Clinical trial NCT05990517: Autologous Transplantation of Expanded Pancreatic Islet Cells (YD01-2022) in Patients
Official title: Evaluation of the Efficacy and Safety of Autologous Transplantation of Expanded Pancreatic Islet Cells (YD01-2022) in Patients With Diabetes Mellitus After Total Pancreatectomy
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Diabetes After Total Pancreatectomy
Lead sponsor: Shanghai Jiao Tong University School of Medicine
Sponsor class: OTHER
First posted: 2023-08-14
Enrollment: 3
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study will evaluate the efficacy and safety of autologous transplantation of expanded pancreatic islet cells in patients with diabetes mellitus after total pancreatectomy.


Eligibility criteria: Inclusion Criteria:

1. Voluntarily sign an informed consent form and comply with the trial treatment plan and visit schedule.

2. Age ≥18 years and ≤60 years on the day of signing the informed consent form, regardless of gender.

3. Diagnosed with chronic pancreatitis and indication for total pancreatectomy. 4. Post-total pancreatectomy, experiencing elevated blood glucose levels and meeting the diagnostic criteria for diabetes (World Health Organization, 2019 edition).

5. Post-mixed meal stimulation, C-peptide level \<0.3 ng/mL at 120 minutes. 6. Sexually active males who are not surgically sterilized or have partners of childbearing potential agree to use effective contraception during the entire trial period and for at least 6 months after the study ends; sexually active females of childbearing potential agree to use effective contraception during the entire study period and for at least 6 months after the study ends.

1. History of diabetes or preoperative diagnosis of hyperglycemia, meeting the diagnostic criteria for diabetes.
2. Previous pancreatic or islet transplantation.
3. Uncontrolled hypertension, such as systolic blood pressure (SBP) \>160 mmHg and/or diastolic blood pressure (DBP) \>100 mmHg despite stable dose (at least 4 weeks) of antihypertensive medication.
4. Known hemoglobin-related diseases, anemia (moderate to severe), or other known hemoglobinopathies that interfere with HbA1c measurement (such as sickle cell disease).
5. Impaired liver or kidney function at screening (reference range from the study center's laboratory): 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 rate \<45 mL/min (calculated by the Cockcroft-Gault formula).
6. Significant albuminuria (urinary albumin excretion rate \>300 mg/g) or history thereof.
7. Uncontrolled thyroid disease or adrenal insufficiency.
8. Positive hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) with peripheral blood hepatitis B virus (HBV) DNA ≥104 copies or ≥2000 IU/mL (HBsAg positive with HBV DNA \<2000 IU/mL (\<104/mL) must receive antiviral treatment throughout the study; HBcAb positive with HBV DNA \<2000 IU/mL (\<104/mL) require regular monitoring of HBV DNA quantification throughout the study); Hepatitis C virus (HCV) antibody positive with peripheral blood HCV RNA ≥103 IU/mL; Human immunodeficiency virus (HIV) antibody positive; Active syphilis infection (cured cases may be included); Cytomegalovirus (CMV) DNA positive; Positive nucleic acid test for novel coronavirus (COVID-19).
9. Severe heart disease or a history of cardiovascular disease within 6 months before screening, including stroke, decompensated heart failure (NYHA class III or IV), myocardial infarction, unstable angina, or coronary artery bypass grafting.
10. Previous history of coagulation disorders or requiring long-term anticoagulant therapy (e.g., warfarin) (low-dose aspirin therapy is allowed) or patients with INR \>1.5.
11. Substance abusers with a history of drug abuse/dependence or drug use within 1 year before screening.
12. Received live virus vaccines within the past 6 months or planned to receive live virus vaccines during the trial or within 1 month after treatment. Live vaccines include, but are not limited to, measles, mumps, rubella, varicella, yellow fever, rabies, Bacillus Calmette-Guérin, typhoid vaccine, COVID-19 vaccine, etc.
13. Previous history of pancreatic cancer, intraductal papillary mucinous neoplasm of the pancreas, end-stage lung disease, or liver cirrhosis.
14. Other abnormal laboratory test results deemed clinically significant by the investigator.
15. Patients with severe mental illness.
16. Participated in a drug or medical device clinical trial within the past 3 months and received investigational drugs or medical devices; or within 5 half-lives of another drug before screening (if the half-life exceeds 3 months).
17. Currently receiving long-term (continuous for ≥14 days) systemic pharmacological doses of glucocorticoids or other medications that may affect the participant's consciousness.
18. Treatment (local, intra-articular, intraocular, or inhalation preparations) for any other factors or diseases not mentioned above, deemed unsuitable for participation in this clinical study by the investigator.

Primary outcomes:
measure: C-peptide change
timeFrame: 12 months post-transplant
Secondary outcomes:
measure: the proportion of subjects with HbA1c ≤7.0% and no severe hypoglycemic events
timeFrame: 52 weeks post-transplant
measure: The proportion of subjects who are insulin-independent
timeFrame: 12 weeks and 52 weeks post-transplant
measure: The percentage reduction in insulin requirement
timeFrame: 12 weeks and 52 weeks post-transplant
measure: Glycemic control (MAGE)
timeFrame: 12 weeks and 52 weeks post-transplant
measure: Evaluation of the severity of hypoglycemia using the Ryan Hypoglycemia Severity Score (HYPO)
timeFrame: baseline and 52 weeks post-transplant
measure: Quality of life score
timeFrame: baseline and 52 weeks post-transplant
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Department of Endocrinology and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao-Tong University
Study officials:
References: