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

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

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

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes Mellitus
• Intervention / Treatment: Biological: stem cell transplantation

Detailed Description

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.

• Study Type: Observational
• Enrollment (Actual): 30

Contacts and Locations

Study Locations

• India
  • Chandigarh UT
    • Chandigarh, Chandigarh UT, India
      • Post Graduate Institute of Medical Education and Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Patients with type 2 Diabetes mellitus with triple Oral hypoglycemic failure and on Insulin for glycemic control

Description

Inclusion Criteria:

1. Patients with type 2 diabetes mellitus between 30 and 70 years of age.
2. Failure to triple OHA and on stable doses of insulin for atleast 3 months.
3. On vildagliptin,pioglitazone and metformin for atleast 3 months along with Insulin to maintain euglycemia.
4. HbA1c < 8.5%.
5. Insulin requirement ≥0.4 IU/kg/d.
6. 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 cholecystitis/ cholelitiasis/ cholecystectomy
5. Seropositivity for HIV, HBsAg and HCV.
6. History of myocardial infarction or unstable angina in the previous 3 months.
7. History of malignancy
8. Patients with active infections.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Group 1:Stem cell Recipient; 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; 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 .; Other Names: Autologous Bone marrow derived stem cell transplantation
Group-2: Controls; 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?

Primary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Postgraduate Institute of Medical Education and Research
• Investigators: Study Chair: Anil Bhansali, MD.,DM, Postgraduate Institute of Medical Education and Research; Principal Investigator: Neelam Marwaha, MD.,DM, Postgraduate Institute of Medical Education and Research; Principal Investigator: N Khandelwal, MD, Postgraduate Institute of Medical Education and Research; Principal Investigator: B.R. Mittal, MD, Postgraduate Institute of Medical Education and Research; Principal Investigator: Prem Kumar, MD, Postgraduate Institute of Medical Education and Research; Principal Investigator: Rama Walia, MD.,DM, Postgraduate Institute of Medical Education and Research

Publications and helpful links

General Publications

• Bhansali A, Upreti V, Khandelwal N, Marwaha N, Gupta V, Sachdeva N, Sharma RR, Saluja K, Dutta P, Walia R, Minz R, Bhadada S, Das S, Ramakrishnan S. Efficacy of autologous bone marrow-derived stem cell transplantation in patients with type 2 diabetes mellitus. Stem Cells Dev. 2009 Dec;18(10):1407-16. doi: 10.1089/scd.2009.0164.

Study record dates

Study Major Dates

• Study Start: November 1, 2009
• Primary Completion (Actual): July 1, 2011
• Study Completion (Actual): July 1, 2011

Study Registration Dates

• First Submitted: February 8, 2010
• First Submitted That Met QC Criteria: February 8, 2010
• First Posted (Estimate): February 9, 2010

Study Record Updates

• Last Update Posted (Estimate): October 21, 2015
• Last Update Submitted That Met QC Criteria: October 19, 2015
• Last Verified: October 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2
• Other Study ID Numbers: ABMSCT2