UCMSCs Combined With Allogeneic Islet Transplantation for the Treatment of Diabetes

Investigation of Dose Escalation and Dose Expansion Study on the Safety and Efficacy of Allogeneic Human Umbilical Cord Mesenchymal Stem Cells Combined With Allogeneic Islet Transplantation for the Treatment of Diabetes

The aim is to Investigate the safety and efficacy of Portal vein infusion Allogeneic Human umbilical cord mesenchymal stem cells combined with Allogeneic islet transplantation for the treatment of diabetes

Study Overview

• Status: Recruiting
• Conditions: Diabetes
• Intervention / Treatment: Drug: human umbilical cord mesenchymal stem cells; Drug: allogeneic islet

Detailed Description

This is an investigator-initiated trial (IIT). The first part is an open-label, dose-escalation study involving 9 patients between the ages of 18 and 70. The second part is a non-randomized, active comparator-controlled IIT with a parallel design, comparing allogeneic islet transplantation combined with human umbilical cord mesenchymal stem cells (hUCMSCs) to allogeneic islet transplantation alone in patients with diabetes.Besides safety, preservation of endogenous insulin production (measured as C-peptide concentrations) together with metabolic control, diabetes treatment satisfaction and immunological profile will be assessed.

• Study Type: Interventional
• Enrollment (Estimated): 16
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Hao Yin; Phone Number: 13901677738; Email: yinhaoshanghai@163.com

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China
      • Recruiting
      • Shanghai Changzheng Hospital
      • Contact: Hao Yin; Phone Number: 13901677738; Email: yinhaoshanghai@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Meets the 1999 World Health Organization diagnostic criteria for diabetes.
2. Aged 18-70, no gender restriction.
3. Islet function failure: fasting C-peptide < 0.1 nmol/L, 2-hour postprandial C-peptide < 0.2 nmol/L, and HbA1c ≥ 7%.

4. Meets the indications for islet transplantation alone:

   i. Type 1 diabetes patients who experience unstable blood glucose despite strict insulin therapy, including frequent hypoglycemia or at least one severe hypoglycemic event in the past 12 months, or those with serious complications in other organs such as the kidneys; ii. Type 2 diabetes progressing to islet failure with poor blood glucose control as described above; iii. Patients with chronic pancreatitis or non-malignant pancreatic tumors who have undergone total or near-total pancreatectomy may receive autologous islet transplantation concurrently or allogeneic islet transplantation later.

5. The patient and their family or legal guardian voluntarily consent to stem cell transplantation therapy and sign the informed consent form.

Exclusion Criteria:

1. Diabetic ketoacidosis that is not yet controlled.
2. Severe allergic constitution, meaning prone to allergic reactions without a clear and identifiable cause.
3. BMI < 14 or > 35.
4. Severe anemia (hemoglobin < 8 g/dL in males, < 7 g/dL in females).
5. HIV-positive, carriers of viral hepatitis or in the active phase, or other uncontrolled infectious diseases.
6. History of acute pancreatitis, pulmonary embolism, or other thrombotic diseases, as well as severe heart, liver, kidney, respiratory, or neurological diseases.
7. Patients with gestational diabetes, monogenic diabetes, diabetes due to pancreatic damage, or other secondary diabetes (e.g., diabetes caused by Cushing's syndrome, thyroid dysfunction, or acromegaly).
8. Pregnant women or those planning pregnancy within 3 months before or after treatment, and women who are breastfeeding.
9. Patients with mental illness, alcohol or drug abuse, who are unable to cooperate with treatment.
10. Known or suspected tumors.
11. History of other autoimmune diseases or hematological disorders.
12. Any other clinical conditions that, in the investigator's judgment, may pose a risk to the participant's safety.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental; allogeneic islet combined with hUCMSCs	Drug: human umbilical cord mesenchymal stem cells; Portal vein infusion human umbilical cord mesenchymal stem cells; Drug: allogeneic islet; Portal vein infusion of allogeneic islet
Active Comparator: Comparator; allogeneic islet	Drug: allogeneic islet; Portal vein infusion of allogeneic islet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety assessment: Registration of adverse events	Changes in safety parameters of patients during the study period since baseline. Measured through the registration of adverse events.	Throughout the study until Week 52
Efficacy Assessment: Evaluation of islet function	Change of C-peptide Area Under the Curve (AUC) (0-120 min) for Mixed Meal Tolerance Test (MMTT) at Week 52 compared to test performed before start of treatment.	Throughout the study until Week 52

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy Assessment: HbA1c	Changes in patient HbA1c levels from baseline during the study period	Week 52
Dose of exogenous insulin	Changes in daily exogenous insulin requirements during the study period	Week 52

Collaborators and Investigators

• Sponsor: Shanghai Changzheng Hospital
• Investigators: Principal Investigator: Hao Yin, Shanghai Changzheng Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): December 30, 2024
• Primary Completion (Estimated): July 30, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: October 10, 2024
• First Submitted That Met QC Criteria: December 22, 2024
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 22, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Metabolic Diseases; Glucose Metabolism Disorders; Diabetes Mellitus
• Other Study ID Numbers: CZYZ-CTIM-2023-IIT

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

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