Bone Marrow Derived Stem Cell Transplantation in T2DM

NCT ID: NCT01759823

Last Updated: 2015-10-27

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2/PHASE3

Total Enrollment

30 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-12-31

Study Completion Date

2015-10-31

Brief Summary

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The purpose of this study is to improve the blood glucose level in type 2 diabetic patients.

Detailed Description

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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.

Conditions

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Type 2 Diabetes Mellitus

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Participants

Study Groups

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mesenchymal stem cell transplantation

Patients with Type 2 Diabetes mellitus on full doses of Vildagliptin+Pioglitazone+Metformin and requiring Insulin at dose of \>0.4unit/Kg for blood glucose control.

Group Type EXPERIMENTAL

mesenchymal stem cell transplantation

Intervention Type BIOLOGICAL

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 .

Control

vildagliptin+metformin+pioglitazone and on Insulin \>0.4unit/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

Group Type SHAM_COMPARATOR

control

Intervention Type OTHER

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 .

MNC's TRANSPLANTATION

Patients with Type 2 Diabetes mellitus on full doses of Vildagliptin+Pioglitazone+Metformin and requiring Insulin at dose of \>0.4unit/Kg for blood glucose control.

Group Type EXPERIMENTAL

MNC's TRANSPLANTATION

Intervention Type BIOLOGICAL

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 .

Interventions

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mesenchymal 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 .

Intervention Type BIOLOGICAL

control

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 .

Intervention Type OTHER

MNC'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 .

Intervention Type BIOLOGICAL

Eligibility Criteria

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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.
Minimum Eligible Age

30 Years

Maximum Eligible Age

70 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Post Graduate Institute of Medical Education and Research, Chandigarh

OTHER

Sponsor Role lead

Responsible Party

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Anil Bhansali

Professor and HOD

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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A Bhansali

Role: STUDY_CHAIR

Post Graduate Institute of Medical Education and Research, Chandigarh

V Jha

Role: PRINCIPAL_INVESTIGATOR

Post Graduate Institute of Medical Education and Research, Chandigarh

Neelam Marwaha

Role: PRINCIPAL_INVESTIGATOR

Post Graduate Institute of Medical Education and Research, Chandigarh

Locations

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Postgraduate Institute of Medical Education and Research

Chandigarh, Uttarakhand, India

Site Status

Countries

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India

References

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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.

Reference Type BACKGROUND
PMID: 19686048 (View on PubMed)

Bhansali S, Dutta P, Yadav MK, Jain A, Mudaliar S, Hawkins M, Kurpad AV, Pahwa D, Yadav AK, Sharma RR, Jha V, Marwaha N, Bhansali S, Bhansali A. Autologous bone marrow-derived mononuclear cells transplantation in type 2 diabetes mellitus: effect on beta-cell function and insulin sensitivity. Diabetol Metab Syndr. 2017 Jul 4;9:50. doi: 10.1186/s13098-017-0248-7. eCollection 2017.

Reference Type DERIVED
PMID: 28690682 (View on PubMed)

Other Identifiers

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stem cell therapy in T2DM

Identifier Type: -

Identifier Source: org_study_id

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