Autoimmune Diabetes, Type1 Diabetes Mellitus
Conditions
Keywords
Autoimmune Diabetes, Umbilical Cord Blood Regulatory T Lymphocyte, Liraglutide
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.
Interventions
DRUGLiraglutide
Dose escalation of Liraglutide starts from 0.6 mg up to 1.2 mg per day.
BIOLOGICALUCB-Treg
Receive Treg infusion: 1\ 5\*10\^6/kg b.w. in 100ml normal saline
DRUGInsulin
Receive insulin following clinician's instruction.
Sponsors
Second Xiangya Hospital of Central South University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Change in HbA1C | 2 years | Measure the HbA1C level after treatment |
| Change in C-peptide | 2 years | Measure the C-peptide 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 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 autoimmune-related cytokines | 2 years | Measure the change of autoimmune- related cytokines after treatment |
| Life quality evaluation | 2 years | Number of participants with disturbance of emotion, sleep, resting or energy. |
Countries
China
Contacts
Primary ContactZhiguang Zhou, MD/PhD
Outcome results
None listed