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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT04134676
Other study ID # PML-KLB-02-2019
Secondary ID
Status Completed
Phase Phase 1
First received
Last updated
Start date June 1, 2019
Est. completion date June 10, 2020

Study information

Verified date June 2020
Source Sukma Skin Treatment
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

Chronic wounds (CW) still represents a heavy burden to many patients and health care institution. Despite the most recent advances in wound management, up to 50% of chronic wounds still fail to heal. Conventional treatment of chronic wounds does not seem to work in several cases, consumes enormous amount of money and time, so it is necessary to develop different strategies. Previous studies have reported stem cells ability in tissue regenerations due mainly to its secreted paracrine factors, rather than its differentiation ability to become new cells. The factors is called secretomes, microvesicles, or exosomes, that can be found in the medium where the cells are growing, therefore it called conditioned medium (CM). Mesenchymal stem cells (MSCs) such as Wharton's Jelly Mesenchymal Stem Cells (WJ-MSC) appear to emerge as a promising wound healing therapy. To the best of investigator's knowledge, after conducted a pilot study using animal model to gain the preliminary data for the ulcer healing potential, this is the investigator's first clinical study to see the therapeutic potentials of Conditioned Medium Stem Cell as an additional growth factors in chronic skin ulcer healing and to compare the success of chronic ulcer healing in patients undergoing CM treatment and standard approach. The investigators will examine the therapeutic effect of human WJ-MSC-CM in wound healing on patients with chronic skin ulcer.


Description:

Treatment for chronic wound healing has become a great challenge in medical world. The incidence of chronic non healing wounds continues to increase and the classical method for wound healing therapy no longer reliable for chronic wounds healing. Therefore a new alternative strategy to control chronic wound healing is needed. Stem cell therapy has become a leading alternative strategy for wound healing therapy in this new modern world. The development of using conditioned medium such as Wharton's Jelly Mesenchymal Stem Cells have arising because of its paracrine factors that can provide a better healing process. During daily practice at the clinic, the authors sometimes find patients with chronic skin ulcers that cannot be treated using standard therapy. This encourages the authors to innovate new therapy to help the wound healing process by using human WJ-MSC conditioned medium.

This study has several purposes, such as; to observe the success rate, the differences in the period of time needed, and the differences in wound closure of chronic ulcer healing in patients undergoing wound care with conditioned medium and standard therapy. As for the benefits of research, these are the benefits; reducing the cost spent on treatment in chronic skin ulcer, faster chronic wound healing while minimizing the complications, improving the quality of therapy for patients with chronic skin ulcers, reducing the treatment period for chronic skin ulcer and can be used as the basis for future researchers to conduct further research on Conditioned Medium Stem Cell and chronic wound management.

Stem cell therapy constitutes a new alternative methods of wound healing. Many researchers are relying on this alternative new therapy that holds great potentials for its growth factors. Mesenchymal stem cell (MSCs) have been isolated from many types of adult tissues and fetal tissues, such as umbilical cord, skin, and placenta. When engrafted at sites of tissue injury, MSCs differentiate into connective tissue elements, support vasculogenesis, and secretes cytokines and growth factors that facilitate healing. As in wounds, MSCs differentiate into fibroblasts and pericytes and, perhaps, endothelial-like or vessel attached cells. WJ-MSCs secrete proangiogenic and wound healing promoting factors, such as transforming growth factor beta (TGF-β), vascular endothelial growth factor (VEGF), platelet-derived growth factor, insulin-like growth factor-I, interleukin (IL)-6 and IL-8.

The use of MSC-sourced secretome in regenerative medicine provides key advantages over stem-cell based applications such as; (a) resolving several safety considerations potentially associated with the transplantation of living and proliferative cell populations, (b) can be evaluated for safety, dosage and potency, (c) storage can be done without application of potentially toxic cryopreservative agents for a long period without loss of product potency, (d) using MSC-sourced secretome, such as conditioned medium (CM), is more economical and more practical for clinical application since it avoids invasive cell collection procedures, (e) the time and cost of expansion and maintenance of cultured stem cells could be greatly reduced, (f) finally, the biological product obtained for therapeutic applications could be modified to desired cell-specific effects.

This research is an experimental clinical trial with open label. This research will be conducted in Sitanala Village (RW 001), Mayapada Hospital, Indra Clinic and Sukma Clinic, Banten. Conditioned Medium Stem Cell obtained from SCI (PT. Kalbe Farma, Tbk.). The study started from June 2019 to June 2020. The sample used from this study are all outpatient and hospitalized patients with chronic skin ulcers at Mayapada Hospital, Indra Clinic, Sukma Clinic and Sitanala Village (RW 001) from June 2019 until May 2020. In this pilot study, 38 subjects will be included based on estimated sample size. The method of selecting samples is by using consecutive sampling. Data was collected by measuring the first ulcer and taking photos of each subject. The patient then use CM topical therapy and the evaluation is carried out after 2 weeks. Results are expressed as means ± SD. The normal distribution of the data was assessed using the Shapiro-Wilk test. For multiple comparisons One-Way Analysis of Variance (ANOVA) was used. The significance between two independent groups was determined by independent Student's t-test and the Mann-Whitney test. An unpaired t-test was performed if the data were normally distributed. Otherwise, a Mann-Whitney test was used. Statistical analysis was 2-tailed and values were considered statistically significant at p < 0.05.


Recruitment information / eligibility

Status Completed
Enrollment 38
Est. completion date June 10, 2020
Est. primary completion date May 10, 2020
Accepts healthy volunteers Accepts Healthy Volunteers
Gender All
Age group 18 Years to 80 Years
Eligibility Inclusion Criteria:

- Subjects with chronic skin ulcer that had received therapy for more than 1 month but there were no improvements

Exclusion Criteria:

- Respondent who refused to be the subject of this research

- ulcer size >10 x 15 cm

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Conditioned Media
Conditioned Media represents the complete regenerative milieu of cell-sourced secretome and vesicular elements. The soluble components of the secretome may be separated from the microvesicle fraction by centrifugation, filtration, polymer precipitation-based methodologies, ion exchange chromatography and size-exclusion chromatography. Both of these components may be capable of independently triggering regeneration and repair as well as of mediating the de novo organogenesis of tissue-engineered organs ex vivo.

Locations

Country Name City State
Indonesia Indra Clinic Tangerang Banten
Indonesia Mayapada Hospital Tangerang Banten
Indonesia Sukma Cliniq Tangerang Banten

Sponsors (3)

Lead Sponsor Collaborator
Sukma Skin Treatment PT. Pharma Metric Labs, Stem Cell and Cancer Institute, Kalbe Farma Tbk

Country where clinical trial is conducted

Indonesia, 

References & Publications (23)

Arno AI, Amini-Nik S, Blit PH, Al-Shehab M, Belo C, Herer E, Tien CH, Jeschke MG. Human Wharton's jelly mesenchymal stem cells promote skin wound healing through paracrine signaling. Stem Cell Res Ther. 2014 Feb 24;5(1):28. doi: 10.1186/scrt417. — View Citation

Beckermann BM, Kallifatidis G, Groth A, Frommhold D, Apel A, Mattern J, Salnikov AV, Moldenhauer G, Wagner W, Diehlmann A, Saffrich R, Schubert M, Ho AD, Giese N, Büchler MW, Friess H, Büchler P, Herr I. VEGF expression by mesenchymal stem cells contributes to angiogenesis in pancreatic carcinoma. Br J Cancer. 2008 Aug 19;99(4):622-31. doi: 10.1038/sj.bjc.6604508. Epub 2008 Jul 29. — View Citation

Bluestein D, Javaheri A. Pressure ulcers: prevention, evaluation, and management. Am Fam Physician. 2008 Nov 15;78(10):1186-94. — View Citation

Cerqueira MT, Pirraco RP, Marques AP. Stem Cells in Skin Wound Healing: Are We There Yet? Adv Wound Care (New Rochelle). 2016 Apr 1;5(4):164-175. Review. — View Citation

Choi M, Lee HS, Naidansaren P, Kim HK, O E, Cha JH, Ahn HY, Yang PI, Shin JC, Joe YA. Proangiogenic features of Wharton's jelly-derived mesenchymal stromal/stem cells and their ability to form functional vessels. Int J Biochem Cell Biol. 2013 Mar;45(3):560-70. doi: 10.1016/j.biocel.2012.12.001. Epub 2012 Dec 12. — View Citation

Coleman S, Gorecki C, Nelson EA, Closs SJ, Defloor T, Halfens R, Farrin A, Brown J, Schoonhoven L, Nixon J. Patient risk factors for pressure ulcer development: systematic review. Int J Nurs Stud. 2013 Jul;50(7):974-1003. doi: 10.1016/j.ijnurstu.2012.11.019. Epub 2013 Feb 1. Review. — View Citation

de la Garza-Rodea AS, Knaän-Shanzer S, van Bekkum DW. Pressure ulcers: description of a new model and use of mesenchymal stem cells for repair. Dermatology. 2011;223(3):266-84. doi: 10.1159/000334628. Epub 2011 Nov 23. — View Citation

Ho J, Walsh C, Yue D, Dardik A, Cheema U. Current Advancements and Strategies in Tissue Engineering for Wound Healing: A Comprehensive Review. Adv Wound Care (New Rochelle). 2017 Jun 1;6(6):191-209. doi: 10.1089/wound.2016.0723. Review. — View Citation

Khosrotehrani K. Mesenchymal stem cell therapy in skin: why and what for? Exp Dermatol. 2013 May;22(5):307-10. doi: 10.1111/exd.12141. — View Citation

Kim SM, Lim JY, Park SI, Jeong CH, Oh JH, Jeong M, Oh W, Park SH, Sung YC, Jeun SS. Gene therapy using TRAIL-secreting human umbilical cord blood-derived mesenchymal stem cells against intracranial glioma. Cancer Res. 2008 Dec 1;68(23):9614-23. doi: 10.1158/0008-5472.CAN-08-0451. — View Citation

Klopp AH, Gupta A, Spaeth E, Andreeff M, Marini F 3rd. Concise review: Dissecting a discrepancy in the literature: do mesenchymal stem cells support or suppress tumor growth? Stem Cells. 2011 Jan;29(1):11-9. doi: 10.1002/stem.559. Review. — View Citation

Li J, Chen J, Kirsner R. Pathophysiology of acute wound healing. Clin Dermatol. 2007 Jan-Feb;25(1):9-18. Review. — View Citation

McDaniel JC, Browning KK. Smoking, chronic wound healing, and implications for evidence-based practice. J Wound Ostomy Continence Nurs. 2014 Sep-Oct;41(5):415-23; quiz E1-2. doi: 10.1097/WON.0000000000000057. — View Citation

Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, Moorman MA, Simonetti DW, Craig S, Marshak DR. Multilineage potential of adult human mesenchymal stem cells. Science. 1999 Apr 2;284(5411):143-7. — View Citation

Posnett J, Franks PJ. The burden of chronic wounds in the UK. Nurs Times. 2008 Jan 22-28;104(3):44-5. Review. — View Citation

Sarasúa JG, López SP, Viejo MA, Basterrechea MP, Rodríguez AF, Gutiérrez AF, Gala JG, Menéndez YM, Augusto DE, Arias AP, Hernández JO. Treatment of pressure ulcers with autologous bone marrow nuclear cells in patients with spinal cord injury. J Spinal Cord Med. 2011;34(3):301-7. doi: 10.1179/2045772311Y.0000000010. — View Citation

Short B, Brouard N, Occhiodoro-Scott T, Ramakrishnan A, Simmons PJ. Mesenchymal stem cells. Arch Med Res. 2003 Nov-Dec;34(6):565-71. Review. — View Citation

Singh R, Singh R, Rohilla RK, Siwach R, Verma V, Kaur K. Surgery for pressure ulcers improves general health and quality of life in patients with spinal cord injury. J Spinal Cord Med. 2010;33(4):396-400. — View Citation

Sinno H, Prakash S. Complements and the wound healing cascade: an updated review. Plast Surg Int. 2013;2013:146764. doi: 10.1155/2013/146764. Epub 2013 Jul 24. — View Citation

Spaeth EL, Dembinski JL, Sasser AK, Watson K, Klopp A, Hall B, Andreeff M, Marini F. Mesenchymal stem cell transition to tumor-associated fibroblasts contributes to fibrovascular network expansion and tumor progression. PLoS One. 2009;4(4):e4992. doi: 10.1371/journal.pone.0004992. Epub 2009 Apr 7. Erratum in: PLoS One. 2013; 8(3). doi:10.1371/annotation/4ab4c130-16cb-41f0-9507-b00ce070fbc6. — View Citation

Turner NJ, Badylak SF. The Use of Biologic Scaffolds in the Treatment of Chronic Nonhealing Wounds. Adv Wound Care (New Rochelle). 2015 Aug 1;4(8):490-500. Review. — View Citation

Vizoso FJ, Eiro N, Cid S, Schneider J, Perez-Fernandez R. Mesenchymal Stem Cell Secretome: Toward Cell-Free Therapeutic Strategies in Regenerative Medicine. Int J Mol Sci. 2017 Aug 25;18(9). pii: E1852. doi: 10.3390/ijms18091852. Review. — View Citation

Xu Y, Guo S, Wei C, Li H, Chen L, Yin C, Zhang C. The Comparison of Adipose Stem Cell and Placental Stem Cell in Secretion Characteristics and in Facial Antiaging. Stem Cells Int. 2016;2016:7315830. doi: 10.1155/2016/7315830. Epub 2016 Feb 8. — View Citation

* Note: There are 23 references in allClick here to view all references

Outcome

Type Measure Description Time frame Safety issue
Primary Knowing the the success rate of chronic ulcer healing in patients undergoing wound care with conditioned medium Assessing ulcer progression macroscopic evaluation of:
The presence of granulation tissue
The size of the ulcer reduced
Edema decreases
Erythema decreases
Results are expressed as means ± SD. The normal distribution of the data was assessed using the Shapiro-Wilk test. For multiple comparisons One-Way Analysis of Variance (ANOVA) was used. The significance between two independent groups was determined by independent Student's t-test and the Mann-Whitney test. An unpaired t-test was performed if the data were normally distributed. Otherwise, a Mann-Whitney test was used. Statistical analysis was 2-tailed and values were considered statistically significant at p < 0.05.
The ulcer is measured after 2 weeks
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