Diabetes Mellitus

Treatments: Procedure: HLA-matched pancreatic endocrine organoids transplantation

Study type: Interventional

Funder types: Other

Identifiers

NCT06991829

ZSPAC-10

Details and patient eligibility

About

Islet cells are isolated from resected pancreatic tissue obtained from patients undergoing surgery, followed by ex vivo expansion and culture. Subsequent procedures include HLA typing, functional assessment of organoid-like structures, and biobanking. After matching for HLA, the cells are administered into patients with type 3c diabetes mellitus (T3cDM) via ultrasound-guided percutaneous transhepatic portal vein catheterization. A 52-week follow-up is conducted to evaluate the safety of the cell therapy and its clinical efficacy in glycemic control.

Enrollment: 29 estimated patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Aged ≥18 and ≤70 years at the time of informed consent, regardless of sex; History of total pancreatectomy with baseline C-peptide levels below the lower limit of normal;
2. Post-pancreatectomy hyperglycemia consistent with diagnostic criteria for T3cDM;
3. Stimulated C-peptide level < 0.3 ng/mL at 120 minutes following a mixed meal;
4. HbA1c≥7.5% or TIR < 70% despite intensified insulin therapy;
5. Male participants who are sexually active and not surgically sterilized or whose partners are of childbearing potential must agree to use effective contraception and refrain from sperm donation throughout the study and for at least 6 months thereafter; female participants of childbearing potential must agree to use effective contraception for the duration of the study and for at least 6 months thereafter.
6. Voluntary written informed consent and willingness to comply with the study protocol and visit schedule.

Exclusion criteria

1. Known hemoglobinopathies or moderate-to-severe anemia interfering with HbA1c interpretation;
2. Positive HBsAg or HBcAb with HBV DNA ≥10⁴ copies/mL or ≥2000 IU/mL; Patients with positive HBsAg and HBV DNA <2000 IU/mL must be on antiviral therapy throughout the study. Patients with positive HBcAb and HBV DNA <2000 IU/mL must undergo regular HBV DNA monitoring;
3. Positive HCV antibody with HCV RNA≥10³IU/mL;
4. Positive HIV antibody testing;
5. Active syphilis infection (those with resolved infection may be included);
6. Existence or suspicion of other uncontrollable or untreatable fungal, bacterial, viral or other infections;
7. Uncontrolled hypertension (SBP >160 mmHg and/or DBP >100 mmHg despite stable antihypertensive treatment for ≥4 weeks);
8. History of coagulopathy or long-term anticoagulation therapy (e.g., warfarin) or INR >1.5 (low-dose aspirin permitted);
9. Impaired liver function: AST or ALT >3× ULN Total bilirubin >2× ULN;
10. Impaired renal function with Creatinine clearance <45 mL/min (Cockcroft-Gault formula);
11. History of end-stage heart or lung disease, or cirrhosis;
12. Presence or history of any type of cancer, excluding papillary thyroid cancer cured for more than 1 year;
13. Severe mental/psychological disorders, or severe cognitive impairment
14. Pregnant or lactating women;
15. Other situations or abnormal findings judged by the investigator as unsuitable for participating in the trial.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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29 participants in 1 patient group

HLA-matched pancreatic endocrine organoids transplantation

Experimental group

Description:

Islet cells are isolated from resected pancreatic tissue obtained from patients undergoing surgery, followed by ex vivo expansion and culture. Subsequent procedures include HLA typing, functional assessment of organoid-like structures, and biobanking. After matching for HLA, the cells are administered into patients with type 3c diabetes mellitus (T3cDM) via ultrasound-guided percutaneous transhepatic portal vein catheterization. A 52-week follow-up is conducted to evaluate the safety of the cell therapy and its clinical efficacy in glycemic control.

Treatment:

Procedure: HLA-matched pancreatic endocrine organoids transplantation