BM-MNC and UCMSC for Type 2 Diabetes Mellitus Patients

NCT ID: NCT04501341

Last Updated: 2020-08-06

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

UNKNOWN

Clinical Phase

PHASE1/PHASE2

Total Enrollment

15 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-03-14

Study Completion Date

2021-12-01

Brief Summary

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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

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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.

Conditions

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T2D

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

5 subjects receive BM-MNC and 10 subjects receive UC-MSC
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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BM-MNC experimental

Autologue bone marrow mononuclear cell

Group Type EXPERIMENTAL

Bone-marrow aspiration, Intra-pancreatic Catheterisation of BM-MNC

Intervention Type BIOLOGICAL

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

UC-MSC

Umbilical cord mesenchymal stem cell

Group Type EXPERIMENTAL

Intravenous Infusion of UC-MSC

Intervention Type BIOLOGICAL

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

Interventions

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Bone-marrow aspiration, Intra-pancreatic Catheterisation of BM-MNC

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

Intravenous Infusion of UC-MSC

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

Intervention Type BIOLOGICAL

Eligibility Criteria

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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)
Minimum Eligible Age

30 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Dr Cipto Mangunkusumo General Hospital

OTHER

Sponsor Role collaborator

Indonesia University

OTHER

Sponsor Role lead

Responsible Party

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Prof. Dr. dr. Pradana Soewondo, SpPD-KEMD

Prof

Responsibility Role PRINCIPAL_INVESTIGATOR

Locations

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Faculty of Medicine, Universitas Indonesia

Jakarta Pusat, DKI Jakarta, Indonesia

Site Status RECRUITING

Countries

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Indonesia

Facility Contacts

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Pradana Soewondo, Prof

Role: primary

+628188160756

References

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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.

Reference Type BACKGROUND
PMID: 24457898 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25999531 (View on PubMed)

Campbell RK, Martin TM. The chronic burden of diabetes. Am J Manag Care. 2009 Sep;15(9 Suppl):S248-54.

Reference Type BACKGROUND
PMID: 19817513 (View on PubMed)

Fery F, Paquot N. [Etiopathogenesis and pathophysiology of type 2 diabetes]. Rev Med Liege. 2005 May-Jun;60(5-6):361-8. French.

Reference Type BACKGROUND
PMID: 16035295 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 28066789 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 26136869 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 19364067 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 23561959 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22814142 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 23093863 (View on PubMed)

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.

Reference Type RESULT
PMID: 31214172 (View on PubMed)

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.

Reference Type RESULT
PMID: 26794657 (View on PubMed)

Other Identifiers

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132/PT02.FK25/U.Eu113/METEND/V

Identifier Type: -

Identifier Source: org_study_id

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