Clinical trial NCT02932826: Safety Study and Therapeutic Effects of Umbilical Cord Blood Treg on Autoimmune Diabetes
Official title: Phase 1/ Phase 2 Study of the Therapeutic Effect of Ex-vivo Expanded Umbilical Cord Blood Regulatory T Cells on Autoimmune Diabetes
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Diabetes Mellitus, Type 1
Keywords: Autoimmune Diabetes
Umbilical Cord Blood Cell
Regulatory T Lymphocyte
Cell Therapy
Lead sponsor: Second Xiangya Hospital of Central South University
Sponsor class: OTHER
First posted: 2016-10-13
Enrollment: 40
Sex: ALL
Minimum age (years): 6
Maximum age (years): 60
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Number of Participants with Adverse events as a Measure of Safety and Tolerability
timeFrame: 2 years
Secondary outcomes:
measure: C-peptide
timeFrame: 2 years
measure: Insulin requirement
timeFrame: 2 years
measure: Blood glucose
timeFrame: 2 years
measure: HbA1c
timeFrame: 2 years
measure: Autoimmune Status
timeFrame: 2 years
Other outcomes:
Locations:
city: Changsha
country: China
facility: Institute of Metabolism and Endocrinology, Second Xiangya Hospital, Central South University
state: Hunan
Study officials:
affiliation: Second Xiangya Hospital of Central South University
name: Zhiguang Zhou, MD/PhD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
citation: 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.