Efficacy Of Autologous Bone Marrow Derived Stem Cell Transplantation In Patients With Type 2 Diabetes Mellitus
Condition: Type 2 Diabetes Mellitus
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2
Study type: Interventional
Phase: Phase 2

Summary: 
      India is the "Diabetes Capital of the World" with 41 million Indians having diabetes i.e.
      every fifth diabetic in the world is an Indian1. Type 2 Diabetes Mellitus (T2DM) constitutes
      the major chunk of diabetes and has insulin resistance as the hallmark feature in the
      pathogenesis. However, with the progression of the disease the insulin resistance becomes
      stable whereas β - cell function shows a gradual decline due to its ongoing apoptosis2. This
      ultimately leads to inability of the β - cells to cope up with the increased demand of
      insulin caused due to insulin resistance and manifests as hyperglycemia. As β - cell failure
      is progressive and inexorable, as demonstrated in United Kingdom Prospective Diabetes Study3,
      most of the patients with T2DM would eventually require insulin and it would be difficult to
      achieve to attain a strict glycemic control . It is well known that diabetes related
      complications which account for morbidity and mortality in this disease can be prevented or
      delayed by strict glycemic control. However, even with intensive insulin therapy it has been
      shown that glycemic control can never be perfect with patients exhibiting hyperglycemia or
      hypoglycemia during 24 hour glucose profile4. Also insulin therapy is not physiological as
      there is no hepatic "first - pass" metabolism of insulin which is required for halting the
      hepatic glucose output, which is responsible for fasting hyperglycemia5. This led the
      researchers to evolve various strategies of β - cell replacement therapy e.g. pancreatic
      transplantation and islet cell transplantation. Initially the results of islet cell
      transplantation were dismal but after the induction of glucocorticoid free immunosuppressive
      therapy and the use of adequate number of islet cells from multiple donors, the results of
      islet cell transplantation have been better6. However, islet cell transplantation has its own
      limitations viz insufficient supply, being technically demanding and requirement of lifelong
      immunosuppressive therapy in the recipient.

      These shortcomings can be overcome by the use of stem cells which is an inexhaustible source
      of β -cells. Stem cells are primitive cells capable of differentiating into mature cells of
      the body of various lineages. Stem cells can be obtained from various sources like blastocyst
      (embryonal stem cells), umbilical cord or bone marrow. There is an evidence to suggest that
      stem cell transplantation can lead to improvement in pancreatic endocrine function and
      improvement in glycemic control in diabetic mice7,8,9,10 through various mechanisms such as
      transdifferentiation or regeneration of endothelial cell in the damaged islets which in turn
      lead to regeneration of islet cells by paracrine action11. However, till date there is no
      study that demonstrates that stem cell therapy can be effective in patients with T2DM for
      their glycemic control.

      The investigators propose to carry out autologous bone marrow - derived stem cell
      transplantation (ABMSCT) in patients of T2DM, obtained from their own bone marrow and its
      superselective injection into the gastroduodenal artery after purification without any
      immunosuppressive regimen.

      Aim:

      The aim of this study is to reverse hyperglycemia and insulin dependency by ABMSCT in
      patients with type 2 diabetes mellitus.

      Hypothesis:

      The investigators hypothesize that ABMSCT into the pancreas of patients with T2DM, aged more
      than 30 years with insulin requirement of 0.7 U/ kg body weight/day or 50 U / day whichever
      is lesser, 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 will lead these
      patients to regenerate functional β - cells by transdifferentiation or by regeneration of
      endothelial cell which in turn cause β - cells neogenesis by paracrine effect.

      Objectives:

      Primary objective:

        1. Abolition or reduction of insulin requirement by > 50% by the end of 6 months of ABMSCT.

        2. To evaluate the increment of Glucagon stimulated C - peptide response at the end of 6
           months of ABMSCT, as compared to the baseline values.

      Secondary objective:

        1. Any reduction in requirement of insulin dosage.

        2. Improvement of HbA1c levels as compared to baseline.
    


Intervention name(s): stem cell harvest; angiographic transplantation of stem cells
Intervention type(s): Biological; Procedure
Intervention description(s): stem cells will be harvested from the iliac crest of the patients; autologous bone marrow derived stem cells will be transplanted in the gastroduodenal artery of the patient angiographically
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: stem cell therapy; T2DM; Efficacy Of Autologous Bone Marrow Derived Stem Cell Transplantation In Patients With Type 2 Diabetes Mellitus