T2D
Conditions
Keywords
type 2 diabetes, Bone-marrow mononuclear cells, Umbilical cord mesenchymal stem cells, Glycemic control
Brief summary
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
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.
Interventions
BIOLOGICALBone-marrow aspiration, Intra-pancreatic Catheterisation of BM-MNC
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
BIOLOGICALIntravenous Infusion of UC-MSC
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
Sponsors
Dr Cipto Mangunkusumo General Hospital
Indonesia University
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
5 subjects receive BM-MNC and 10 subjects receive UC-MSC
Eligibility
Sex/Gender
ALL
Age
30 Years to 65 Years
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Decreasing total daily dose of insulin (>= 30%) | Before intervention, 1st, 3rd, 6th, and 12th month after intervention | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Increasing of C-peptide level | Before intervention, 1st, 3rd, 6th, and 12th month after intervention | Measurements were obtained with mixed meal tolerance test |
| Decreasing of insulin resistance level | Before intervention, 1st, 3rd, 6th, and 12th month after intervention | Measurement of HOMA-IR, calculated using fasting C-peptide and fasting plasma glucose formula |
| Immunology/inflammatory markers | Before intervention, 1st, 3rd, 6th, and 12th month after intervention | Measurements of Interleukin-10 and TNF-alfa from serum and supernatant from PBMC stimulation |
| Adverse events | Up to 12 months after intervention | Thrombosis, hemorrhage, and infection |
| HbA1c | Before intervention, 1st, 3rd, 6th, and 12th month after intervention | Stable HbA1c or decreasing HbA1c (from baseline) |
Countries
Indonesia
Outcome results
None listed