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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 : January 6, 2017
Sponsor:
Information provided by (Responsible Party):

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

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 : January 2019
Estimated Study Completion Date : November 2019

Resource links provided by the National Library of Medicine

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 :
  1. 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 :
  1. Change in HbA1C [ Time Frame: 2 years ]
  2. Change in C-peptide [ Time Frame: 2 years ]
  3. Change in insulin dose [ Time Frame: 2 years ]
  4. Hypoglycaemic events [ Time Frame: 2 years ]
  5. Change in titer of autoantibodies [ Time Frame: 2 years ]
  6. Change in immune cells diversities and quantities. [ Time Frame: 2 years ]
  7. Change in autoimmune-related cytokines [ Time Frame: 2 years ]
  8. Life quality evaluation [ Time Frame: 2 years ]
    Number of participants with disturbance of emotion, sleep, resting or energy.


Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
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
Contact: Zhiguang Zhou, MD/PhD 86-731-85292154 zhouzg@hotmail.com

Locations
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
More Information

Publications:

Responsible Party: Zhiguang Zhou, Principal Investigator, Second Xiangya Hospital of Central South University
ClinicalTrials.gov Identifier: NCT03011021     History of Changes
Other Study ID Numbers: 0001
First Posted: January 5, 2017    Key Record Dates
Last Update Posted: January 6, 2017
Last Verified: January 2017

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