Clinical trial NCT06991829: Clinical Study on the Safety and Efficacy of Immunophenotyped Pancreatic Endocrine Organoid Bank in Treating Patients With T3c Diabetes
Official title: Clinical Study on the Safety and Efficacy of Immunophenotyped Pancreatic Endocrine Organoid Bank in Treating Patients With T3c Diabetes
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: EARLY_PHASE1
Conditions: Diabetes Mellitus
Keywords: type 3c diabetes mellitus
pancreatic endocrine organoids
Islet Transplantation
HLA-immunotyped
Lead sponsor: Shanghai Zhongshan Hospital
Sponsor class: OTHER
Collaborators: name: Shanghai Newislet Therapeutics Co., Ltd.
First posted: 2025-05-28
Enrollment: 29
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
Intervention model description: A single-arm clinical trial is designed to evaluate whether transplantation of HLA-matched pancreatic endocrine organoids can effectively lower blood glucose levels in patients with diabetes following pancreatectomy. The trial employs Simon's Two-Stage Optimal Design to determine sample size, with parameters: P0 = 0.10 (null hypothesis), P1 = 0.30 (alternative hypothesis), α = 0.05, and β = 0.20. Given the lack of definitive treatments and the first-in-human nature of this intervention, 10 patients will be enrolled in the first stage. If ≥2 achieve treatment success, the trial proceeds to stage two; otherwise, it stops. In stage two, 19 more patients will be enrolled (total n=29). If ≥6 patients achieve treatment success, the therapy is considered effective; if \<6, it is considered ineffective.
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Proportion of Participants with ≥50% Reduction in Daily Insulin Dose at Week 52 Post-Transplantation Compared to Baseline
timeFrame: From enrollment to the end of treatment at 52 weeks post-transplantation
measure: Proportion of Participants with HbA1c < 7.0% at Week 52 Post-Transplantation
timeFrame: From enrollment to the end of treatment at 52 weeks post-transplantation
measure: Number of Participants with No Episodes of Severe Hypoglycemia Between Weeks 12 and 52 Post-Transplantation
timeFrame: From Week 12 to Week 52 post-transplantation
Secondary outcomes:
measure: Proportion of Participants with HbA1c < 7.0% at Weeks 12, 26, and 52 Post-Transplantation
timeFrame: Weeks 12, 26, and 52 post-transplantation
measure: Proportion of Participants with ≥50% Reduction in Daily Insulin Dose at Weeks 12, 26, and 52 Post-Transplantation
timeFrame: Weeks 12, 26, and 52 post-transplantation
measure: Proportion of Participants Achieving Insulin Independence at Weeks 26 and 52 Post-Transplantation
timeFrame: Weeks 26 and 52 post-transplantation
measure: Proportion of Participants with Stimulated C-Peptide Peak > 0.3 ng/mL Following a Mixed Meal Tolerance Test at Weeks 12, 26, and 52
timeFrame: Weeks 12, 26, and 52 post-transplantation
measure: Time-in-Range (TIR) at Weeks 12, 26, and 52 Post-Transplantation
timeFrame: Weeks 12, 26, and 52 post-transplantation
measure: Mean Amplitude of Glycemic Excursions (MAGE) at Weeks 12, 26, and 52 Post-Transplantation
timeFrame: Weeks 12, 26, and 52 post-transplantation
measure: Cumulative Number of Hypoglycemic Episodes at Weeks 12, 26, and 52 Post-Transplantation
timeFrame: Weeks 12, 26, and 52 post-transplantation
measure: Number of Adverse Events (AEs), Serious Adverse Events (SAEs), and Adverse Events of Special Interest (AESIs)
timeFrame: From enrollment to Week 52 post-transplantation.
measure: Change in Quality of Life Scores from Baseline to Week 52 Post-Transplantation
timeFrame: From enrollment to the end of treatment at 52 weeks post-transplantation
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Zhongshan Hospital, Fudan University
state: Shanghai
Study officials:
References: