Type 2 Diabetes Mellitus
Conditions
Brief summary
The purpose of this study is to improve the blood glucose level in type 2 diabetic patients.
Detailed description
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.
Interventions
BIOLOGICALmesenchymal stem cell transplantation
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 .
OTHERcontrol
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 .
BIOLOGICALMNC's TRANSPLANTATION
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 .
Sponsors
Post Graduate Institute of Medical Education and Research, Chandigarh
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
30 Years to 70 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | 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 |
Countries
India
Outcome results
None listed