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Trial registered on ANZCTR

Registration number

ACTRN12615000366550

Ethics application status

Approved

Date submitted

22/01/2015

Date registered

22/04/2015

Date last updated

9/08/2018

Type of registration

Prospectively registered

Titles & IDs

Public title

Laser therapy in pressure ulcers: healing mechanisms

Scientific title

Effect of laser irradiation at different wavelengths (940, 808, and 658 nm) on healing mechanisms in human pressure ulcers

Secondary ID [1]

Nil

Universal Trial Number (UTN)

Trial acronym

Linked study record

Health condition

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

Pressure ulcers

Chronic wound healing

Condition category

Condition code

Physical Medicine / Rehabilitation

Other physical medicine / rehabilitation

Skin

Other skin conditions

Inflammatory and Immune System

Normal development and function of the immune system

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

The aim of this clinical research will be to assess the effect of laser irradiation at different wavelengths (940, 808, and 658 nm) on the healing mechanisms in human pressure ulcers.

Intervention:
Patients with pressure ulcers from groups A, B and C will receive laser therapy once daily, 5 times per week for 1 month. The equipment will be a gallium-aluminum-arsenide (GaAlAs) diode laser with an output power of 50 mW and continuous radiation emission at separate wavelengths of 940 nm (group A), 808 nm (group B) and 658 nm (group C). The spot size will be 0.1 cm2. The laser will be wired to a cone-shaped applicator (scanner). The duration of a single procedure will be relative to the wound size; the therapy will be adjusted to obtain an average dose of 4 J/cm2 (direct dose measured on a surface of the wound). In group D, the placebo group, a laser will be applied in the same manner, but the device will be turned off during the treatment sessions (only the applicator will be turned on to scan ulcers using non-coherent red visible light).

Intervention code [1]

Treatment: Devices

Comparator / control treatment

Single blind placebo (sham laser irradiation)

Control group

Placebo

Outcomes

Primary outcome [1]

Immunocytochemical and pathological analysis of the biological material from the wound is to observe tissue parameter changes under the influence of laser stimulations.

Outcomes include:
1. Quantitative analysis of the factors influencing the angiogenesis processes, endothelial cell proliferation and cell death (apoptosis) and immunocytochemical analysis of microvasculature density, as an indicator of angiogenesis process.

Tools/tests used:
ELISA test, fluorescence microscope capillaroscopy

Timepoint [1]

After one month therapy

Primary outcome [2]

The overall objective of the in vitro testing is the analysis of biological activity of fibroblasts in primary bacterial culture, derived from the wounds, under the influence of laser stimulations.

Outcome include:
1. The assessment of viability and proliferative capacity of cells and apoptosis after laser stimulation with the analysis of the level of fibroblast growth factor and the degree of fibroblasts transformation into myofibroblasts.

Tools/tests used:
serum assay, TUNEL technique

Timepoint [2]

After one month therapy

Primary outcome [3]

The overall objective of the biochemical examination of blood serum and plasma is to observe a changes of the inflammatory response under the influence of laser stimulations.

Outcome include:
1. The assessment of inflammatory markers and coagulation factors which play an important role in the molecular mechanism of inflammatory and proliferation phase of the wound healing process.

Tools/tests used:
ELISA test

Timepoint [3]

After one month therapy

Secondary outcome [1]

The overall objective of bacteriological examination of biological material from the wound is the analysis of qualitative and quantitative changes in bacterial biofilm under the influence of laser stimulations.

Outcome include:
1. Qualitative analysis of bacterial wound biofilm, taking into account each of the bacteria strains having a direct impact on healing disturbances or increasing risk of inflammatory reactions with the analysis of possible bacteriostatic or antibacterial effect within the wound.

Tools/tests used:
serum assay, Gram technique, cytokine assay

Timepoint [1]

After one month therapy

Eligibility

Key inclusion criteria

Participating subjects will meet the following inclusion criteria: (1) presented with a lower extremity pressure ulcer and (2) provided written informed consent to participate in the study. There will be no restrictions on gender, race, age, or ulcer duration.

Minimum age

18 Years

Maximum age

No limit

Sex

Both males and females

Can healthy volunteers participate?

Key exclusion criteria

Subjects with the following conditions will not be allowed to participate or will be excluded from the study: (1) clinically detectable infection in the ulcer (critical colonization of bacteria, no signs of healing for two weeks, friable granulation tissue, foul odor, increased pain in the ulcer, increased heat in the tissue around the ulcer, an ominous change in the nature of the wound drainage, e.g., new onset of bloody drainage or purulent drainage, or necrotic tissue in the ulcer); (2) use of drugs, such as corticosteroids, that could interfere with the wound-healing process; (3) use of special dressings, such as hydrocolloids, calcium alginate, activated carbon or any type of therapeutic procedure different from that used routinely by all groups in the study; (4) non-attendance to the therapeutic program; (5) pregnancy; (6) ankle-brachial pressure index (ABPI)<0.8; (7) diabetes mellitus; (8) systemic sclerosis; (9) cancer diagnosis; and (10) pareses and paralysis caused by injuries to the central or peripheral nervous system. Patients whose pressure ulcers required surgical intervention will also be excluded from the study.

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)

Participants will be randomly allocated to the groups. Computer-generated random numbers will be sealed in sequentially numbered envelopes, and the group allocation be independent of the time and person delivering the treatment. The physician (research coordinator) who will allocate the subjects to groups have envelopes, each containing a piece of paper marked with either group A, B, C or D. The physician will select and open an envelope in the presence of a physiotherapist to see the symbol and then direct the patient to the corresponding group.

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

Simple randomisation using computer and numbered envelopes

Masking / blinding

Blinded (masking used)

Who is / are masked / blinded?

The people receiving the treatment/s

Intervention assignment

Parallel

Other design features

Phase

Not Applicable

Type of endpoint/s

Efficacy

Statistical methods / analysis

Analysis and evaluation of the results will be based on the comparison of intra- and intergroup results. Statistical analysis of these results will be performed by means of the Statistica 10 software, manufactured by StatSoft (licence of Academy School of Physical Education). All analysed intergroup variables will be checked with respect to their similarity (uniformity; chi2 NW). A critical significance level a (alpha) = 0.05 or less will be considered statistically significant. For measurable variables (quantitative), arithmetic mean, standard deviations, medians and range of variability (extreme values) will be calculated. For qualitative variables, the frequency of occurrence (percentage) will be calculated. Comparison of intergroup results in order to determine the significance of the achieved differences, will be performed by means of parametric (ANOVA, Student's t-test, Welch's t test) or non-parametric (Mann-Whitney`s and Fischer tests, depending on meeting criteria for the specific test. Correlation of variables in the examined groups will also be checked.

To achieve study objectives the absolute minimal number of participants should be 15 in each group (for non-parametric tests). Smaller number of patients will not be enough from both statistical and clinical point of view (the smaller number of patients is not enough for reliable statistical analysis because of too large standard deviations due to characteristics of patients). However, the most reliable number od patients should be 30 in each comparative group (we will be able to use parametric tests). The reliable number of participants was estimated by Statistica 10 software, manufactured by StatSoft.

In calculating our sample size we have allowed for:
1. 30% loss of participants (exclusion criteria)
2. Historical information from our unit that 45% of patients who are offered conservative (standard physical therapy) management for this condition opt for laser therapy within 6 months.

This investigation has 95% power to detect a difference between group mean (SD) in the primary and secondary outcomes of 10 patients.

Recruitment

Recruitment status

Completed

Date of first participant enrolment

Anticipated

27/04/2015

Actual

27/04/2015

Date of last participant enrolment

Anticipated

Actual

14/05/2018

Date of last data collection

Anticipated

Actual

11/06/2018

Sample size

Target

120

Accrual to date

Final

120

Recruitment outside Australia

Country [1]

Poland

State/province [1]

Funding & Sponsors

Funding source category [1]

Charities/Societies/Foundations

Name [1]

European Pressure Ulcer Advisory Panel (EPUAP)

Address [1]

Clinical Trials Research Unit,
University of Leeds
Leeds LS2 9JT

Country [1]

United Kingdom

Funding source category [2]

Charities/Societies/Foundations

Name [2]

Polish Society of Lymphology

Address [2]

Pawla Street 9
41-500 Chorzow

Country [2]

Poland

Primary sponsor type

Individual

Name

Prof. Jakub Taradaj

Address

Department of Physiotherapy Basics
Academy School of Physical Education
Mikolowska Street 72A 40-065 Katowice

Country

Poland

Secondary sponsor category [1]

Individual

Name [1]

Prof. Dimitri Beeckman

Address [1]

University Centre for Nursing and Midwifery
Ghent University
De Pintelaan 185 5K3 B-9000 Ghent

Country [1]

Belgium

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

The Research Ethics Commitee from the Academy of Physical Education in Katowice, Poland

Ethics committee address [1]

Mikolowska Street 72 A
40-065 Katowice, Poland

Ethics committee country [1]

Poland

Date submitted for ethics approval [1]

02/04/2014

Approval date [1]

15/05/2014

Ethics approval number [1]

4/2014

Summary

Brief summary

Laser therapy has been used to accelerate wound healing for over forty years, but its results are still controversial. The European Pressure Ulcer Advisory Panel (EPUAP), National Pressure Ulcer Advisory Panel (NPUAP) and Pan Pacific Pressure Injury Alliance published an international guideline, “Prevention and Treatment of Pressure Ulcers: Clinical Practice Guideline”, in 2014. According to the guideline (content titled “Biophysical agents in pressure ulcer treatment”), several forms of energy have been studied for healing pressure ulcers. These include acoustic, mechanical, and kinetic energy, as well as energy from the electromagnetic spectrum (EMS). Infrared (thermal) radiation and ultraviolet light (invisible light) are all part of the EMS, as is electrical/electromagnetic stimulation. The recommendation for biophysical agents is supported by direct scientific evidence from properly designed and implemented clinical studies on pressure ulcers in humans, providing statistical results that consistently support the recommendation. One of the proposed physical methods in this document is laser irradiation, but the guideline stated that due to current insufficiency of evidence to suport or refute the use of laser therapy in the treatment of pressure ulcers. Laser therapy is not recommended for routine use at this time. The strength of evidence is only classified for C grade (supported by indirect evidence and/or expert opinion).
The results of our clinical study (Taradaj et al. “Effect of Laser Irradiation at Different Wavelengths 940, 808, and 658 nm on Pressure Ulcer Healing: Results from a Clinical Study” Evid Based Complement Alternat Med. 2013; 960240: 1-8) showed that the wavelength of the laser beam is extremely important during the wound-healing process (and perhaps this is one reason for the many controversies). In this trial, we found no evidence that justifies using laser therapy at wavelengths of 940 and 808 nm as an adjuvant to the future consensus pressure ulcer treatment. However, in our opinion the wavelength of 658 nm is interesting, and its use yielded in promising clinical results. We cannot agree with a general statement that laser therapy does not accelerate the healing process because the correct parameter settings (wavelength, dose, and method of application) must still be demonstrated in the literature. Future in vitro, animal and clinical studies are necessary, because in literature it is still unknown which processes occur at the cell or tissue level after laser irradiation. The aim of the following study will be collecting the biological material from the wound by biopsy and analysis of angiogenesis, cytometric meausrement of microvasculature density, cell apoptosis, fibroblast activity and collagen concentration, bacteriological and immunology examination.

Trial website

Trial related presentations / publications

Public notes

Contacts

Principal investigator

Name

Prof Jakub Taradaj

Address

Department of Physiotherapy Basics, Academy School of Physical Education, Mikolowska 72 Street 40-065 Katowice

Country

Poland

Phone

+48668613945

Fax

j.taradaj@awf.katowice.pl

Contact person for public queries

Name

Jakub Taradaj

Address

Department of Physiotherapy Basics, Academy School of Physical Education, Mikolowska 72 Street 40-065 Katowice

Country

Poland

Phone

+48668613945

Fax

j.taradaj@awf.katowice.pl

Contact person for scientific queries

Name

Jakub Taradaj

Address

Department of Physiotherapy Basics, Academy School of Physical Education, Mikolowska 72 Street 40-065 Katowice

Country

Poland

Phone

+48668613945

Fax

j.taradaj@awf.katowice.pl

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	Effect of laser therapy on expression of angio-and fibrogenic factors, and cytokine concentrations during the healing process of human pressure ulcers.	2018	https://dx.doi.org/10.7150/ijms.25651

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

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