Bone Marrow Derived Stem Cell Transplantation in T2DM

Study Overview
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Brief Summary
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The purpose of this study is to improve the blood glucose level in type 2 diabetic patients.

Detailed Description
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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.

Official Title
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Efficacy and Safety of Autologous Bone Marrow Derived Stem Cell Transplantation in Patients With Type 2 Diabetes Mellitus

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Biological: mesenchymal stem cell transplantation
* Other: control
* Biological: MNC's TRANSPLANTATION


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with type 2 diabetes mellitus between 30 and 70 years of age. Failure to triple oral hypoglycemic agent and on stable doses of insulin for at least 3 months. On vildagliptin,pioglitazone and metformin for at least 3 months along with Insulin to maintain euglycemia. HbA1c < 7.5%. Insulin requirement ≥0.4 IU/kg/d. GAD antibody negative status. Exclusion Criteria: Patients with type 1 diabetes mellitus or secondary diabetes. Patients with serum creatinine > 1.5 mg/dl. Abnormal liver function tests (defined as value of transaminases > 3 times the upper value of normal or serum bilirubin higher than normal for the reference value for the laboratory). History of cholecystitis/ cholelithiasis/ cholecystectomy Seropositivity for HIV, HBsAg and hepatitis C virus (HCV). History of myocardial infarction or unstable angina in the previous 3 months. History of malignancy Patients with active infections.

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 70 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: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: mesenchymal stem cell transplantation<br>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. | Biological: mesenchymal stem cell transplantation<br>* 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 .<br>|
| Sham Comparator: Control<br>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 | Other: control<br>* 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 .<br>|
| Experimental: MNC's TRANSPLANTATION<br>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. | Biological: MNC's TRANSPLANTATION<br>* 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 .<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | 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 |