Safety Study and Therapeutic Effects of Umbilical Cord Blood Treg on Autoimmune Diabetes

Phase 1/ Phase 2 Study of the Therapeutic Effect of Ex-vivo Expanded Umbilical Cord Blood Regulatory T Cells on Autoimmune Diabetes

The purpose of this study is to investigate the safety and therapeutic effect of ex-vivo expanded umbilical cord blood regulatory T cells on autoimmune diabetes.

Study Overview

• Status: Recruiting
• Conditions: Diabetes Mellitus, Type 1
• Intervention / Treatment: Biological: Umbilical Cord Blood Regulatory T cells Therapy; Drug: Insulin

Detailed Description

The regulatory T cells (Treg) used in this study will be produced from human umbilical cord blood. The umbilical cord blood will be freshly collected and immediately separated to buffy coat in a GMP laboratory, thus to be further sorted into Treg and other subsets. Then the Treg will be expanded ex-vivo for approximately 14 days until tested for its surface markers and suppressive ability. During the time of ex-vivo expansion, eligible autoimmune diabetes patients will be recruited and admitted to our hospital in order to go through required examinations. Once the Treg product has reached the safety and efficacy standards, the patient will receive the Treg product infusion under close surveillance of doctors and then go through regular follow-ups to investigate the safety and therapeutic effect of the Treg product on autoimmune diabetes patients.

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Zhiguang Zhou, MD/PhD; Phone Number: +86-731-85292154; Email: zhouzg@hotmail.com

Study Locations

• China
  • Hunan
    • Changsha, Hunan, China, 410011
      • Recruiting
      • Institute of Metabolism and Endocrinology, Second Xiangya Hospital, Central South University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 60 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Autoimmune diabetes patients are screened for enrollment in the study if both clinical signs and laboratory tests meet the diagnosis standards of American Diabetes Association
2. Diagnosis of Autoimmune Diabetes within 3 years of screening
3. Between 6 to 60 years of age
4. Positive for at least one of the anti-islet autoantibodies: GADA, IA2A, ZnT8A
5. Fasting or postprandial plasma C-peptide more than 200 pmol/L
6. Written informed consent from the patient or the patient's parents for patients under the age of 18 years

Exclusion Criteria:

1. Any clinically significant diseases in liver (ALT and AST over 2 times upper normal limit), kidney (Scr over 133umol/L), and heart
2. Presence of anemia (Hb ≤100g/L), leukopenia (<3.5×10^9/L)
3. Presence of disorder in coagulation or anticoagulation, or thrombocytopenia (platelets <100×10^9/L)
4. 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
5. Presence of any kind of chronic infection or immune deficiency, including hepatitis B, hepatitis C, HIV, syphilis or tuberculosis
6. Chronic use of systemic glucocorticoids or other immunosuppressive agents for over 3 months
7. Any history of malignancy
8. Female patients who are pregnant or breastfeeding; any female who is unwilling to use a reliable and effective form of contraception for 2 years afer recruitment
9. Presence of any infectious diseases, including active skin infections, flu, fever, upper or lower respiratory track 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
10. Presence of diabetic microvascular or macrovascular diseases
11. Presence of hypertension
12. Any medical condition that, in the opinion of the investigator, will interfere with safe participation in the trial

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treg Treatment + Insulin; subjects will be treated with Umbilical Cord Blood Regulatory T cells Therapy and insulin according to routine clinical practice at the discretion of the treating physician	Biological: Umbilical Cord Blood Regulatory T cells Therapy; Receive Treg infusion: 1~5*10^6/kg b.w. in 100ml NS; Drug: Insulin; Treated according to routine clinical practice at the discretion of the treating physician
Active Comparator: Insulin; subjects will be treated with insulin according to routine clinical practice at the discretion of the treating physician	Drug: Insulin; Treated according to routine clinical practice at the discretion of the treating physician

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with Adverse events as a Measure of Safety and Tolerability	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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
C-peptide	Measure the C-peptide level of participant after treatment	2 years
Insulin requirement	Measure the Insulin requirement of participant after treatment	2 years
Blood glucose	Measure the blood glucose level of participant after treatment	2 years
HbA1c	Measure the HbA1C level of participant after treatment	2 years
Autoimmune Status	The autoimmune status refers to the state and degree of autoimmune attacks in autoimmune diabetes patients. Measures include change in titer of autoantibodies, change in subsets of immune cells, and change in autoimmune related cytokines.	2 years

Collaborators and Investigators

• Sponsor: Second Xiangya Hospital of Central South University

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start: October 1, 2016
• Primary Completion (Anticipated): June 1, 2025
• Study Completion (Anticipated): November 1, 2025

Study Registration Dates

• First Submitted: October 11, 2016
• First Submitted That Met QC Criteria: October 11, 2016
• First Posted (Estimate): October 13, 2016

Study Record Updates

• Last Update Posted (Actual): March 14, 2023
• Last Update Submitted That Met QC Criteria: March 13, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: Cell Therapy; Autoimmune Diabetes; Umbilical Cord Blood Cell; Regulatory T Lymphocyte
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1; Hypoglycemic Agents; Physiological Effects of Drugs; Insulin
• Other Study ID Numbers: 2015CX009

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No