Safety and Efficacy Study of Umbilical Cord/Placenta-Derived Mesenchymal Stem Cells to Treat Type 2 Diabetes

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety and efficacy of mesenchymal stem cells (MSCs) derived from human umbilical cord/placenta at a dose of 1.0E+6 MSC/kg for type 2 diabetes.

Detailed Description
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1. Intervention Details: Biological: umbilical cord/placenta-derived mesenchymal stem cells; Drug: 1. Oral Hypoglycemic Drugs, such as Dimethylbiguanide, Glurenorm and Acarbose, et al. 2. Insulins. 1st transplantation: after finishing all required examines according to protocol in Day 0, umbilical cord/placenta-derived MSCs are transplanted intravenously. 2nd transplantation: after finishing all required examines in Day 90, umbilical cord/placenta-derived-MSCs are transplanted intravenously if the effects of MSC are better than that before. At the same time, patients continue taking the oral hypoglycemic drugs, insulins or the combination of the oral hypoglycemic drugs and insulins which the patients have taken for controlling the higher blood sugar from Day 0 for 1 year. But the dose of the oral hypoglycemic drugs and insulins should be regulated according to the level of blood sugar. 2. Detailed Description: To evaluate the feasibility and safety of transplantation treatment using umbilical cord/placenta-derived mesenchymal stem cells in patients with type 2 diabetes mellitus undergoing the oral hypoglycemic drugs, insulins or the combination of the oral hypoglycemic drugs and insulins. To assess efficacy of transplantation treatment using umbilical cord/placenta-derived mesenchymal stem cells in patients with type 2 diabetes mellitus undergoing the oral hypoglycemic drugs, insulins or the combination of the oral hypoglycemic drugs and insulins. This study will last 2 to 3 years. Participants will be randomly assigned to receive either MSC transplant and the oral hypoglycemic drugs or MSC transplant and insulins or MSC transplant and the combination of the oral hypoglycemic drugs and insulins (experimental group) or the oral hypoglycemic drugs or insulins or the combination of the oral hypoglycemic drugs and insulins (control group). Patients will undergo MSC transplant at the start of the study on Day 0 and take the oral hypoglycemic drugs, insulins or the combination of the oral hypoglycemic drugs and insulins for 1 year. As control, some patients take the oral hypoglycemic drugs, insulins or the combination of the oral hypoglycemic drugs and insulins for 1 year. At the same time, the dose of the oral hypoglycemic drugs and insulins should be regulated according to the level of blood sugar. After 3 months, patients will receive the second MSC transplantation. After six and twelve months from the first transplantation, patients will be evaluated.

Official Title
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Safety/Efficacy Assessed Study on Transplantation Therapy Using Human Umbilical Cord/Placenta-derived Mesenchymal Stem Cells for Type 2 Diabetes Mellitus

Conditions
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Type 2 Diabetes

Intervention / Treatment
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* Biological: MSC


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Free will taking part in the study and ability to provide written informed consent Type 2 diabetes mellitus (as guideline WHO, 1999) Age 18-80 years old, Male/Female 19≤Body mass index (BMI)≤30㎏/㎡ Fast blood glucose (FBG)≥7.0 mmol/L, and HbAc1≥7％ Intravenous insulin tolerance test（ITT）indicate patient being insulin resistance Not pregnant or nursing No moderate or sever organ dysfunction: Ejection fraction>45%; Creatinine <176 mmol/L No active severe viral or fungus infection Exclusion Criteria: Severe concurrent medical condition (e.g., serious heart disease, lung disease, or hematopoietic dysfunction, or liver dysfunction, or kidney dysfunction) Active infection requiring treatment Unexplained febrile illness Known immunosuppressive disease, e.g. HIV infection, or hepatitis B or C infection Psychiatric condition that would limit informed consent Patient has enrolled another clinical trial study within last 4 weeks.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MSC and the oral hypoglycemic drugs<br>1.0E+6 MSC/kg, IV drop and repeat to apply in Day 90 if the effect of MSC is better. At the same time, patient continues to apply the former oral hypoglycemic drugs, such as Dimethylbiguanide, Glurenorm and Acarbose, et al. and regulates the dosage for 1 year. | Biological: MSC<br>* 1.0E+6 MSC/kg, IV drop in Day 0 and repeat to apply in Day 90 if the effect of MSC is better.<br>|
| Experimental: MSC and insulins<br>1.0E+6 MSC/kg, IV drop and repeat to apply in Day 90 if the effect of MSC is better. At the same time, patient continues to apply the former insulins and regulates the dosage for 1 year. | Biological: MSC<br>* 1.0E+6 MSC/kg, IV drop in Day 0 and repeat to apply in Day 90 if the effect of MSC is better.<br>|
| Experimental: MSC and the combination of drugs and insulins<br>1.0E+6 MSC/kg, IV drop and repeat to apply in Day 90 if the effect of MSC is better. At the same time, patient continues to apply the former combination of the oral hypoglycemic drugs and insulins and regulates the dosage for 1 year. | Biological: MSC<br>* 1.0E+6 MSC/kg, IV drop in Day 0 and repeat to apply in Day 90 if the effect of MSC is better.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess efficacy of transplantation treatment using umbilical cord/placenta-derived mesenchymal stem cells in patients with type 2 diabetes mellitus | To assess efficacy of MSC through comparing the change of ITT, Hemoglobin A1c, FBG, PBG, C-peptide levels and T cell subsets with that of baseline. The change of insulin resistance index(ITT) compared with baseline. Rate of reducing exogenous insulin requirement compared with baseline. The change of Fast blood glucose (FBG) and Postmeal blood glucose (PBG) compared with baseline. A reduction of ≥1% in HbA1c compared with baseline. The change of C-peptide levels compared with baseline. The change of T cell subsets compared with baseline. | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the incidence and severity of adverse events of transplantation treatment using umbilical cord/placenta-derived mesenchymal stem cells in patients with type 2 diabetes mellitus | To evaluate if there have occured the adverse everts such as fever, allergy, et al. and their severity. | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diabetes, Diabetes Medicines: Oral Hypoglycemic Drugs and Insulins., Umbilical Cord/placenta-Derived MSC, Transplantation