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

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ClinicalTrials.gov Identifier: NCT00644241
Recruitment Status : Completed
First Posted : March 26, 2008
Last Update Posted : October 21, 2015
Sponsor:
Information provided by (Responsible Party):
Anil Bhansali, Postgraduate Institute of Medical Education and Research

Tracking Information
First Submitted Date  ICMJE March 20, 2008
First Posted Date  ICMJE March 26, 2008
Last Update Posted Date October 21, 2015
Study Start Date  ICMJE January 2008
Actual Primary Completion Date June 2009   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 25, 2008)
  • Abolition or reduction of insulin requirement by > 50% by the end of 6 months of ABMSCT [ Time Frame: 6 months ]
  • Increment in glucagon stimulated C - peptide levels at the end of 6 months of ABMSCT, as compared to baseline [ Time Frame: 6 months ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 25, 2008)
  • Any reduction in requirement of insulin dosage [ Time Frame: 6 months ]
  • Improvement of HbA1c levels as compared to baseline [ Time Frame: 6 months ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Efficacy Of Autologous Bone Marrow Derived Stem Cell Transplantation In Patients With Type 2 Diabetes Mellitus
Official Title  ICMJE Efficacy Of Autologous Bone Marrow Derived Stem Cell Transplantation In Patients With Type 2 Diabetes Mellitus
Brief 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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Type 2 Diabetes Mellitus
Intervention  ICMJE
  • Biological: stem cell harvest
    stem cells will be harvested from the iliac crest of the patients
  • Procedure: angiographic transplantation of stem cells
    autologous bone marrow derived stem cells will be transplanted in the gastroduodenal artery of the patient angiographically
Study Arms  ICMJE Experimental: stem cell
Interventions:
  • Biological: stem cell harvest
  • Procedure: angiographic transplantation of stem cells
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: March 25, 2008)
10
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE June 2009
Actual Primary Completion Date June 2009   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Patients with type 2 diabetes mellitus more than 30 and less than 75 years of age.
  2. Insulin requirement 0.7 IU/kg/d or 50 IU/d, whichever is lesser.
  3. GAD antibody negative status.

Exclusion Criteria:

  1. Patients with T1DM or secondary diabetes.
  2. Patients with serum creatinine > 1.5 mg/dl.
  3. 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).
  4. History of myocardial infarction or unstable angina in the previous 3 months.
  5. History of malignancy or current malignancy other than non-melanomatous skin cancer.
  6. Patients with active infections
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 30 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE India
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00644241
Other Study ID Numbers  ICMJE SCT
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Anil Bhansali, Postgraduate Institute of Medical Education and Research
Study Sponsor  ICMJE Postgraduate Institute of Medical Education and Research
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Postgraduate Institute of Medical Education and Research
Verification Date October 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP