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

NCT03011021 | Unknown Phase 1

• 1 other identifier: 0001
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

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.

Conditions

Type1 Diabetes Mellitus; Autoimmune Diabetes

Keywords

Autoimmune Diabetes; Umbilical Cord Blood Regulatory T Lymphocyte; Liraglutide

Outcome Measures

Primary Outcomes (1)

• Adverse effects

  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.

  2 years

Secondary Outcomes (8)

• Change in HbA1C

  2 years

• Change in C-peptide

  2 years

• Change in insulin dose

  2 years

• Hypoglycaemic events

  2 years

• Change in titer of autoantibodies

  2 years

Study Arms (4)

UCB-Treg plus Liraglutide

EXPERIMENTAL

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; Biological: UCB-Treg; Drug: Insulin

UCB-Treg

ACTIVE COMPARATOR

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; Drug: Insulin

Liraglutide

ACTIVE COMPARATOR

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; Drug: Insulin

Insulin

ACTIVE COMPARATOR

Patients will receive insulin injection as a routine therapy.

Drug: Insulin

Interventions

Liraglutide DRUG

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

Liraglutide; UCB-Treg plus Liraglutide

UCB-Treg BIOLOGICAL

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

UCB-Treg; UCB-Treg plus Liraglutide

Insulin DRUG

Receive insulin following clinician's instruction.

Insulin; Liraglutide; UCB-Treg; UCB-Treg plus Liraglutide

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Second Xiangya Hospital of Central South University: lead

Study Sites (1)

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

Changsha, Hunan, 410011, China

RECRUITING

Related Publications (6)

• 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.

  PMID: 23263503 BACKGROUND

• 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.

  PMID: 22348606 BACKGROUND

• 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.

  PMID: 20952687 BACKGROUND

• 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.

  PMID: 24003936 BACKGROUND

• 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.

  PMID: 26997114 BACKGROUND

• 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.

  PMID: 27285580 BACKGROUND

MeSH Terms

Conditions

Diabetes Mellitus, Type 1

Interventions

Liraglutide; Insulin

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Glucagon-Like Peptide 1; Glucagon-Like Peptides; Proglucagon; Gastrointestinal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Proinsulin; Insulins; Pancreatic Hormones; Peptide Hormones; Peptides; Amino Acids, Peptides, and Proteins

Study Officials

• Zhiguang Zhou, MD/PhD

  Second Xiangya Hospital

  PRINCIPAL INVESTIGATOR

• Haibo Yu, MD/PhD

  Second Xiangya Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Zhiguang Zhou, MD/PhD

CONTACT

86-731-85292154; zhouzg@hotmail.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: January 2, 2017
• First Posted: January 5, 2017
• Study Start: January 1, 2017
• Primary Completion: June 1, 2025
• Study Completion: June 1, 2025
• Last Updated: March 14, 2023

Record last verified: 2023-03

Locations

CN (1)