safety and efficacy of umbilical cord blood regulatory t cells plus liraglutide on autoimmune diabetes

Conditions: Type1 Diabetes Mellitus; Autoimmune Diabetes

Summary: 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.

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.

Eligibility criteria:
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.

Keywords: autoimmune diabetes umbilical cord blood regulatory t lymphocyte liraglutide