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

Phase 1

Recruiting

• Conditions: Diabetes Mellitus, Type 1
• Interventions: Biological: Umbilical Cord Blood Regulatory T cells Therapy; Drug: Insulin

• Registration Number: NCT02932826
• Lead Sponsor: Second Xiangya Hospital of Central South University

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 on autoimmune diabetes.

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 Timeline

• Study Start: 2016-10
• Study First Submitted: 2016-10-11
• Study First Submitted QC: 2016-10-11
• Study First Posted: 2016-10-13
• Status Verified: 2023-03
• Last Update Submitted: 2023-03-13
• Last Update Posted: 2023-03-14
• Primary Completion: 2025-06
• Study Completion: 2025-11

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 40

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Treg Treatment + Insulin	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
Treg Treatment + Insulin	Umbilical Cord Blood Regulatory T cells Therapy	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
Insulin	Insulin	subjects will be treated with insulin according to routine clinical practice at the discretion of the treating physician

Primary Outcome Measures

Name	Time	Method
Number of Participants with Adverse events as a Measure of Safety and Tolerability	2 years	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

Name	Time	Method
C-peptide	2 years	Measure the C-peptide level of participant after treatment
Autoimmune Status	2 years	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.
Insulin requirement	2 years	Measure the Insulin requirement of participant after treatment
HbA1c	2 years	Measure the HbA1C level of participant after treatment
Blood glucose	2 years	Measure the blood glucose level of participant after treatment

Trial Locations

Locations (1)

Institute of Metabolism and Endocrinology, Second Xiangya Hospital, Central South University; 🇨🇳 Changsha, Hunan, China