Safety and Efficacy of Umbilical Cord Blood Regulatory T Cells Plus Liraglutide on Autoimmune Diabetes

March 13, 2023 updated by: Zhiguang Zhou, Second Xiangya Hospital of Central South University

Phase 1/ Phase 2 Study of the Therapeutic Effect of Ex-vivo Expanded Umbilical Cord Blood Regulatory T Cells With Liraglutide on Autoimmune Diabetes

The purpose of this study is to investigate the safety and therapeutic effect of ex-vivo expanded umbilical cord blood regulatory T cells adjunct with Liraglutide on autoimmune diabetes.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Autoimmune Diabetes Mellitus (AIDM) is a subtype of diabetes mellitus caused by autoimmune destruction of beta cells in the islet, including Type 1 diabetes and Latent Autoimmune Diabetes in Adults (LADA). Insulin has been used as a routine therapy for AIDM to alleviate the hyperglycemic status, yet cannot effectively prevent the progressing destruction of beta cells or preserve its function. Regulatory T cells expanded from umbilical cord blood (UCB-Treg) ex-vivo have shown strong capacity to control immune responses in autoimmune diseases, offering a hopeful therapeutic way for AIDM. Glucagon-like peptide (GLP-1) analog Liraglutide has been tested in large-scale clinical trial to prove its various benefits for beta cells and glucolipid metabolism in Type 2 diabetes and obesity patients. However, its clinical application in AIDM is not well-defined so far. The aim of this study is to investigate the potential use of Liraglutide with UCB-Treg infusion in AIDM and examine the safety and efficacy of this new therapy.

Study Type

Interventional

Enrollment (Anticipated)

40

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
    • Hunan
      • Changsha, Hunan, China, 410011
        • Recruiting
        • Institute of Metabolism and Endocrinology, Second Xiangya Hospital, Central South University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Type 1 diabetes according to ADA criteria <3 years.
  • Age≥ 18 years.
  • Positive for at least one of the anti-islet autoantibodies: GADA, IA2A, ZnT8A
  • Fasting or postprandial plasma C-peptide more than 100 pmol/L
  • Written informed consent from the patient or family representative.

Exclusion Criteria:

  • History or family history of medullary thyroid carcinoma or MEN 2 syndrome;
  • History of chronic or acute pancreatitis;
  • Allergic to liraglutide or any components in Victoza®;
  • Hepatic abnormalities (transaminase > 2 times normal);
  • Renal impairments (serum creatinine >133 umol/L);
  • Cardiovascular diseases (hypertension, coronary heart disease, etc.);
  • Presence of anemia (Hb ≤100g/L), leukopenia (<3.5×109/L);
  • Presence of disorder in coagulation or anticoagulation, or thrombocytopenia (platelets <100×109/L);
  • Presence of acute metabolic disorders; In the case of acute ketone acidosis, with blood ketone over 0.3mmol/L and pH lower than 7.30;
  • Presence of any kind of chronic infection or immune deficiency, including hepatitis B, hepatitis C, HIV, syphilis or tuberculosis, etc.;
  • Chronic use of systemic glucocorticoids or other immunosuppressive agents for over 3 months;
  • Any history of malignancy;
  • Female patients who are pregnant or breastfeeding; any female who is unwilling to use a reliable and effective form of contraception for 2 years after recruitment;
  • Presence of any infectious diseases, including active skin infections, flu, fever, upper or lower respiratory tract infections; those who wish to participate in the study should keep the infection under control for at least 1 week before receiving Treg product infusion;
  • Any medical condition that, in the opinion of the investigator, will interfere with safe participation in the trial.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Insulin
Patients will receive insulin injection as a routine therapy.
Drug: Insulin
Receive insulin following clinician's instruction.
Experimental: UCB-Treg plus Liraglutide
Subjects will receive a single infusion of ex vivo expanded umbilical cord blood derived Treg product (2 x 10^6). Dose escalation of liraglutide up to 1.2 mg will be started 3 days after Treg infusion only if no severe side effects showed. Subjects continue to receive the reached liraglutide dose once daily for 6 months thereafter. Insulin will be continued as a routine therapy.
Drug: Insulin
Receive insulin following clinician's instruction.
Drug: Liraglutide
Dose escalation of Liraglutide starts from 0.6 mg up to 1.2 mg per day.
Biological: UCB-Treg
Receive Treg infusion: 1~5*10^6/kg b.w. in 100ml normal saline
Active Comparator: UCB-Treg
Subjects will receive a single infusion of ex vivo expanded Treg product (2 x 10^6). Insulin will be continued as a routine therapy.
Drug: Insulin
Receive insulin following clinician's instruction.
Biological: UCB-Treg
Receive Treg infusion: 1~5*10^6/kg b.w. in 100ml normal saline
Active Comparator: Liraglutide
Patients will be subjected to a dose escalation of liraglutide up to 1.2 mg, then continue to receive the reached liraglutide dose once daily for 6 months thereafter. Insulin will be continued as routine therapy.
Drug: Insulin
Receive insulin following clinician's instruction.
Drug: Liraglutide
Dose escalation of Liraglutide starts from 0.6 mg up to 1.2 mg per day.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Adverse effects
Time Frame: 2 years
Primary outcome measures will be the number of participants with adverse events, laboratory abnormalities and other signs of toxicity. Particular focus will be on the number and severity of infusion reactions, complications related to infection, and any potential negative impact on the course of diabetes.
2 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in HbA1C
Time Frame: 2 years
Measure the HbA1C level after treatment
2 years
Change in C-peptide
Time Frame: 2 years
Measure the C-peptide level after treatment
2 years
Change in insulin dose
Time Frame: 2 years
Measure insulin dose patient used after treatment
2 years
Hypoglycaemic events
Time Frame: 2 years
Measure the number of participants with Hypoglycaemic events
2 years
Change in titer of autoantibodies
Time Frame: 2 years
Measure the titer of antoantibodies of participant after treatment
2 years
Change in immune cells diversities and quantities.
Time Frame: 2 years
Measure the immune cells diversities and quantities after treatment
2 years
Change in autoimmune-related cytokines
Time Frame: 2 years
Measure the change of autoimmune- related cytokines after treatment
2 years
Life quality evaluation
Time Frame: 2 years
Number of participants with disturbance of emotion, sleep, resting or energy.
2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Second Xiangya Hospital of Central South University

Investigators

  • Principal Investigator: Zhiguang Zhou, MD/PhD, Second Xiangya Hospital
  • Principal Investigator: Haibo Yu, MD/PhD, Second Xiangya Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2017

Primary Completion (Anticipated)

June 1, 2025

Study Completion (Anticipated)

June 1, 2025

Study Registration Dates

First Submitted

January 2, 2017

First Submitted That Met QC Criteria

January 3, 2017

First Posted (Estimate)

January 5, 2017

Study Record Updates

Last Update Posted (Actual)

March 14, 2023

Last Update Submitted That Met QC Criteria

March 13, 2023

Last Verified

March 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 0001 (Researcher)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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