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Trial registered on ANZCTR

Registration number

ACTRN12617000075381

Ethics application status

Approved

Date submitted

9/05/2015

Date registered

13/01/2017

Date last updated

1/02/2017

Type of registration

Prospectively registered

Titles & IDs

Public title

Effects of shock waves in the treatment of chronic wounds.

Scientific title

Clinical, pathomorphological, immunocytochemical and molecular characterization of the effects of extracorporeal shock waves (ESW) in patients with chronic wounds: a prospective, single-blinded, placebo-controlled, randomized clinical study with an in vivo and in vitro comparison.

Secondary ID [1]

None

Universal Trial Number (UTN)

Trial acronym

SHOWN - SHOck Waves in wouNds

Linked study record

Health condition

Health condition(s) or problem(s) studied:

chronic pressure ulcers

chronic diabetic ulcer

chronic venous ulcers

Condition category

Condition code

Physical Medicine / Rehabilitation

Physiotherapy

Skin

Dermatological conditions

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

ESW with a planar (electromagnetic) or radial (pneumatic) ESW applicator will be administered once to Group I, and three times to Group II at one session per week for three weeks. Methodology and parameters of the active ESW stimulation will be set in accordance to the literature data for clinical trials, as follows: energy flux density (EFD) of 0.10 mJ/mm2, pressure (P) of 2,5 bars, the number of pulses will be depended on the ulcer size, with basically 300 pulses plus additional 100 impulses/cm2 of wound area with a frequency (f) of 5 Hz (duration ranged of 10-15 minutes). In the placebo in vivo group, the sham-ESW stimulation will be made without the biologically active component with using the special polyethylene cover at the top of ESW applicator heading to absorb the energy and limit its propagation towards patient's tissue.

The in vitro single ESW stimulation will be performed with the same ESW applicators, as for an in vivo intervention. Methodology of the active ESW stimulation will be set in accordance to the literature data for in vitro studies. We are going to use a various combinations of ESW parameters to determine the mechanism of biological action and to show the distinct border between positive and harmful ESW effect, as follows: EFD of 0.10, 0,20 or 0,50 mJ/mm2, pressure (P) of 2,5, 3,5 or 5,0 bars, the number of different pulses number (100, 200, 300, 500, 5000) with frequency (f) of 1 or 5 Hz (duration ranged of 10-20 minutes). In the placebo in vitro group, the sham-ESW will be conducted and the cells will be not exposed to ESW, but will be maintained outside of the incubator with the device off but in contact with the plates for the same period of time.

Biopsies from the wounds will be obtained from all patients qualified into study. The resulting biopsies will be used in pathomorphological and immunocytochemical tests of wound tissues, and will provide sufficient material to develop primary cell cultures. On the other hand, the in vitro testing will be conducted on the basis of primary cultures of human skin fibroblasts obtained by biopsy before the ESW stimulation, from wound tissue.

Intervention code [1]

Rehabilitation

Intervention code [2]

Treatment: Devices

Comparator / control treatment

Placebo for both, in vivo and in vitro studies.

Control group

Placebo

Outcomes

Primary outcome [1]

First primary outcome is a clinical observation in vivo of size area of wound measured by digital planimetry, temperature distribution of wound measured by infrared thermal imaging camera, and pain intensity of wound assessed by Visual Analogue Scale.

Timepoint [1]

Immediately before and after ESW stimulation, as well as follow-up (2, 4 and 8 weeks).

Primary outcome [2]

Second primary outcome are a pathomorphological and immunocytochemical observations in vivo based on wound tissue biopsy samples: cell proliferation, apoptosis and necrosis assessed using TUNEL scratch assay; microvasculature and angiogenesis (PECAM-1, ICAM, Ki-67) by microscopic evaluation; mechanotransduction of biological signaling assessed using RT-PCR techniques; and reorganization of the cytoskeleton and nucleooskeleton by microscopic evaluation .

Timepoint [2]

Immediately before and after ESW stimulation, as well as follow-up (2, 4 and 8 weeks).

Secondary outcome [1]

Secondary outcome are immunocytochemical and molecular observations in vitro based on cultured reference fibroblast cells: fibroblast and keratinocytes migration and differentiation assessed by in vitro sensitization assay; cells proliferative activity and their apoptosis assessed using TUNEL scratch assay; analysis of tissues growth factors (FGF1 i FGF2, TGF-beta1 and CTGF) evaluated using enzyme-linked immunosorbent assay; cell transformation to myofibroblasts measured by in vitro scratch assay; transcriptional coactivators and mechanotransduction using RT-PCR techniques.

Timepoint [1]

Immediately before and after ESW stimulation.

Eligibility

Key inclusion criteria

1. Chronic wound (ChW) diagnosed as pressure, diabetic or venous etiology,
2. ChW surface area more than 3 cm2 of the ChW surface (due to do the biopsy) but less than 20 cm2 (to large area),
3. ChW duration more than 3 months (to be classified as a ChW), but less than 24 months (to be not classified as hard-to-heal),
4. ChW classified as 2nd grade (deep skin sore) or 3rd grade (the subcutaneous tissue damage with mild necrosis),
5. Obtain voluntary and informed consent of the patient to participate in the study.

Minimum age

18 Years

Maximum age

70 Years

Sex

Both males and females

Can healthy volunteers participate?

Key exclusion criteria

1. Acute wounds (surgical, traumatic, burns),
2. ChW size area less than 3 cm2 and more then 20 cm2,
3. ChW duration less than 3 months and more then 24 months,
4. ChW infection clinically confirmed,
5. ChW classified as 1st or 4th grade,
6. ChW with necrotic or infection events,
7. Contraindications for ESW stimulation (pregnancy or ovulation, cancer or malignancy, electronic or metal implants, acute or recurrent inflammations, bleeding tendency),
8. The lack of informed consent,
9. Failure to comply with the study protocol.

Study design

Purpose of the study

Treatment

Allocation to intervention

Randomised controlled trial

Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)

Allocation will be done by sealed opaque envelopes.

Methods used to generate the sequence in which subjects will be randomised (sequence generation)

Simple randomisation using a numbered envelopes.

Masking / blinding

Blinded (masking used)

Who is / are masked / blinded?

The people receiving the treatment/s

The people assessing the outcomes
The people analysing the results/data

Intervention assignment

Parallel

Other design features

Phase

Not Applicable

Type of endpoint/s

Safety/efficacy

Statistical methods / analysis

The obtained results will be subjected to statistical analysis made with the STATISTICA software. Power analysis in each group will be required and calculated to establish the statistical significance with a = 0.05 and power = 0.80 based on the estimated outcomes of 85% for ESW. For measurable variables, the arithmetic mean, standard deviation, medians and extreme values (minimum and maximum) will be calculated. However for qualitative variables, the occurrence rates, will be expressed as a percentage. Homogeneity of the compared groups will be established in terms of selected characteristics of the participants, and the level of significance will be accepted at p>0.05. Results will be compared between the two groups with comparative tests (independent), as well as each group results obtained before and after ESW stimulation (dependent tests). The type of statistical tests for both, in vivo and in vitro data, will be depend on the fulfilment of their objectives. Statistically significant differences at p<0.05.

Recruitment

Recruitment status

Not yet recruiting

Date of first participant enrolment

Anticipated

1/02/2017

Actual

Date of last participant enrolment

Anticipated

Actual

Date of last data collection

Anticipated

Actual

Sample size

Target

Accrual to date

Final

Recruitment outside Australia

Country [1]

Poland

State/province [1]

Lower Silesia

Funding & Sponsors

Funding source category [1]

University

Name [1]

Wroclaw Medical University

Address [1]

Pasteur 1 Street
50-367 Wroclaw

Country [1]

Poland

Primary sponsor type

University

Name

Foundation of the Wroclaw Medical University

Address

Mikulicza Radecki 5 Street
50-345 Wroclaw

Country

Poland

Secondary sponsor category [1]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Commission of Bioethics at the Wroclaw Medical University

Ethics committee address [1]

Pasteura 1 Street, 50-367 Wroclaw

Ethics committee country [1]

Poland

Date submitted for ethics approval [1]

21/11/2016

Approval date [1]

29/12/2016

Ethics approval number [1]

KB-632/2016

Summary

Brief summary

Chronic soft tissue wounds of the compression etiology are suffered by millions of people around the world, and the annual occurrence is steadily increasing. In the era of an ageing societies, They constitute a serious problem of the healthcare system for elderly people. Effective treatment strategies, for difficult to heal, chronic wounds of soft tissues, still are the significant interdisciplinary medical problem. This type of healthcare is a challenge for internal medicine, dermatology, traumatology, surgery, or angiology, but also for nurses and physiotherapists.
The scientific objective is an objective analysis of cellular and physiological mechanisms activated under the influence of ESW (Extracorporeal Shock Wave) within human chronic wounds. During the course of this project, a series of examinations will be carried out on cellular, histological and physical mechanisms associated with a complex and dynamic process of healing of chronic wounds (pressure ulcers). Authors of the project assume that the physical stimulus such as the ESW will bring significantly better treatment results as the effect of stimulating cellular and physiological mechanisms which promote regeneration and healing of pressure ulcers in combination with the effects obtained by placebo-controlled trials.
Simultaneously, there will be in vitro tests carried out on a cellular model of wound healing with a one-off ESW application. Tests will be conducted on primary cultures of fibroblasts and keratinocytes obtained from the wounds of patients and on the reference cell lines of these cells which represent the reference group. Appropriate in vitro test methods will be used to determine cell viability, proliferation index, cell death and cellular ageing, their ability of transformation into myofibroblasts and displacement within the cellular model of wound healing. The transduction phenomena of the mechanical signals of the ESW into cell signalling (mechanotransduction) will also be the subject of assessment. 
For these purposes will also be tested a proliferation, differentiation and transdifferentiation of cells involved in the regeneration of tissues at the cellular and molecular level comprising the examination of altered patterns of gene expression. Tests will be performed in the context of the registration of physiological and pathomorphological changes, which will be verified in the following stage by analyses on cells, genes expression and molecular tests. The whole in vivo study will be completed with in vitro tests on a cellular wound model, which fits into the model of a multi-faceted research project based on the principles of translational medicine.

Trial website

None.

Trial related presentations / publications

None.

Public notes

None.

Contacts

Principal investigator

Name

Dr Robert Dymarek

Address

Department of Nervous System Diseases, Wroclaw Medical University, Bartla 5 Street, 51-618 Wroclaw

Country

Poland

Phone

+48 723 895 770

Fax

r.dymarek@gmail.com

Contact person for public queries

Name

Robert Dymarek

Address

Department of Nervous System Diseases, Wroclaw Medical University, Bartla 5 Street, 51-618 Wroclaw

Country

Poland

Phone

+48 723 895 770

Fax

r.dymarek@gmail.com

Contact person for scientific queries

Name

Robert Dymarek

Address

Department of Nervous System Diseases, Wroclaw Medical University, Bartla 5 Street, 51-618 Wroclaw

Country

Poland

Phone

+48 723 895 770

Fax

r.dymarek@gmail.com

No information has been provided regarding IPD availability

What supporting documents are/will be available?

No Supporting Document Provided

Results publications and other study-related documents

Documents added manually

No documents have been uploaded by study researchers.

Documents added automatically

Source	Title	Year of Publication	DOI
Embase	The Immediate Clinical Effects Following a Single Radial Shock Wave Therapy in Pressure Ulcers: A Preliminary Randomized Controlled Trial of The SHOWN Project.	2023	https://dx.doi.org/10.1089/wound.2021.0015

N.B. These documents automatically identified may not have been verified by the study sponsor.

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Documents added manually

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