Safety and Efficacy of OCN19-overexpressed Human Umbilical Cord-derived Mesenchymal Stem Cells in the Treatment of Refractory Type 2 Diabetes Mellitus

Umbilical cord mesenchymal stem cell injection expressing OCN19, while playing the role of MSCs, can directly stimulate the expression of insulin gene and the division and proliferation of islet beta cells, which is expected to further enhance the therapeutic effect of stem cells. In non-clinical studies, it was found that MSCs expressing OCN19 had better hypoglycemic effect than MSCs

Study Overview

• Status: Recruiting
• Conditions: Diabetes; Type 2 Diabetes
• Intervention / Treatment: Biological: albumin injection; Biological: Mesenchymal stem cells; Biological: mesenchymal stem cells with OCN-19

• Study Type: Interventional
• Enrollment (Estimated): 10
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: jin lu; Phone Number: 021-18801784133; Email: 18801784133@163.com

Study Locations

• China
  • Shanghai, China
    • Recruiting
    • Changhai Hospital
    • Contact: jin lu; Email: 18801784133@163.com

Participation Criteria

Eligibility Criteria

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

Description

1. Inclusion Criteria:

   1. Accoding to WHO diagnostic standards, patients with type 2 diabetes (fasting blood glucose ≥ 7.0 mmol/L), 30-75 years old, regardless of gender;
   2. Able to clearly understand the purpose of clinical trials and comply with trial requirements, willing to participate in this study, and sign an informed consent form;
   3. 20kg/m2 ≤ Body Mass Index (BMI) ≤ 30 kg/m2;
   4. 7.5% ≤ glycated hemoglobin ≤ 10%;
   5. Insulin should be subcutaneously injected for more than six months, and insulin and/or other oral hypoglycemic drugs (limited to metformin only) should be used α The dosage of glycosidase inhibitors remained stable for the first 3 months before randomization;
   6. During the study period, all males and females with reproductive potential were willing to accept the use of efficient contraceptive methods.

2. Exclusion Criteria:

   1. 1 Type diabetes, pregnancy diabetes or other special type diabetes patients;
   2. Patients with severe allergic constitution or allergic to any ingredients used in cell culture;
   3. Patients who have used drugs that affect glucose metabolism within the past month, such as glucocorticoids, thiazide diuretics, oral contraceptives, tricyclic antidepressants, etc;
   4. Screening the patients with acute complications such as diabetes ketoacidosis and non ketotic hyperosmolar syndrome in recent 6 months;
   5. Serious cardiovascular and cerebrovascular events such as NYHA grade III or IV heart failure, myocardial infarction, cerebral infarction, and cerebral hemorrhage occurred within the past 6 months;
   6. Patients with abnormal blood routine (including white blood cell or neutrophil count below the lower limit of normal, abnormal platelet count, and hemorrhagic disease);
   7. Patients with liver and kidney dysfunction: such as serum bilirubin TBIL exceeding the upper limit of normal by 1.5 times, AST and ALT exceeding the upper limit of normal by 2.5 times, and serum creatinine exceeding 1.5 mg/dl for males and 1.4 mg/dl for females;
   8. Patients with other serious systemic diseases (such as malignant tumors, central nervous system, cardiovascular system, blood system, digestive system, endocrine system, respiratory system, urogenital system, immune system, etc.);
   9. Individuals who are currently using systemic hormones (such as glucocorticoids), immunosuppressants, or cytotoxic therapy;
   10. Patients who received antibiotic treatment within the three months prior to study registration;
   11. Patients who have received live or attenuated vaccines within 4 weeks prior to registration, or plan to receive live or attenuated vaccines during the study period;
   12. Patients who are positive for HbsAg, Anti HCV, HIV or syphilis;
   13. Patients with active infection (such as hepatitis B or hepatitis C, tuberculosis) requiring treatment;
   14. Fever related diseases of unknown origin;
   15. Disabled patients (blind, deaf, mute, intellectually disabled, physically disabled) and individuals with mental illnesses;
   16. Patients who use drugs or have a history of adverse drug abuse and alcohol dependence within 5 years (with mental or substance abuse disorders that may interfere with the requirements of the trial);
   17. Patients of childbearing age who are pregnant or lack effective contraceptive measures or have a pregnancy plan, as well as breastfeeding patients;
   18. Patients who have received other stem cell treatments or participated in other clinical studies within the first three months of screening;
   19. Patients who have not recovered due to adverse events (≥ level 2) caused by drug treatment within 4 weeks prior to the start of the study;
   20. Patients with congenital or acquired immune dysfunction or a history of organ transplantation;
   21. Patients with other serious diseases that may affect infusion results;
   22. According to the judgment of the researchers, patients whose clinical conditions are not suitable for inclusion in this study.-

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: The placebo group; The control group was given albumin	Biological: albumin injection; Placebo
Active Comparator: The control group; The control group was given mesenchymal stem cells	Biological: Mesenchymal stem cells; Ordinary mesenchymal stem cells were given
Experimental: The experimental group; The experimental group was given OCN-19 stem cells	Biological: mesenchymal stem cells with OCN-19; The patient received mesenchymal stem cells with OCN-19 three times

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Daily insulin dose is used	From enrollment to 1 month, 3 months, 6 months and 1 year after treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in Fasting Blood Glucose Levels Over Time	Fasting Blood Glucose (FBG) Definition: Blood sugar levels measured after fasting for at least 8 hours. Methods of measurement: Blood samples are determined using standardized laboratory analytical methods. Unit: Expressed in mg/dL (mg/dL). Time point: Measurements were taken at baseline, 12 and 24 weeks post-treatment. Goal: The target fasting blood glucose level in the study was <100 mg/dL.	From enrollment to 1 month, 3 months, 6 months and 1 year after treatment
Concentration of Hemoglobin A1c in Participants	Definition: The proportion of hemoglobin bound to glucose that reflects average blood sugar levels over the past 2-3 months. Methods of measurement: Blood samples were analyzed using high performance liquid chromatography (HPLC). Unit: Expressed in percentage (%). Time point: Measurements were taken at baseline, 12 and 24 weeks post-treatment. Target: The target HbA1c level in the study was <7.0%.	From enrollment to 3 months, 6 months and 1 year after treatment
Concentration of fasting c-peptide in Participants	Definition: Clarify the definition of fasting C-peptide, which usually refers to the level of C-peptide measured in the fasting state, C-peptide is a by-product of insulin synthesis and reflects the function of islet beta cells. Measurement methods: Describe specific methods used to measure C-peptide, such as enzyme-linked immunosorbent assay (ELISA) . Units: Usually expressed in picmole/liter (pmol/L) or nanogram/milliliter (ng/mL).	From enrollment to 1 month, 3 months, 6 months and 1 year after treatment
Concentration of Glycated albumin in Participants	Definition: The proportion of albumin bound to glucose, reflecting the average blood sugar level over the past 2-3 weeks. Methods of measurement: Blood samples were analyzed using immunoassays. Unit: Expressed in percentage (%)	From enrollment to 1 month, 3 months, 6 months and 1 year after treatment
Concentration of 2-hour postprandial C-peptide in Participants	Definition: 2-hour postprandial C-peptide refers to the level of C-peptide measured 2 hours after eating, C-peptide is a by-product of insulin synthesis, reflecting the function of islet beta cells and insulin secretion capacity. Methods of measurement: Blood samples are analyzed using standardized methods such as enzyme-linked immunosorbent assay (ELISA) or radioimmunoassay (RIA). Units: Usually expressed in picomoles per liter (pmol/L) or nanograms per milliliter (ng/mL).	From enrollment to 1 month, 3 months, 6 months and 1 year after treatment
Concentration of total cholesterol in Participants	Definition: Total cholesterol is the sum of all cholesterol in the blood, including low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and very low-density lipoprotein cholesterol (VLDL-C). Total cholesterol level is an important indicator of cardiovascular health. Methods of measurement: Blood samples are tested using standardized blood chemical analysis methods, usually enzymatic or chemical. Unit: Usually expressed in milligrams per deciliter (mg/dL). Target value: The normal range of total cholesterol in the study is usually: Ideal level: <200 mg/dL Marginal high levels: 200-239 mg/dL High level: ≥240 mg/dL	From enrollment to 1 month, 3 months, 6 months and 1 year after treatment
Concentration of LDL in Participants	Low Density Lipoprotein Cholesterol (LDL-C) Definition: Low-density lipoprotein cholesterol (LDL-C) is a major form of cholesterol transport in the blood and is often referred to as "bad cholesterol." High levels of LDL-C are associated with an increased risk of cardiovascular disease, atherosclerosis, and other cardiovascular events. Methods of measurement: Blood samples are tested using standardized blood chemical analysis methods, usually enzymatic or chemical. Unit: Usually expressed in milligrams per deciliter (mg/dL). Target values: The normal range of LDL-C in studies is usually: Ideal level: <100 mg/dL Near ideal/borderline high l	From enrollment to 1 month, 3 months, 6 months and 1 year after treatment

Collaborators and Investigators

• Sponsor: Lu jin ，MD

Study record dates

Study Major Dates

• Study Start (Actual): November 6, 2023
• Primary Completion (Estimated): December 12, 2028
• Study Completion (Estimated): December 12, 2029

Study Registration Dates

• First Submitted: November 27, 2024
• First Submitted That Met QC Criteria: December 10, 2024
• First Posted (Actual): December 11, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 12, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Metabolic Diseases; Glucose Metabolism Disorders; Diabetes Mellitus, Type 2; Diabetes Mellitus
• Other Study ID Numbers: CHEC2023-226

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No