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

NCT ID: NCT02932826

Last Updated: 2023-03-14

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-10-31
• Study Completion Date: 2025-11-30

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.

Conditions

Diabetes Mellitus, Type 1

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

Group Type: EXPERIMENTAL

Umbilical Cord Blood Regulatory T cells Therapy

Intervention Type: BIOLOGICAL

Receive Treg infusion: 1\~5\*10\^6/kg b.w. in 100ml NS

Insulin

Intervention Type: DRUG

Treated according to routine clinical practice at the discretion of the treating physician

Insulin

subjects will be treated with insulin according to routine clinical practice at the discretion of the treating physician

Group Type: ACTIVE_COMPARATOR

Insulin

Intervention Type: DRUG

Treated according to routine clinical practice at the discretion of the treating physician

Interventions

Umbilical Cord Blood Regulatory T cells Therapy

Receive Treg infusion: 1\~5\*10\^6/kg b.w. in 100ml NS

Intervention Type: BIOLOGICAL

Insulin

Treated according to routine clinical practice at the discretion of the treating physician

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 6 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Second Xiangya Hospital of Central South University

OTHER

Sponsor Role: lead

Responsible Party

Zhiguang Zhou

MD/PhD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Zhiguang Zhou, MD/PhD

Role: PRINCIPAL_INVESTIGATOR

Second Xiangya Hospital of Central South University

Locations

Institute of Metabolism and Endocrinology, Second Xiangya Hospital, Central South University

Changsha, Hunan, China

Site Status: RECRUITING

Countries

China

Central Contacts

Zhiguang Zhou, MD/PhD

Role: CONTACT

zhouzg@hotmail.com

+86-731-85292154

Facility Contacts

Zhiguang Zhou, MD/PhD

Role: primary

zhouzg@hotmail.com

86-731-85292154

References

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.

Reference Type: BACKGROUND

PMID: 23263503 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 22348606 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 20952687 (View on PubMed)

Other Identifiers

2015CX009

Identifier Type: -

Identifier Source: org_study_id