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The purpose of this study is to improve the blood glucose level in type 2 diabetic patients.
We hypothesize that Autologous bone marrow derived stem cells which would be expanded into culture and their subsequent transplant into the pancreas of patients with T2DM, aged 30 - 70 years with triple oral hypoglycemic agent failure and on insulin(>0.4 U/ kg body weight/day) will lead to abolition or reduction of insulin requirement by more than or equal to 50% in these patients over a period of 6 months. It is assumed that stem cell in these patients leads to increased angiogenesis, secretion of various cytokines and upregulation of pancreatic transcription factors and Vascular endothelial growth factor(VEGF) and creates a micro-environment which supports beta cell/resident stem cell activation and survival.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| mesenchymal stem cell transplantation | Experimental | Patients with Type 2 Diabetes mellitus on full doses of Vildagliptin+Pioglitazone+Metformin and requiring Insulin at dose of >0.4unit/Kg for blood glucose control. |
|
| Control | Sham Comparator | vildagliptin+metformin+pioglitazone and on Insulin >0.4unit/Kg who will act as active control.They will receive injectable placebo at Day 1 in addition to above and will be followed up for 6 months.Follow up investigation and Insulin dose titration will be similar to Group 1 |
|
| MNC's TRANSPLANTATION | Experimental | Patients with Type 2 Diabetes mellitus on full doses of Vildagliptin+Pioglitazone+Metformin and requiring Insulin at dose of >0.4unit/Kg for blood glucose control. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| mesenchymal stem cell transplantation | Biological | 20 - 30 ml of bone marrow will be aspirated and layered on density gradient medium (Ficoll - hypaque ) and stem cells will be separated. Separated mono nucleated cells will be dissolved in minimum essential medium and inoculated in culturing flask and mesenchymal will be allowed to adhere to culturing flask and mesenchymal stem cell will be injected into superior pancreatic duodenal artery . Patients will be urged to monitor and document blood glucose readings for next 6 months. Glucagon stimulated C - peptide HYPERGLYCEMIC CLAMP FOR ASSESSMENT OF BETA CELL FUNCTION , Homeostasis Model of Assessment - Insulin Resistance and Beta cell function ,HbA1c, lipid profile and biochemistry will be done at baseline and 6 months . |
| Measure | Description | Time Frame |
|---|---|---|
| Reduction of insulin requirement by ≥ 50% by the end of 6 months of autologous bone marrow derived stem cell transplantation and Improvement in Glucagon stimulated C - peptide levels and hyperglycemic clamp for assessment of beta cell function | 6 months |
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Inclusion Criteria:
Patients with type 2 diabetes mellitus between 30 and 70 years of age.
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| A Bhansali | Post Graduate Institute of Medical Education and Research, Chandigarh | Study Chair |
| V Jha | Post Graduate Institute of Medical Education and Research, Chandigarh | Principal Investigator |
| Neelam Marwaha | Post Graduate Institute of Medical Education and Research, Chandigarh | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Postgraduate Institute of Medical Education and Research | Chandigarh | Uttarakhand | 160012 | India |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 19686048 | Background | Bhansali A, Upreti V, Khandelwal N, Marwaha N, Gupta V, Sachdeva N, Sharma RR, Saluja K, Dutta P, Walia R, Minz R, Bhadada S, Das S, Ramakrishnan S. Efficacy of autologous bone marrow-derived stem cell transplantation in patients with type 2 diabetes mellitus. Stem Cells Dev. 2009 Dec;18(10):1407-16. doi: 10.1089/scd.2009.0164. | |
| 28690682 |
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| ID | Term |
|---|---|
| D003924 | Diabetes Mellitus, Type 2 |
| ID | Term |
|---|---|
| D003920 | Diabetes Mellitus |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
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| ID | Term |
|---|---|
| D045164 | Mesenchymal Stem Cell Transplantation |
| ID | Term |
|---|---|
| D033581 | Stem Cell Transplantation |
| D017690 | Cell Transplantation |
| D064987 | Cell- and Tissue-Based Therapy |
| D001691 | Biological Therapy |
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|
| control | Other | 5 ml of bone marrow will be aspirated and 3 mL of Vitamin B complex will be injected through transfemoral route into superior pancreatico-duodenal artery. Patients will be urged to monitor and document blood glucose readings for next 6 months. Glucagon stimulated C - peptide,HYPERGLYCEMIC CLAMP TO ASSESS BETA CELL FUNCTION. Homeostasis Model of Assessment - Insulin Resistance and Beta cell function ,HbA1c, lipid profile and biochemistry will be done at baseline and 6 months . |
|
| MNC's TRANSPLANTATION | Biological | 20 - 30 ml of bone marrow will be aspirated and layered on density gradient medium (Ficoll - hypaque ) and stem cells will be separated. Separated mono nucleated cells will injected into superior pancreatico duodenal artery. Patients will be urged to monitor and document blood glucose readings for next 6 months. Glucagon stimulated C - peptide HYPERGLYCEMIC CLAMP FOR ASSESSMENT OF BETA CELL FUNCTION , AND EUGLYCEMIC CLAMP TO ASSESS INSULIN SENSITIVITY .Homeostasis Model of Assessment - Insulin Resistance and Beta cell function ,HbA1c, lipid profile and biochemistry will be done at baseline and 6 months . |
|
| Bhansali S, Dutta P, Yadav MK, Jain A, Mudaliar S, Hawkins M, Kurpad AV, Pahwa D, Yadav AK, Sharma RR, Jha V, Marwaha N, Bhansali S, Bhansali A. Autologous bone marrow-derived mononuclear cells transplantation in type 2 diabetes mellitus: effect on beta-cell function and insulin sensitivity. Diabetol Metab Syndr. 2017 Jul 4;9:50. doi: 10.1186/s13098-017-0248-7. eCollection 2017. |
| D004700 | Endocrine System Diseases |
| D013812 | Therapeutics |
| D014180 | Transplantation |
| D013514 | Surgical Procedures, Operative |