Efficacy Of Autologous Bone Marrow Derived Stem Cell Transplantation In Patients With Type 2 Diabetes Mellitus-2

Study Overview
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Brief Summary
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The purpose of this study is to improve blood glucose control in Type 2 Diabetes mellitus patients.

Detailed Description
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We hypothesize that Autologous bone marrow derived stem cell transplantation(ABMSCT)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 ABMSCT 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 microenvironment which supports beta cell/resident stem cell activation and survival.

Official Title
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Efficacy 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: stem cell 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 OHA and on stable doses of insulin for atleast 3 months. On vildagliptin,pioglitazone and metformin for atleast 3 months along with Insulin to maintain euglycemia. HbA1c < 8.5%. Insulin requirement ≥0.4 IU/kg/d. GAD antibody negative status. Exclusion Criteria: Patients with T1DM 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/ cholelitiasis/ cholecystectomy Seropositivity for HIV, HBsAg and 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: 75 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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Group 1:Stem cell Recipient<br>Patients with Type 2 Diabetes mellitus on full doses of Vildagliptin+Pioglitazone+Metformin and requiring Insulin at dose of >0.4U/Kg for blood glucose control. They will undergo stem cell therapy initialy and G-CSF therapy at 2 months | Biological: stem cell transplantation<br>* Group 1: 200 - 250 ml of bone marrow will be aspirated and layered on density gradient medium (Ficoll - Hyperaque) and stem cells will be separated. Separated MNC's will be tagged with FDG-PET and injected into superior pancreatico duodenal artery and an PET scan will be done 2 hours later to see the percentage of stem cells homing in to pancreas. After 8 weeks G-CSF(10mcg/Kg/day) will be given subcutaneous for 5 days to achieve a Leucocyte count of >40,000/mm3. Patients will be urged to monitor and document blood glucose readings for next 6 months. Glucagon stimulated C - peptide, plasma Insulin, HOMA-IR , HOMA-B ,HbA1c, lipid profile and biochemistry will be done at baseline and 6 months .<br>* Other names: Autologous Bone marrow derived stem cell transplantation;|
| Group-2: Controls<br>Type 2 Diabetes mellitus patients on full doses of vildagliptin+metformin+pioglitazone and on Insulin >0.4U/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. | |

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 ABMSCT and Improvement in Glucagon stimulated C - peptide levels . |  | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Any reduction in requirement of insulin dosage and any improvement of HbA1c levels as compared to controls. |  | 6 months |