Allogeneic Regenerative Islet Transplantation for the Treatment of Brittle Type 1 Diabetes Mellitus

Allogeneic Regenerative Islet Transplantation for the Treatment of Brittle Type 1 Diabetes Mellitus: A Clinical Study Evaluating Safety and Efficacy

This is a single-center, single-arm Phase Investigational Intervention Trial (IIT) clinical trial aimed at evaluating the safety and efficacy of allogeneic regenerative islet transplantation for the treatment of brittle type 1 diabetes mellitus. Eighteen patients with brittle type 1 diabetes mellitus, who have inadequate blood glucose control despite intensified exogenous insulin therapy, will be enrolled. The primary endpoint is defined as the safety and improvement in blood glucose levels of the 12 months after allogeneic regenerative islet transplantation.

Study Overview

• Status: Recruiting
• Conditions: Brittle Type 1 Diabetes Mellitus
• Intervention / Treatment: Procedure: The method of islet transplantation is through percutaneous transhepatic portal vein puncture.

• Study Type: Interventional
• Enrollment (Estimated): 18
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Hao Yin; Phone Number: 13901677738; Email: yinhaoshanghai@163.com
• Study Contact Backup: Name: Hao Yin; 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: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age 6-65 years, gender not specified.
2. Despite intensified exogenous insulin therapy, blood glucose control remains inadequate [glycated hemoglobin ≥7.5%, or TIR (time in range) <70%].
3. Able and willing to use the blood glucose meter provided by the sponsor, conduct self-blood glucose monitoring as required, and complete the patient log as instructed.
4. Fertile eligible subjects (male or female) must agree to use a reliable contraceptive method (hormonal or barrier method or abstinence) during the trial and for at least 90 days after the last dose; premenopausal female patients must have a negative pregnancy test before enrollment.
5. Diagnosed with type 1 diabetes for at least 1 year based on the World Health Organization (WHO) disease diagnostic criteria, and at least one positive result for diabetes-related autoantibodies [glutamic acid decarboxylase autoantibody (GADA), insulinoma-associated-2 autoantibody (IA-2A), insulin autoantibody (IAA), islet cell antibody (ICA), zinc transporter 8 antibody (ZaT8A)]. Experiencing two or more severe hypoglycemic events in the past year, with at least one severe hypoglycemic event in the past 3 months (severe hypoglycemia defined as blood glucose below 2.9 mmol/L or inability to self-correct during hypoglycemia).
6. Voluntarily participate and sign the informed consent form.

Exclusion Criteria:

1. Uncontrolled systemic infections, including but not limited to pulmonary tuberculosis, active hepatitis, a history of positive human immunodeficiency virus (HIV) testing, and positive syphilis treponemal antibody (TP);
2. Presence of significant organic lesions in vital organs such as the heart, lungs, or brain;
3. Complications of severe diabetes, including but not limited to retinal hemorrhage, diabetic foot, etc.;
4. Liver function tests with total bilirubin, ALT, and AST ≥2×ULN, and failure to normalize after drug treatment;
5. Untreated cancer or less than 1 year since cure;
6. Severe gastrointestinal dysfunction, gastrointestinal immune diseases, and inability to take immunosuppressant;
7. History of smoking, alcohol abuse, or drug misuse;
8. Severe mental or psychological disorders;
9. Various advanced metabolic diseases (such as hyperuricemia, etc.);
10. Participation in other clinical trials in the 3 months prior to enrollment;
11. Patients requiring long-term oral/intravenous administration of high-dose glucocorticoids due to various diseases;
12. Pregnant or lactating women;
13. Investigator judgment indicating clear evidence of severe, active, uncontrolled endocrine or autoimmune abnormalities other than type 1 diabetes;
14. Other situations judged by the investigator as unsuitable for participation in the trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Allogeneic Regenerative Islet Transplantation for the Treatment of Brittle Type 1 Diabetes Mellitus

Procedure: The method of islet transplantation is through percutaneous transhepatic portal vein puncture.; The method of islet transplantation is through percutaneous transhepatic portal vein puncture.After transplantation, rabbit anti human thymocyte immunoglobulin (ATG) or basiliximab was used as induction therapy and low-dose tacrolimus combined with sirolimus or mycophenolate mofetil were used as immunosuppressive maintenance therapy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time in Range	Changes in patient blood glucose time in range from baseline	up to 12 months
HbA1c	Changes in patient HbA1c levels from baseline during the study period	up to 12 months
C-peptide	Changes in patient fasting and postprandial C-peptide/insulin from baseline during the study period	up to 12 months
insulin	Changes in patient fasting and postprandial insulin from baseline during the study period	up to 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose of exogenous insulin	Changes in daily exogenous insulin requirements during the study period	up to 12 months

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): September 14, 2021
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): September 1, 2026

Study Registration Dates

• First Submitted: December 13, 2023
• First Submitted That Met QC Criteria: December 25, 2023
• First Posted (Actual): January 9, 2024

Study Record Updates

• Last Update Posted (Actual): January 9, 2024
• Last Update Submitted That Met QC Criteria: December 25, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1
• Other Study ID Numbers: ZXHZ-IIT-02

Drug and device information, study documents

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