Phase 1/ Phase 2 Study of the Therapeutic Effect of Ex-vivo Expanded Umbilical Cord Blood Regulatory T Cells With Liraglutide on Autoimmune Diabetes
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Adverse effects
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
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.
干预措施: Insulin (Drug)
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.
干预措施: Liraglutide (Drug)
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.
干预措施: UCB-Treg (Biological)
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.
干预措施: UCB-Treg (Biological)
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.
干预措施: Insulin (Drug)
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.
干预措施: Liraglutide (Drug)
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.
干预措施: Insulin (Drug)
Insulin
Patients will receive insulin injection as a routine therapy.
干预措施: Insulin (Drug)
结局指标
主要结局
Adverse effects
时间窗: 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.
次要结局
- Change in C-peptide(2 years)
- Life quality evaluation(2 years)
- Change in titer of autoantibodies(2 years)
- Change in immune cells diversities and quantities.(2 years)
- Change in HbA1C(2 years)
- Change in insulin dose(2 years)
- Hypoglycaemic events(2 years)
- Change in autoimmune-related cytokines(2 years)
研究者
Zhiguang Zhou
Principal Investigator
Second Xiangya Hospital of Central South University