Clinical trial NCT03011021: Safety and Efficacy of Umbilical Cord Blood Regulatory T Cells Plus Liraglutide on Autoimmune Diabetes
Official title: Phase 1/ Phase 2 Study of the Therapeutic Effect of Ex-vivo Expanded Umbilical Cord Blood Regulatory T Cells With Liraglutide on Autoimmune Diabetes
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Type1 Diabetes Mellitus
Autoimmune Diabetes
Keywords: Autoimmune Diabetes
Umbilical Cord Blood Regulatory T Lymphocyte
Liraglutide
Lead sponsor: Second Xiangya Hospital of Central South University
Sponsor class: OTHER
First posted: 2017-01-05
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Adverse effects
timeFrame: 2 years
Secondary outcomes:
measure: Change in HbA1C
timeFrame: 2 years
measure: Change in C-peptide
timeFrame: 2 years
measure: Change in insulin dose
timeFrame: 2 years
measure: Hypoglycaemic events
timeFrame: 2 years
measure: Change in titer of autoantibodies
timeFrame: 2 years
measure: Change in immune cells diversities and quantities.
timeFrame: 2 years
measure: Change in autoimmune-related cytokines
timeFrame: 2 years
measure: Life quality evaluation
timeFrame: 2 years
Other outcomes:
Locations:
city: Changsha
country: China
facility: Institute of Metabolism and Endocrinology, Second Xiangya Hospital, Central South University
state: Hunan
Study officials:
affiliation: Second Xiangya Hospital
name: Zhiguang Zhou, MD/PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Second Xiangya Hospital
name: Haibo Yu, MD/PhD
role: PRINCIPAL_INVESTIGATOR
References:
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citation: Brunstein CG, Miller JS, Cao Q, McKenna DH, Hippen KL, Curtsinger J, Defor T, Levine BL, June CH, Rubinstein P, McGlave PB, Blazar BR, Wagner JE. Infusion of ex vivo expanded T regulatory cells in adults transplanted with umbilical cord blood: safety profile and detection kinetics. Blood. 2011 Jan 20;117(3):1061-70. doi: 10.1182/blood-2010-07-293795. Epub 2010 Oct 15.
citation: Rondas D, D'Hertog W, Overbergh L, Mathieu C. Glucagon-like peptide-1: modulator of beta-cell dysfunction and death. Diabetes Obes Metab. 2013 Sep;15 Suppl 3:185-92. doi: 10.1111/dom.12165.
citation: Chang TJ, Tseng HC, Liu MW, Chang YC, Hsieh ML, Chuang LM. Glucagon-like peptide-1 prevents methylglyoxal-induced apoptosis of beta cells through improving mitochondrial function and suppressing prolonged AMPK activation. Sci Rep. 2016 Mar 21;6:23403. doi: 10.1038/srep23403.
citation: Zoso A, Serafini P, Lanzoni G, Peixoto E, Messinger S, Mantero A, Padilla-Tellez ND, Baidal DA, Alejandro R, Ricordi C, Inverardi L. G-CSF and Exenatide Might Be Associated with Increased Long-Term Survival of Allogeneic Pancreatic Islet Grafts. PLoS One. 2016 Jun 10;11(6):e0157245. doi: 10.1371/journal.pone.0157245. eCollection 2016.