Tissue Distribution of F18-FDG Labelled Autologous Bone Marrow Derived Stem Cells in Patients With Type 2 DM

Study Overview
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Brief Summary
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Investigators purpose is to track stem cells in vivo in the type 2 diabetes mellitus patients after the same have been labelled with positron emission tomography tracer F18-FDG; as it is assumed that the therapeutic outcome will profoundly depend on the delivery of these cells to pancreas. Biodistribution and quantification studies will be done at 30 minutes and 90 minutes of stem cell infusion.

Detailed Description
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Autologous bone marrow derived stem cells have a promising potential in regenerative medicine. In particular the past decade has garnered a great interest in cellular therapy for treating Type2 diabetes mellitus. The pertinent questions in regenerative medicine today are to know about the homing, survival, differentiation and functionality of the cells and based on these to find out the adequate administration methods and choose the optimal dose and cell types. Various modalities have been used in the preclinical and clinical trials. These include MRI,optical imaging in the form of bioluminescence and fluorescence, quantum dots, SPECT and PET/CT imaging. However the methods which are suitable for stem cell tracking in small animals are not easily translated for human trials. In humans PET/CT imaging with its reasonable resolution and unique ability to combine anatomical and functional imaging is considered to be the best bet yet. Hence we intend to label the autologous bone marrow derived stem cells with PET tracer F18-FDG and carry out biodistribution studies, our ultimate aim being to study how in vivo distribution of the cells affect therapeutic efficacy.

Official Title
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Tissue Distribution of F18-FDG Labelled Autologous Bone Marrow Derived Stem Cells in Patients With Type 2 Diabetes Mellitus

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Other: Stem cell therapy- SPD artery
* Other: Stem cell therapy- splenic artery
* Other: Stem cell therapy-intravenous
* Other: Normal saline placebo -sham procedure


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with T2DM between 30 and 70 years of age. Failure to triple OHA 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 of 6.5-7.5% Insulin requirement ≥0.4 IU/kg/d. Glutamic acid decarboxylase (GAD 65) 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 pancreatitis 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. Female patients who are pregnant or lactating

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: Stem cell therapy - SPD artery<br>Stem cells will be infused into the superior pancreaticoduodenal artery. | Other: Stem cell therapy- SPD artery<br>* A total of 28 patients will be enrolled and randomized to four groups of 7 patients each. 7 patients will receive stem cell infusion into the superior pancreaticoduodenal artery. Another 7 patients will be given stem cell infusion into the splenic artery. The next batch of 7 patients will receive stem cell infusion from the peripheral intravenous route and 7 patients will act as controls undergoing a sham procedure with infusion of normal saline.<br>* Other names: Bone marrow mononuclear cells;|
| Active Comparator: Stem cell therapy - splenic artery<br>Stem cells will be infused into the splenic artery. | Other: Stem cell therapy- splenic artery<br>* 7 patients will receive stem cells infusion through splenic artery.<br>|
| Active Comparator: Stem cell therapy-intravenous<br>Stem cells will be given intravenously. | Other: Stem cell therapy-intravenous<br>* 7 patients will receive stem cells infusion through peripheral intravenous route.<br>|
| Placebo Comparator: Normal saline placebo -sham procedure<br>Sham procedure with infusion of normal saline. | Other: Normal saline placebo -sham procedure<br>* 7 patients will receive infusion of normal saline and will act as control groups<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| • Increment in glucagon stimulated C - peptide levels at the end of 6 months of ABMSCT, as compared to baseline |  | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| • Any reduction in requirement of insulin dosage measured as a percentage decrease from baseline • Improvement of HbA1c levels as compared to baseline |  | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Type 2 diabetes mellitus, F18-FDG labelled stem cells