BM-MNC and UCMSC for Type 2 Diabetes Mellitus Patients

Study Overview
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Brief Summary
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The aim of this preliminary study is to evaluate the safety and efficacy of bone-marrow mononuclear cells (BM-MNCs) and umbilical-cord tissue-derived mesenchymal stem cells (UC-MSCs) administration in type 2 diabetes patients

Detailed Description
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Type 2 diabetes (T2D) patients had peripheral insulin resistance accompanied by progressive pancreatic beta cell degeneration and dysfunction due to glucotoxicity and lipotoxicity. Several studies have shown that the immune system plays a significant role in the pathogenesis of T2D. Bone-marrow mononuclear cells (BM-MNCs) and umbilical-cord tissue-derived mesenchymal stem cells (UC-MSCs) via its immunomodulatory properties have the potential to improve insulin resistance condition and pancreatic beta-cells dysfunction thus improve the glycemic control and insulin requirement in T2D patients. In this pilot study, we plan to recruit 15 T2D patients with total daily dose of insulin >= 0.5 unit/kgBW/day to receive BM-MNCs (5 subjects) or UC-MSCs injections (10 subjects). These subjects will be closely followed up for 12 months for evaluation of primary and secondary outcome.

Official Title
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Effectivity and Safety of Autologous BM-MNC Stem Cell Therapy and Allogenic Umbilical Cord Mesenchymal Stem Cell for Type 2 Diabetes Mellitus Patients

Conditions
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T2D

Intervention / Treatment
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* Biological: Bone-marrow aspiration, Intra-pancreatic Catheterisation of BM-MNC
* Biological: Intravenous Infusion of UC-MSC


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Type 2 diabetes patients on insulin therapy with or without oral hypoglycemic agents, with total daily dose of insulin >= 0,5 unit/kg body weight Stable HbA1C in the last six months (HbA1c <= 8.5%) Exclusion Criteria: Type 1 diabetes mellitus eGFR < 45 mL/min/m2 (for BM-MNC) Liver disease (moderate- severe) Active infection Contrast hypersensitivity (for BM-MNC) History of Malignancy Acute coronary syndrome in last three months Coronary arterial diseases with significant stenosis and has not carried out revascularization Pregnancy (for women subjects)

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: 5 subjects receive BM-MNC and 10 subjects receive UC-MSC
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BM-MNC experimental<br>Autologue bone marrow mononuclear cell | Biological: Bone-marrow aspiration, Intra-pancreatic Catheterisation of BM-MNC<br>* Autologous bone-marrow mononuclear cells infused to the main blood vessels that supply the pancreas according to the results of previous pancreatic CT-scan, performed by interventional radiologist. The target is to distribute the BM-MNCs equally in all part of the pancreas. Dosage: 1 x 10^5 - 1 x 10^6 CD34 cells/kgBW<br>|
| Experimental: UC-MSC<br>Umbilical cord mesenchymal stem cell | Biological: Intravenous Infusion of UC-MSC<br>* Allogeneic umbilical cord tissue-derived mesenchymal stem cells will be given via intravenous infusion. Dosage: 2 x 10^6 cells/kgBW, twice, with three months interval<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Decreasing total daily dose of insulin (>= 30%) | After intervention, blood glucose level will be reported by the subjects on weekly basis. The insulin dose and/or oral medication will be adjusted accordingly. | Before intervention, 1st, 3rd, 6th, and 12th month after intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Increasing of C-peptide level | Measurements were obtained with mixed meal tolerance test | Before intervention, 1st, 3rd, 6th, and 12th month after intervention | 
| Decreasing of insulin resistance level | Measurement of HOMA-IR, calculated using fasting C-peptide and fasting plasma glucose formula | Before intervention, 1st, 3rd, 6th, and 12th month after intervention | 
| Immunology/inflammatory markers | Measurements of Interleukin-10 and TNF-alfa from serum and supernatant from PBMC stimulation | Before intervention, 1st, 3rd, 6th, and 12th month after intervention | 
| Adverse events | Thrombosis, hemorrhage, and infection | Up to 12 months after intervention | 
| HbA1c | Stable HbA1c or decreasing HbA1c (from baseline) | Before intervention, 1st, 3rd, 6th, and 12th month after intervention | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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type 2 diabetes, Bone-marrow mononuclear cells, Umbilical cord mesenchymal stem cells, Glycemic control