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

Diabetes Mellitus, Type 1 Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02932826
• Other study ID #: 2015CX009
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: October 2016
• Est. completion date: November 2025

Study information

• Verified date: March 2023
• Source: Second Xiangya Hospital of Central South University
• Contact: Zhiguang Zhou, MD/PhD
• Phone: +86-731-85292154
• Email: zhouzg[@]hotmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: November 2025
• Est. primary completion date: June 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Years to 60 Years

Eligibility

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

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 1

Intervention

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

Locations

Country	Name	City	State
China	Institute of Metabolism and Endocrinology, Second Xiangya Hospital, Central South University	Changsha	Hunan

Sponsors (1)

Lead Sponsor	Collaborator
Second Xiangya Hospital of Central South University

Country where clinical trial is conducted

China, 

References & Publications (3)

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	C-peptide	Measure the C-peptide level of participant after treatment	2 years
Secondary	Insulin requirement	Measure the Insulin requirement of participant after treatment	2 years
Secondary	Blood glucose	Measure the blood glucose level of participant after treatment	2 years
Secondary	HbA1c	Measure the HbA1C level of participant after treatment	2 years
Secondary	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