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

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ClinicalTrials.gov Identifier: NCT03011021

Recruitment Status : Recruiting

First Posted : January 5, 2017

Last Update Posted : March 14, 2023

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Sponsor:

Information provided by (Responsible Party):

Zhiguang Zhou, Second Xiangya Hospital of Central South University

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Type1 Diabetes Mellitus Autoimmune Diabetes	Drug: Liraglutide Biological: UCB-Treg Drug: Insulin	Phase 1 Phase 2

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.

Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	40 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
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 Start Date :	January 2017
Estimated Primary Completion Date :	June 2025
Estimated Study Completion Date :	June 2025

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: Type 1 diabetes

Drug Information available for: Liraglutide

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
Experimental: 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.	Drug: Liraglutide Dose escalation of Liraglutide starts from 0.6 mg up to 1.2 mg per day. Biological: UCB-Treg Receive Treg infusion: 1~5*10^6/kg b.w. in 100ml normal saline Drug: Insulin Receive insulin following clinician's instruction.
Active Comparator: 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.	Biological: UCB-Treg Receive Treg infusion: 1~5*10^6/kg b.w. in 100ml normal saline Drug: Insulin Receive insulin following clinician's instruction.
Active Comparator: 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.	Drug: Liraglutide Dose escalation of Liraglutide starts from 0.6 mg up to 1.2 mg per day. Drug: Insulin Receive insulin following clinician's instruction.
Active Comparator: Insulin Patients will receive insulin injection as a routine therapy.	Drug: Insulin Receive insulin following clinician's instruction.

Outcome Measures

Primary Outcome Measures :

Adverse effects [ Time Frame: 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 :

Change in HbA1C [ Time Frame: 2 years ]
Measure the HbA1C level after treatment
Change in C-peptide [ Time Frame: 2 years ]
Measure the C-peptide level after treatment
Change in insulin dose [ Time Frame: 2 years ]
Measure insulin dose patient used after treatment
Hypoglycaemic events [ Time Frame: 2 years ]
Measure the number of participants with Hypoglycaemic events
Change in titer of autoantibodies [ Time Frame: 2 years ]
Measure the titer of antoantibodies of participant after treatment
Change in immune cells diversities and quantities. [ Time Frame: 2 years ]
Measure the immune cells diversities and quantities after treatment
Change in autoimmune-related cytokines [ Time Frame: 2 years ]
Measure the change of autoimmune- related cytokines after treatment
Life quality evaluation [ Time Frame: 2 years ]
Number of participants with disturbance of emotion, sleep, resting or energy.

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

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.

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03011021

Contacts

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Contact: Zhiguang Zhou, MD/PhD	86-731-85292154	zhouzg@hotmail.com

Locations

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China, Hunan
Institute of Metabolism and Endocrinology, Second Xiangya Hospital, Central South University	Recruiting
Changsha, Hunan, China, 410011
Contact: Zhiguang Zhou, MD/PhD 86-731-85292154 zhouzg@hotmail.com

Sponsors and Collaborators

Second Xiangya Hospital of Central South University

Investigators

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Principal Investigator:	Zhiguang Zhou, MD/PhD	Second Xiangya Hospital
Principal Investigator:	Haibo Yu, MD/PhD	Second Xiangya Hospital

More Information

Publications:

Milward K, Issa F, Hester J, Figueroa-Tentori D, Madrigal A, Wood KJ. Multiple unit pooled umbilical cord blood is a viable source of therapeutic regulatory T cells. Transplantation. 2013 Jan 15;95(1):85-93. doi: 10.1097/TP.0b013e31827722ed.

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.

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.

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.

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. Erratum In: Sci Rep. 2016 May 31;6:26917.

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.

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Responsible Party:	Zhiguang Zhou, Principal Investigator, Second Xiangya Hospital of Central South University
ClinicalTrials.gov Identifier:	NCT03011021
Other Study ID Numbers:	0001
First Posted:	January 5, 2017 Key Record Dates
Last Update Posted:	March 14, 2023
Last Verified:	March 2023

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Studies a U.S. FDA-regulated Drug Product:	No
Studies a U.S. FDA-regulated Device Product:	No

Keywords provided by Zhiguang Zhou, Second Xiangya Hospital of Central South University:


Autoimmune Diabetes Umbilical Cord Blood Regulatory T Lymphocyte Liraglutide

Additional relevant MeSH terms:

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Diabetes Mellitus Diabetes Mellitus, Type 1 Glucose Metabolism Disorders Metabolic Diseases Endocrine System Diseases Autoimmune Diseases Immune System Diseases	Liraglutide Hypoglycemic Agents Physiological Effects of Drugs Incretins Hormones Hormones, Hormone Substitutes, and Hormone Antagonists

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