Immunotherapy with Autologous Tregs in T1DM

Clinical Safety and Therapeutic Effects of Autologous Tregs in T1DM

Type 1 diabetes (T1D) is an autoimmune disease characterized by a progressive immune distruction of pancreat beta cells and deterioration of endogenous insulin secretion. Regulatory T cells (Treg) are fuctionally deficient in T1D, leading to the loss of immune tolerance to the islets and the initiation of an autoimmune attack. Previouse studies have revealed the potential theraputic effects of autologous Treg transplantation in T1D. We have modified the preparation protocol for autologous Tregs. The purpose of this study is to assess the safety and effect of autologous Treg therapy in patients with T1D.

Study Overview

• Status: Recruiting
• Conditions: Type 1 Diabetes Mellitus
• Intervention / Treatment: Biological: Ex vivo Expanded Human Autologous Regulatory T Cells; Other: Routine Care

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Dr. Lu, MD; Phone Number: 0086-025-868182432; Email: lujing@njglyy.com

Study Locations

• China
  • Jiangsu
    • Nanjing, Jiangsu, China
      • Recruiting
      • The Department of Endocrinology, The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
      • Contact: Dr. Lu, medical doctor; Phone Number: 0086-025-68182432; Email: lujing@njglyy.com
      • Contact: Prof. Zhu, Medical doctor; Phone Number: 0086-025-68182432; Email: zhudalong@nju.edu.cn
      • Contact: Prof. Zhu, MD
      • Contact: Prof. Zhou, PhD
      • Contact: Dr. Lu, MD

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Meet the diagnostic criteria of T1DM based on the 2021 version of the Chinese Guidelines for Diagnosis and Treatment of Type 1 Diabetes;
• Aged 8 to 65 years;
• At least one islet autoantibody positive and/or fasting C-peptide does not exceed 300pmol/L;
• Must be capable of providing written, signed, and dated informed consent and willing to comply with research requirements in the study.

Exclusion Criteria:

• The condition of diabetic ketoacidosis has not been controlled;
• Severe allergic constitution;
• Known or suspected tumor;
• Acute pancreatitis, and severe heart, liver, kidney, rheumatic immune, respiratory, nervous or infectious diseases.
• Suffering from gestational diabetes mellitus, single gene mutation diabetes mellitus, diabetes mellitus caused by pancreatic damage or other secondary diabetes mellitus (such as diabetes mellitus caused by Cushing's syndrome, thyroid dysfunction or acromegaly, etc.);
• Women who are pregnant or have a pregnancy plan before and after treatment, and women who are breastfeeding.
• Mental illness, alcohol or drug abuse, unable to cooperate with treatment;
• According to the judgment of the investigator, there are other clinical conditions that may endanger the safety of the subjects.

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: Treg Group; Participants in this group are transplanted with expanded autologous Tregs in addition to routine therapy for T1DM.	Biological: Ex vivo Expanded Human Autologous Regulatory T Cells; Peripheral blood component donation is used to collect Treg cells for ex vivo expansion, with technical guidance provided by the Center for Biotechnology Drug Development at the Shanghai Institute of Materia Medica, Chinese Academy of Sciences.; Other: Routine Care; Routine care is provided to all participants according to clinical guidelines for T1DM.
Other: Control Group; Participants in this group receive only routine therapy for T1DM.	Other: Routine Care; Routine care is provided to all participants according to clinical guidelines for T1DM.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of Participants with adverse events, laboratory abnormalities and other signs of toxicity.	From enrollment to the end of treatment at 1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Therapeutic effects on diabetes-related outcomes	Therapeutic effects on diabetes-related outcomes 1 year after intervention include: 1) C-peptide response during mixed meal tolerance test, reported as the change from baseline in the fasting level, postprandial level and area under the curve; 2) Insulin Use; 3) Hemoglobin A1c.	From enrollment to the end of treatment at 1 year

Collaborators and Investigators

• Sponsor: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
• Collaborators: Shanghai Institute of Materia Medica, Chinese Academy of Sciences

Study record dates

Study Major Dates

• Study Start (Actual): April 12, 2023
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: November 26, 2024
• First Submitted That Met QC Criteria: November 26, 2024
• First Posted (Estimated): November 27, 2024

Study Record Updates

• Last Update Posted (Estimated): November 27, 2024
• Last Update Submitted That Met QC Criteria: November 26, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Metabolic Diseases; Autoimmune Diseases; Immune System Diseases; Glucose Metabolism Disorders; Diabetes Mellitus; Diabetes Mellitus, Type 1
• Other Study ID Numbers: 2021-427-TREG

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

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