Safety and Efficacy of Umbilical Cord Blood Regulatory T Cells Plus Liraglutide on Autoimmune Diabetes

NCT ID: NCT03011021

Last Updated: 2023-03-14

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-01-31
• Study Completion Date: 2025-06-30

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.

Conditions

Type1 Diabetes Mellitus; Autoimmune Diabetes

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Liraglutide

Intervention Type: DRUG

Dose escalation of Liraglutide starts from 0.6 mg up to 1.2 mg per day.

UCB-Treg

Intervention Type: BIOLOGICAL

Receive Treg infusion: 1\~5\*10\^6/kg b.w. in 100ml normal saline

Insulin

Intervention Type: DRUG

Receive insulin following clinician's instruction.

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.

Group Type: ACTIVE_COMPARATOR

UCB-Treg

Intervention Type: BIOLOGICAL

Receive Treg infusion: 1\~5\*10\^6/kg b.w. in 100ml normal saline

Insulin

Intervention Type: DRUG

Receive insulin following clinician's instruction.

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.

Group Type: ACTIVE_COMPARATOR

Liraglutide

Intervention Type: DRUG

Dose escalation of Liraglutide starts from 0.6 mg up to 1.2 mg per day.

Insulin

Intervention Type: DRUG

Receive insulin following clinician's instruction.

Insulin

Patients will receive insulin injection as a routine therapy.

Group Type: ACTIVE_COMPARATOR

Insulin

Intervention Type: DRUG

Receive insulin following clinician's instruction.

Interventions

Liraglutide

Dose escalation of Liraglutide starts from 0.6 mg up to 1.2 mg per day.

Intervention Type: DRUG

UCB-Treg

Receive Treg infusion: 1\~5\*10\^6/kg b.w. in 100ml normal saline

Intervention Type: BIOLOGICAL

Insulin

Receive insulin following clinician's instruction.

Intervention Type: DRUG

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Second Xiangya Hospital of Central South University

OTHER

Sponsor Role: lead

Responsible Party

Zhiguang Zhou

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Zhiguang Zhou, MD/PhD

Role: PRINCIPAL_INVESTIGATOR

Second Xiangya Hospital

Haibo Yu, MD/PhD

Role: PRINCIPAL_INVESTIGATOR

Second Xiangya Hospital

Locations

Institute of Metabolism and Endocrinology, Second Xiangya Hospital, Central South University

Changsha, Hunan, China

Site Status: RECRUITING

Countries

China

Central Contacts

Zhiguang Zhou, MD/PhD

Role: CONTACT

zhouzg@hotmail.com

86-731-85292154

Facility Contacts

Zhiguang Zhou, MD/PhD

Role: primary

zhouzg@hotmail.com

86-731-85292154

References

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Reference Type: BACKGROUND

PMID: 23263503 (View on PubMed)

Fan H, Yang J, Hao J, Ren Y, Chen L, Li G, Xie R, Yang Y, Gao F, Liu M. Comparative study of regulatory T cells expanded ex vivo from cord blood and adult peripheral blood. Immunology. 2012 Jun;136(2):218-30. doi: 10.1111/j.1365-2567.2012.03573.x.

Reference Type: BACKGROUND

PMID: 22348606 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 20952687 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 24003936 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 26997114 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 27285580 (View on PubMed)

Other Identifiers

0001

Identifier Type: -

Identifier Source: org_study_id