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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Diabetes Mellitus, Type 1

Intervention / Treatment
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* Biological: Umbilical Cord Blood Regulatory T cells Therapy
* Drug: Insulin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 Diagnosis of Autoimmune Diabetes within 3 years of screening Between 6 to 60 years of age Positive for at least one of the anti-islet autoantibodies: GADA, IA2A, ZnT8A Fasting or postprandial plasma C-peptide more than 200 pmol/L Written informed consent from the patient or the patient's parents for patients under the age of 18 years Exclusion Criteria: Any clinically significant diseases in liver (ALT and AST over 2 times upper normal limit), kidney (Scr over 133umol/L), and heart Presence of anemia (Hb ≤100g/L), leukopenia (<3.5×10^9/L) Presence of disorder in coagulation or anticoagulation, or thrombocytopenia (platelets <100×10^9/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 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 afer recruitment 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 Presence of diabetic microvascular or macrovascular diseases Presence of hypertension Any medical condition that, in the opinion of the investigator, will interfere with safe participation in the trial

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treg Treatment + Insulin<br>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<br>* Receive Treg infusion: 1 5*10^6/kg b.w. in 100ml NS<br>Drug: Insulin<br>* Treated according to routine clinical practice at the discretion of the treating physician<br>|
| Active Comparator: Insulin<br>subjects will be treated with insulin according to routine clinical practice at the discretion of the treating physician | Drug: Insulin<br>* Treated according to routine clinical practice at the discretion of the treating physician<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Autoimmune Diabetes, Umbilical Cord Blood Cell, Regulatory T Lymphocyte, Cell Therapy