Safety and Efficacy of Umbilical Cord Blood Regulatory T Cells Plus Liraglutide on Autoimmune Diabetes
- Conditions
- Type1 Diabetes MellitusAutoimmune Diabetes
- Interventions
- Registration Number
- NCT03011021
- Lead Sponsor
- Second Xiangya Hospital of Central South University
- Brief 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.
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 40
- 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.
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description UCB-Treg 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. UCB-Treg plus Liraglutide UCB-Treg 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. UCB-Treg Insulin Subjects will receive a single infusion of ex vivo expanded Treg product (2 x 10\^6). Insulin will be continued as a routine therapy. Liraglutide Insulin 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. UCB-Treg plus Liraglutide Insulin 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. Insulin Insulin Patients will receive insulin injection as a routine therapy. UCB-Treg plus Liraglutide 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. Liraglutide 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.
- Primary Outcome Measures
Name Time Method Adverse effects 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.
- Secondary Outcome Measures
Name Time Method Change in C-peptide 2 years Measure the C-peptide level after treatment
Life quality evaluation 2 years Number of participants with disturbance of emotion, sleep, resting or energy.
Change in titer of autoantibodies 2 years Measure the titer of antoantibodies of participant after treatment
Change in immune cells diversities and quantities. 2 years Measure the immune cells diversities and quantities after treatment
Change in HbA1C 2 years Measure the HbA1C level after treatment
Change in insulin dose 2 years Measure insulin dose patient used after treatment
Hypoglycaemic events 2 years Measure the number of participants with Hypoglycaemic events
Change in autoimmune-related cytokines 2 years Measure the change of autoimmune- related cytokines after treatment
Trial Locations
- Locations (1)
Institute of Metabolism and Endocrinology, Second Xiangya Hospital, Central South University
🇨🇳Changsha, Hunan, China