Allogeneic ADSCs and Platelet-Poor Plasma Fibrin Hydrogel to Treat the Patients With Burn Wounds (ADSCs-BWs) (ADSCs-BWs)

Safety and Efficacy Evaluation of Tissue Engineered Construct Based on Allogeneic Adipose-derived Multipotent Mesenchymal Stromal Cells and Platelet-poor Plasma Fibrin Hydrogel to Treat the Patients With Burn Wounds

The purpose of this study is to evaluate safety and efficacy of tissue engineered construct based on allogeneic cultured adipose-derived multipotent mesenchymal stromal cells (ALLO-ADSCs) and platelet-poor plasma fibrin hydrogel to treat patients with 2-B and 3- degree burn wounds

Study Overview

• Status: Unknown
• Conditions: Second- or Third-degree Burns
• Intervention / Treatment: Biological: ALLO-ASCs

Detailed Description

For more than 20 years in clinical practice allogeneic transplantation of diploid fibroblasts (ADP) for burn wounds has been successfully used, it is used as an independent method, and a method of preparing wounds for autologous skin grafting [1].

The clinical efficacy of transplantation ADP, after the research done by E.V. Glushchenko; Rahayev AM [2,3] is not doubted.

Several studies have shown the efficacy of stem cells in promoting faster and superior wound healing. Alexaki [4] successfully used adipose derived mesenchymal stem cells in wound healing in mice and compared their effect with dermal fibroblasts. The application of stem cells in wounds promoted more efficient reepithelialization by their proliferative effect on keratinocytes.

In recent years, the world's leading burn centers attempted to restore the skin over large areas of burn wounds by epidermal layers transplantation of allogeneic cells cultured in culture medium.

The information expected in the study will be based on the principles of evidence-based medicine and will have practical significance for the treatment of burn wounds.

It is expected to show a positive effect of cultured multipotent mesenchymal stromal cells in the epithelization of burn wounds process as well as the extent and speed healing of skin flap during autologous skin grafting.

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Ukraine
  • Kyiv, Ukraine, 02094,13, Krakivska, str.,
    • Recruiting
    • The Kyiv City Clinical Hospital №2
    • Contact: Georgiy P. Kozynets, MD, PhD, DSc; Phone Number: +380973917611; Email: dr.g.kozynets@gmail.com
    • Contact: Nataliia M. Olijnyk, PhD; Phone Number: +380904040116; Email: N.Olijnyk@ilaya.ua
    • Sub-Investigator: Dmytro O. Zubov, PhD
    • Sub-Investigator: Roman G. Vasyliev

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male and female aged 18-65 years;
• Patients with 2-nd B and 3-d degree burn wound;
• Body surface area involved in burns - from 10 to 50%;
• The area of skin grafting - less than 6% of the skin surface;
• Burn occurring within the 24 hours prior to the hospitalization;
• Adequate antishock therapy in the prehospital phase;
• Women of childbearing age to provide proof of a current, valid negative pregnancy test;
• Confirmation of participation in the study by signing the Instrument of Consent, personally or through a responsible caretaker.

Exclusion Criteria:

• Prognostically favorable or unfavorable outcome of the disease
• (Lesion Severity Index, less than 30 or more, than 120 score);
• Combined trauma;
• Severe respiratory tract burn injuries;
• Ischemic disease of the lower extremities;
• The presence of cardiovascular disease (CVD): symptoms of unstable angina, myocarditis, heart disease, heart failure;
• History of prior cancer;
• Healing of duodenal or gastric ulcers in history;
• Diabetes
• Severe chronic liver diseases or kidney disease in history;
• History of alcohol or other drug abuse;
• Pregnanсy;
• Any other physical diseases in decompensation or subcompensation,
• or those that are rated as severe or moderate;
• Therapeutic issues or psychiatric disorders of a patient which would
• make the subject unsuitable to participate in this study or to complete it;
• Participation in another clinical trial

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ALLO-ASCs; The patients receive ALLO-ADSCs. Biological is applied by surface application over perforated (1:3) autologous skin graft following the covering with hypoadhesive bandage. This procedure is carried out twice - once simultaneously with a skin grafting procedure and 2-3 days following autodermoplasty, while bandaging	Biological: ALLO-ASCs; 1). Cryopreserved cell suspension of early passages of cultured allogeneic MSCs isolated from SVF obtained from lipoaspirate, a total of 10 mln. of cultured cells; 2).The TE-construct consisting of collagen- or fibrin-derived hydrogels and cells of early passages (up to P5) suspension of allogeneic cultured MSCs isolated from SVF obtained from lipoaspirate; Biological is applied by surface application over perforated (1:3) autologous skin graft following the covering with hypoadhesive bandage. This procedure is carried out twice - once simultaneously with a skin grafting procedure and 2-3 days following autodermoplasty, while bandaging.; Other Names: Allogeneic adipose-derived stem cells
No Intervention: The standard treatment; All patients will be subjected to standard stepped treatment of burn wounds: Infusion therapy aimed to eliminate disorders of homeostasis during burn shock and burn toxemia;; Systemic antibiotic therapy for preventing infectious complications;; Adequate analgesia and sedation;; Decompression necrotomy in the first 24 hours following the burn trauma;; Necrectomy simultaneously with imposition of lyophilized xenografts performed in the first 1-5 days after applying burn;; Autologous skin grafting 3-5 days after performed xenografts with the perforation coefficient 1:3

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The degree of healing of skin flap; The degree of epithelialization of burn wounds in the perforations of a skin graft	The degree of healing of skin flap after autologous skin grafting;	up to 1 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The dynamics of healing of skin flap	Complete epithelization or epithelization more than 50% of the cells in the skin graft on the 10th day after autologous skin grafting are effective. The epithelialization less than 50% is not effective.	up to 1 month
Dynamics of the phagocytic activity of neutrophils in the area of burn wounds, according to NBT-test.	Dynamics of the phagocytic activity of neutrophils in the area of burn wounds, according to NBT-test.	up to 1 month
Duration of treatment (days) to complete epithelialization of burn wounds;	Duration of treatment (days) to complete epithelialization of burn wounds;	up to 1 month

Collaborators and Investigators

• Sponsor: A.A. Partners, LLC
• Investigators: Principal Investigator: Anatoliy V. Voronin, The head doctor of The Kyiv City Clinical Hospital №2; Principal Investigator: Georgiy P. Kozynets, MD, PhD, DSc, Head of the department of combustiology and plastic surgery, Shupyk National Medical Academy of Postgraduate Education

Publications and helpful links

General Publications

• Alexaki VI, Simantiraki D, Panayiotopoulou M, Rasouli O, Venihaki M, Castana O, Alexakis D, Kampa M, Stathopoulos EN, Castanas E. Adipose tissue-derived mesenchymal cells support skin reepithelialization through secretion of KGF-1 and PDGF-BB: comparison with dermal fibroblasts. Cell Transplant. 2012;21(11):2441-54. doi: 10.3727/096368912X637064. Epub 2012 Apr 10.

Helpful Links

• Adipose tissue-derived mesenchymal cells support skin reepithelialization through secretion of KGF-1 and PDGF-BB: comparison with dermal fibroblasts.
• 4. Alexaki V.-I. et al. Adipose tissue-derived mesenchymal cells support skin reepithelialization through secretion of KGF-1 and PDGF-BB: comparison with dermal fibroblasts. Cell Transplantation. 2012;21(11):2441-2454.

Study record dates

Study Major Dates

• Study Start (Actual): March 25, 2015
• Primary Completion (Anticipated): December 26, 2018
• Study Completion (Anticipated): December 26, 2018

Study Registration Dates

• First Submitted: March 31, 2017
• First Submitted That Met QC Criteria: April 10, 2017
• First Posted (Actual): April 14, 2017

Study Record Updates

• Last Update Posted (Actual): April 26, 2017
• Last Update Submitted That Met QC Criteria: April 25, 2017
• Last Verified: April 1, 2017

More Information

Terms related to this study

• Keywords: wound healing; regeneration; repair; burn wounds; Allogeneic adipose-derived stem cells; skin tissue engineering
• Additional Relevant MeSH Terms: Wounds and Injuries; Burns
• Other Study ID Numbers: MSC-P1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No