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

Central South University

Status and phase: Enrolling; Phase 2; Phase 1

Conditions: Type1 Diabetes Mellitus; Autoimmune Diabetes

Treatments: Drug: Insulin; Drug: Liraglutide; Biological: UCB-Treg

Study type: Interventional

Funder types: Other

Identifiers

NCT03011021

0001

Details and patient eligibility

About

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.

Full 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.

Enrollment: 40 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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40 participants in 4 patient groups

UCB-Treg plus Liraglutide

Experimental group

Description:

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.

Treatment:

Drug: Liraglutide

Drug: Insulin

Biological: UCB-Treg

UCB-Treg

Active Comparator group

Description:

Subjects will receive a single infusion of ex vivo expanded Treg product (2 x 10\^6). Insulin will be continued as a routine therapy.

Treatment:

Drug: Insulin

Biological: UCB-Treg

Liraglutide

Active Comparator group

Description:

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.

Treatment:

Drug: Liraglutide

Drug: Insulin

Insulin

Active Comparator group

Description:

Patients will receive insulin injection as a routine therapy.

Treatment:

Drug: Insulin