Back to resultsBM-MNC and UCMSC for Type 2 Diabetes Mellitus Patients
Primary Purpose
T2D
Status
Unknown status
Phase
Phase 1
Locations
Indonesia
Study Type
Interventional
Intervention
Bone-marrow aspiration, Intra-pancreatic Catheterisation of BM-MNC
Intravenous Infusion of UC-MSC
Sponsored by
About this trial
This is an interventional treatment trial for T2D focused on measuring type 2 diabetes, Bone-marrow mononuclear cells, Umbilical cord mesenchymal stem cells, Glycemic control
Eligibility Criteria
Inclusion Criteria:
- Type 2 diabetes patients on insulin therapy with or without oral hypoglycemic agents, with total daily dose of insulin >= 0,5 unit/kg body weight
- Stable HbA1C in the last six months (HbA1c <= 8.5%)
Exclusion Criteria:
- Type 1 diabetes mellitus
- eGFR < 45 mL/min/m2 (for BM-MNC)
- Liver disease (moderate- severe)
- Active infection
- Contrast hypersensitivity (for BM-MNC)
- History of Malignancy
- Acute coronary syndrome in last three months
- Coronary arterial diseases with significant stenosis and has not carried out revascularization
- Pregnancy (for women subjects)
Sites / Locations
- Faculty of Medicine, Universitas IndonesiaRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
BM-MNC experimental
UC-MSC
Arm Description
Autologue bone marrow mononuclear cell
Umbilical cord mesenchymal stem cell
Outcomes
Primary Outcome Measures
Decreasing total daily dose of insulin (>= 30%)
After intervention, blood glucose level will be reported by the subjects on weekly basis. The insulin dose and/or oral medication will be adjusted accordingly.
Secondary Outcome Measures
Increasing of C-peptide level
Measurements were obtained with mixed meal tolerance test
Decreasing of insulin resistance level
Measurement of HOMA-IR, calculated using fasting C-peptide and fasting plasma glucose formula
Immunology/inflammatory markers
Measurements of Interleukin-10 and TNF-alfa from serum and supernatant from PBMC stimulation
Adverse events
Thrombosis, hemorrhage, and infection
HbA1c
Stable HbA1c or decreasing HbA1c (from baseline)
Full Information
NCT ID
NCT04501341
First Posted
July 26, 2020
Last Updated
August 2, 2020
Sponsor
Indonesia University
Collaborators
Dr Cipto Mangunkusumo General Hospital
1. Study Identification
Unique Protocol Identification Number
NCT04501341
Brief Title
BM-MNC and UCMSC for Type 2 Diabetes Mellitus Patients
Official Title
Effectivity and Safety of Autologous BM-MNC Stem Cell Therapy and Allogenic Umbilical Cord Mesenchymal Stem Cell for Type 2 Diabetes Mellitus Patients"
Study Type
Interventional
2. Study Status
Record Verification Date
August 2020
Overall Recruitment Status
Unknown status
Study Start Date
March 14, 2016 (Actual)
Primary Completion Date
December 1, 2021 (Anticipated)
Study Completion Date
December 1, 2021 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Indonesia University
Collaborators
Dr Cipto Mangunkusumo General Hospital
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The aim of this preliminary study is to evaluate the safety and efficacy of bone-marrow mononuclear cells (BM-MNCs) and umbilical-cord tissue-derived mesenchymal stem cells (UC-MSCs) administration in type 2 diabetes patients
Detailed Description
Type 2 diabetes (T2D) patients had peripheral insulin resistance accompanied by progressive pancreatic beta cell degeneration and dysfunction due to glucotoxicity and lipotoxicity. Several studies have shown that the immune system plays a significant role in the pathogenesis of T2D. Bone-marrow mononuclear cells (BM-MNCs) and umbilical-cord tissue-derived mesenchymal stem cells (UC-MSCs) via its immunomodulatory properties have the potential to improve insulin resistance condition and pancreatic beta-cells dysfunction thus improve the glycemic control and insulin requirement in T2D patients. In this pilot study, we plan to recruit 15 T2D patients with total daily dose of insulin >= 0.5 unit/kgBW/day to receive BM-MNCs (5 subjects) or UC-MSCs injections (10 subjects). These subjects will be closely followed up for 12 months for evaluation of primary and secondary outcome.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
T2D
Keywords
type 2 diabetes, Bone-marrow mononuclear cells, Umbilical cord mesenchymal stem cells, Glycemic control
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Model Description
5 subjects receive BM-MNC and 10 subjects receive UC-MSC
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
15 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
BM-MNC experimental
Arm Type
Experimental
Arm Description
Autologue bone marrow mononuclear cell
Arm Title
UC-MSC
Arm Type
Experimental
Arm Description
Umbilical cord mesenchymal stem cell
Intervention Type
Biological
Intervention Name(s)
Bone-marrow aspiration, Intra-pancreatic Catheterisation of BM-MNC
Intervention Description
Autologous bone-marrow mononuclear cells infused to the main blood vessels that supply the pancreas according to the results of previous pancreatic CT-scan, performed by interventional radiologist. The target is to distribute the BM-MNCs equally in all part of the pancreas. Dosage: 1 x 10^5 - 1 x 10^6 CD34 cells/kgBW
Intervention Type
Biological
Intervention Name(s)
Intravenous Infusion of UC-MSC
Intervention Description
Allogeneic umbilical cord tissue-derived mesenchymal stem cells will be given via intravenous infusion. Dosage: 2 x 10^6 cells/kgBW, twice, with three months interval
Primary Outcome Measure Information:
Title
Decreasing total daily dose of insulin (>= 30%)
Description
After intervention, blood glucose level will be reported by the subjects on weekly basis. The insulin dose and/or oral medication will be adjusted accordingly.
Time Frame
Before intervention, 1st, 3rd, 6th, and 12th month after intervention
Secondary Outcome Measure Information:
Title
Increasing of C-peptide level
Description
Measurements were obtained with mixed meal tolerance test
Time Frame
Before intervention, 1st, 3rd, 6th, and 12th month after intervention
Title
Decreasing of insulin resistance level
Description
Measurement of HOMA-IR, calculated using fasting C-peptide and fasting plasma glucose formula
Time Frame
Before intervention, 1st, 3rd, 6th, and 12th month after intervention
Title
Immunology/inflammatory markers
Description
Measurements of Interleukin-10 and TNF-alfa from serum and supernatant from PBMC stimulation
Time Frame
Before intervention, 1st, 3rd, 6th, and 12th month after intervention
Title
Adverse events
Description
Thrombosis, hemorrhage, and infection
Time Frame
Up to 12 months after intervention
Title
HbA1c
Description
Stable HbA1c or decreasing HbA1c (from baseline)
Time Frame
Before intervention, 1st, 3rd, 6th, and 12th month after intervention
10. Eligibility
Sex
All
Minimum Age & Unit of Time
30 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Type 2 diabetes patients on insulin therapy with or without oral hypoglycemic agents, with total daily dose of insulin >= 0,5 unit/kg body weight
Stable HbA1C in the last six months (HbA1c <= 8.5%)
Exclusion Criteria:
Type 1 diabetes mellitus
eGFR < 45 mL/min/m2 (for BM-MNC)
Liver disease (moderate- severe)
Active infection
Contrast hypersensitivity (for BM-MNC)
History of Malignancy
Acute coronary syndrome in last three months
Coronary arterial diseases with significant stenosis and has not carried out revascularization
Pregnancy (for women subjects)
Facility Information:
Facility Name
Faculty of Medicine, Universitas Indonesia
City
Jakarta Pusat
State/Province
DKI Jakarta
ZIP/Postal Code
10430
Country
Indonesia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Pradana Soewondo, Prof
Phone
+628188160756
Email
pradana.soewondo@ui.ac.id
12. IPD Sharing Statement
Citations:
PubMed Identifier
24457898
Citation
Itariu BK, Stulnig TM. Autoimmune aspects of type 2 diabetes mellitus - a mini-review. Gerontology. 2014;60(3):189-96. doi: 10.1159/000356747. Epub 2014 Jan 22.
Results Reference
background
PubMed Identifier
25999531
Citation
Tsai S, Clemente-Casares X, Revelo XS, Winer S, Winer DA. Are obesity-related insulin resistance and type 2 diabetes autoimmune diseases? Diabetes. 2015 Jun;64(6):1886-97. doi: 10.2337/db14-1488.
Results Reference
background
PubMed Identifier
19817513
Citation
Campbell RK, Martin TM. The chronic burden of diabetes. Am J Manag Care. 2009 Sep;15(9 Suppl):S248-54.
Results Reference
background
PubMed Identifier
16035295
Citation
Fery F, Paquot N. [Etiopathogenesis and pathophysiology of type 2 diabetes]. Rev Med Liege. 2005 May-Jun;60(5-6):361-8. French.
Results Reference
background
PubMed Identifier
28066789
Citation
Wehbe T, Chahine NA, Sissi S, Abou-Joaude I, Chalhoub L. Bone marrow derived stem cell therapy for type 2 diabetes mellitus. Stem Cell Investig. 2016 Dec 6;3:87. doi: 10.21037/sci.2016.11.14. eCollection 2016.
Results Reference
background
PubMed Identifier
26136869
Citation
Guan LX, Guan H, Li HB, Ren CA, Liu L, Chu JJ, Dai LJ. Therapeutic efficacy of umbilical cord-derived mesenchymal stem cells in patients with type 2 diabetes. Exp Ther Med. 2015 May;9(5):1623-1630. doi: 10.3892/etm.2015.2339. Epub 2015 Mar 9.
Results Reference
background
PubMed Identifier
19364067
Citation
Estrada EJ, Valacchi F, Nicora E, Brieva S, Esteve C, Echevarria L, Froud T, Bernetti K, Cayetano SM, Velazquez O, Alejandro R, Ricordi C. Combined treatment of intrapancreatic autologous bone marrow stem cells and hyperbaric oxygen in type 2 diabetes mellitus. Cell Transplant. 2008;17(12):1295-304. doi: 10.3727/096368908787648119.
Results Reference
background
PubMed Identifier
23561959
Citation
Bhansali A, Asokumar P, Walia R, Bhansali S, Gupta V, Jain A, Sachdeva N, Sharma RR, Marwaha N, Khandelwal N. Efficacy and safety of autologous bone marrow-derived stem cell transplantation in patients with type 2 diabetes mellitus: a randomized placebo-controlled study. Cell Transplant. 2014;23(9):1075-85. doi: 10.3727/096368913X665576.
Results Reference
background
PubMed Identifier
22814142
Citation
Hu J, Li C, Wang L, Zhang X, Zhang M, Gao H, Yu X, Wang F, Zhao W, Yan S, Wang Y. Long term effects of the implantation of autologous bone marrow mononuclear cells for type 2 diabetes mellitus. Endocr J. 2012;59(11):1031-9. doi: 10.1507/endocrj.ej12-0092. Epub 2012 Jul 13.
Results Reference
background
PubMed Identifier
23093863
Citation
Chao YH, Wu HP, Chan CK, Tsai C, Peng CT, Wu KH. Umbilical cord-derived mesenchymal stem cells for hematopoietic stem cell transplantation. J Biomed Biotechnol. 2012;2012:759503. doi: 10.1155/2012/759503. Epub 2012 Oct 3.
Results Reference
background
PubMed Identifier
31214172
Citation
Weiss ARR, Dahlke MH. Immunomodulation by Mesenchymal Stem Cells (MSCs): Mechanisms of Action of Living, Apoptotic, and Dead MSCs. Front Immunol. 2019 Jun 4;10:1191. doi: 10.3389/fimmu.2019.01191. eCollection 2019.
Results Reference
result
PubMed Identifier
26794657
Citation
Gao F, Chiu SM, Motan DA, Zhang Z, Chen L, Ji HL, Tse HF, Fu QL, Lian Q. Mesenchymal stem cells and immunomodulation: current status and future prospects. Cell Death Dis. 2016 Jan 21;7(1):e2062. doi: 10.1038/cddis.2015.327.
Results Reference
result
Learn more about this trial
BM-MNC and UCMSC for Type 2 Diabetes Mellitus Patients
We'll reach out to this number within 24 hrs