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

Primary Purpose

Diabetes Mellitus, Type 1

Status

Recruiting

Phase

Phase 1

Locations

China

Study Type

Interventional

Intervention

Umbilical Cord Blood Regulatory T cells Therapy

Insulin

About this trial

This is an interventional treatment trial for Diabetes Mellitus, Type 1 focused on measuring Autoimmune Diabetes, Umbilical Cord Blood Cell, Regulatory T Lymphocyte, Cell Therapy

Eligibility Criteria

6 Years - 60 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

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

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Treg Treatment + Insulin

Insulin

Arm Description

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

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

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

C-peptide

Measure the C-peptide level of participant after treatment

Insulin requirement

Measure the Insulin requirement of participant after treatment

Blood glucose

Measure the blood glucose level of participant after treatment

HbA1c

Measure the HbA1C level of participant after treatment

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.

Full Information

NCT ID

NCT02932826

First Posted

October 11, 2016

Last Updated

March 13, 2023

Sponsor

Second Xiangya Hospital of Central South University

1. Study Identification

Unique Protocol Identification Number

NCT02932826

Brief Title

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

2. Study Status

Record Verification Date

March 2023

Overall Recruitment Status

Recruiting

Study Start Date

October 2016 (undefined)

Primary Completion Date

June 2025 (Anticipated)

Study Completion Date

November 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Second Xiangya Hospital of Central South University

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Diabetes Mellitus, Type 1

Keywords

Autoimmune Diabetes, Umbilical Cord Blood Cell, Regulatory T Lymphocyte, Cell Therapy

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

40 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Treg Treatment + Insulin

Arm Type

Experimental

Arm Description

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

Arm Title

Insulin

Arm Type

Active Comparator

Arm Description

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

Intervention Type

Biological

Intervention Name(s)

Umbilical Cord Blood Regulatory T cells Therapy

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Insulin

Intervention Description

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

Primary Outcome Measure Information:

Title

Number of Participants with Adverse events as a Measure of Safety and Tolerability

Description

Time Frame

2 years

Secondary Outcome Measure Information:

Title

C-peptide

Description

Measure the C-peptide level of participant after treatment

Time Frame

2 years

Title

Insulin requirement

Description

Measure the Insulin requirement of participant after treatment

Time Frame

2 years

Title

Blood glucose

Description

Measure the blood glucose level of participant after treatment

Time Frame

2 years

Title

HbA1c

Description

Measure the HbA1C level of participant after treatment

Time Frame

2 years

Title

Autoimmune Status

Description

Time Frame

2 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

6 Years

Maximum Age & Unit of Time

60 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Zhiguang Zhou, MD/PhD

Phone

+86-731-85292154

zhouzg@hotmail.com

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Zhiguang Zhou, MD/PhD

Organizational Affiliation

Second Xiangya Hospital of Central South University

Official's Role

Principal Investigator

Facility Information:

Facility Name

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

City

Changsha

State/Province

Hunan

ZIP/Postal Code

410011

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Zhiguang Zhou, MD/PhD

Phone

86-731-85292154

zhouzg@hotmail.com

12. IPD Sharing Statement

Citations:

PubMed Identifier

23263503

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.

Results Reference

background

PubMed Identifier

22348606

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.

Results Reference

background

PubMed Identifier

20952687

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.

Results Reference

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

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