BM-MNC and UCMSC for Type 2 Diabetes Mellitus Patients

T2D Clinical Trial

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"

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04501341
• Other study ID #: 132/PT02.FK25/U.Eu113/METEND/V
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: March 14, 2016
• Est. completion date: December 1, 2021

Study information

• Verified date: August 2020
• Source: Indonesia University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 15
• Est. completion date: December 1, 2021
• Est. primary completion date: December 1, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 30 Years to 65 Years

Eligibility

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)

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• T2D

Intervention

Biological:
• 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
• 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

Locations

Country	Name	City	State
Indonesia	Faculty of Medicine, Universitas Indonesia	Jakarta Pusat	DKI Jakarta

Sponsors (2)

Lead Sponsor	Collaborator
Indonesia University	Dr Cipto Mangunkusumo General Hospital

Country where clinical trial is conducted

Indonesia, 

References & Publications (12)

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. — View Citation

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

Féry F, Paquot N. [Etiopathogenesis and pathophysiology of type 2 diabetes]. Rev Med Liege. 2005 May-Jun;60(5-6):361-8. Review. French. — View 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:e2062. doi: 10.1038/cddis.2015.327. Review. — View 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. Epub 2015 Mar 9. — View 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. Epub 2012 Jul 13. — View 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. Review. — View 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. Review. — View 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. — View 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. Review. — View Citation

* Note: There are 12 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Before intervention, 1st, 3rd, 6th, and 12th month after intervention
Secondary	Increasing of C-peptide level	Measurements were obtained with mixed meal tolerance test	Before intervention, 1st, 3rd, 6th, and 12th month after intervention
Secondary	Decreasing of insulin resistance level	Measurement of HOMA-IR, calculated using fasting C-peptide and fasting plasma glucose formula	Before intervention, 1st, 3rd, 6th, and 12th month after intervention
Secondary	Immunology/inflammatory markers	Measurements of Interleukin-10 and TNF-alfa from serum and supernatant from PBMC stimulation	Before intervention, 1st, 3rd, 6th, and 12th month after intervention
Secondary	Adverse events	Thrombosis, hemorrhage, and infection	Up to 12 months after intervention
Secondary	HbA1c	Stable HbA1c or decreasing HbA1c (from baseline)	Before intervention, 1st, 3rd, 6th, and 12th month after intervention