Clinical trial NCT04134676: Therapeutic Potential of Stem Cell Conditioned Medium on Chronic Ulcer Wounds
Official title: Therapeutic Potential of Stem Cell Conditioned Medium on Chronic Ulcer Wounds : Pilot Study in Human
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Chronic Ulcer
Keywords: Stem Cell
Conditioned Medium
Lead sponsor: Sukma Skin Treatment
Sponsor class: OTHER
Collaborators: name: Stem Cell and Cancer Institute, Kalbe Farma Tbk
name: PT Pharma Metric Labs
First posted: 2019-10-22
Enrollment: 38
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Experimental clinical trial with open label
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Knowing the the success rate of chronic ulcer healing in patients undergoing wound care with conditioned medium
timeFrame: The ulcer is measured after 2 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Tangerang
country: Indonesia
facility: Mayapada Hospital
state: Banten
city: Tangerang
country: Indonesia
facility: Indra Clinic
state: Banten
city: Tangerang
country: Indonesia
facility: Sukma Cliniq
state: Banten
Study officials:
affiliation: Tarumanagara University
name: Sukmawati T Tan, Dr. dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: Tarumanagara University
name: Siufui Hendrawan, Dr. dr
role: STUDY_DIRECTOR
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