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Trial registered on ANZCTR

Registration number

ACTRN12615001281583

Ethics application status

Approved

Date submitted

24/08/2015

Date registered

24/11/2015

Date last updated

20/02/2017

Type of registration

Prospectively registered

Titles & IDs

Public title

The influence of cathodal and anodal electrical stimulation on skin blood flow and the healing of pressure ulcers

Scientific title

Evaluation of the effect of cathodal and anodal electrical stimulation on periwound skin blood flow and the healing of pressure ulcers in people with central nervous system injuries. A prospective, randomized, double-blind, controlled, clinical study

Secondary ID [1]

Nil known

Universal Trial Number (UTN)

Trial acronym

Linked study record

Health condition

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

Wound healing

Pressure ulcer

Chronic wound healing

Pressure ulcer healing

Spinal cord injury

Condition category

Condition code

Skin

Dermatological conditions

Physical Medicine / Rehabilitation

Other physical medicine / rehabilitation

Physical Medicine / Rehabilitation

Physiotherapy

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

Aim of study

The purpose of this prospective, parallel-group, randomized, double-blind, controlled, clinical trial is to compare the skin blood flow and healing progress of pressure ulcers (PU) in people with spinal cord injury after 8 weeks of intervention involving standard wound care (SWC), SWC in conjunction with high voltage monophasic pulsed current (HVMPC) delivered by the cathode, and SWC combined with HVMPC delivered by the anode as the treatment electrodes.

Demographic information on the patients will be compiled during standardized interviews and physical examinations, as well as from additional examinations of the patients and the documentation of their concomitant diseases.

The patients’ physical and mental conditions, activity, mobility and incontinence will be assessed using the Norton scale (a score < 14 indicated a high risk of PU development). To assess the possibility of friction and shear and wound moisture, as well as sensory perception of the patients, their physical activity and mobility the Braden Scale will be applied (a score < 16 pointed to a high risk of PU development). Patients’ nutritional status will be identified by means of the Nutritional Risk Score (NRS-2002).

Wound severity at enrolment will be assessed based on the National Pressure Ulcer Advisory Panel criteria: Category II ulcers = partial-thickness loss of the dermis presenting as a shallow open ulcer with a red pink wound bed, without slough; Category III ulcers = full-thickness tissue loss; subcutaneous fat may be visible but bone, tendon or muscle are not exposed; Category IV ulcers = full-thickness tissue loss with exposed tendon, muscle or bone. Slough or eschar may be present on some parts of the wound bed. Can include undermining and tunnelling.

SWC programme administered to all groups.

All patients will be treated to prevent the development of new PUs. Pressure-redistribution surfaces, devices and pillows will be applied as needed. A nurse or physiotherapist will reposition the immobile patients every 2 hours at the least.

Blood tests will be carried out to screen for nutritional status markers and metabolic disorders such as anaemia (iron deficiency anaemia or anaemia of chronic disease), thyroid dysfunction, impaired glycaemic control, dehydration, protein deficit, hypoalbuminemia.

Wounds will be regularly assessed by the attending physician over the period of the study to select topical treatments appropriately addressing moisture control, bacterial burden, and debridement needs; microbiological culture and sensitivity tests will also be performed.

A team formed of a physician, a nurse, a physical therapist and a dietician will make comprehensive, interdisciplinary assessments of the patients to develop SWC programmes meeting their specific demands, for instance consisting of nutritional intervention, optimization of the wound dressing protocol, and incontinence management. The clinician caregivers will be blinded to participant’s group.

Patients in all groups will receive similar standard topical care, selected to address their individual needs and to promote moist interactive healing.

All immobilized patients will receive low-molecular-weight heparin (enoxaparin) as a standard therapy. Patients with elevated leukocyte levels will be treated with antibiotics selected following microbiological culture and sensitivity testing of the PU swab.

Electrical stimulation with the cathode

In the cathode ES group, patients will be administered HVMPC in addition to SWC.

The device for applying HVMPC will be the Intelect Advanced Combo (by Chattanooga, USA). The device generates a twin-peak monophasic pulse consisting of two 77- microsecond exponential pulses in rapid succession (the twin-peak pulse duration was 154 microseconds). Pulse frequency will be 100 pps. Current intensity will be set within 0.25-0.40 A, so patients will only experience sensory effects (without motor reactions). Voltage will be set to 100 – 120 V. and the electrodes will deliver an electrical charge of 250- 500 microcoulomb per second. This HVMPC protocol has been selected because of the positive results of earlier clinical trials on patients with PUs and venous leg ulcers (VLUs).

Each patient will have their own set of electrodes made of conductive carbon rubber. The treatment electrode (of a size matching the wound surface area) will be placed on an aseptic gauze pad saturated with physiological saline overlaying the wound site. The dispersive electrode (bigger than the treatment electrode) closing the electrical circuit will be positioned at least 20 cm from the PU. Before and after each ES procedure, the electrodes will be sterilized in a disinfectant solution.

Over the period of the intervention, the negative electrode (cathode) will be used to treat PUs. The authors of some other clinical studies on PUs have also used cathodal stimulations.

In the experiment, five 50-minute sessions will be held per week (one a day), following the approach adopted by other authors.

PUs will be thoroughly cleansed with a 0.9% sodium chloride solution and covered with the earlier described dressings immediately after ES the procedure.

Electrical stimulation with the anode

Patients in the anodal ES group will receive HVMPC in the same way as patients in the cathodal ES group, but the treatment electrode will be the anode. The authors of other clinical studies on PUs used anodal stimulation.

HVMPC with the cathode (in the cathode ES group) and with the anode (in the anode ES group) will be applied for a period of 8 weeks (total of 40 HVPC sessions), during which wounds will be observed for healing progress.

Intervention code [1]

Rehabilitation

Intervention code [2]

Treatment: Devices

Intervention code [3]

Treatment: Other

Comparator / control treatment

Patients in the control group will be treated to prevent the development of new PUs. Pressure-redistribution surfaces, devices and pillows will be applied as needed. A nurse or physiotherapist will reposition the immobile patients every 2 hours at the least.

Blood tests will be carried out to screen for nutritional status markers and metabolic disorders such as anaemia (iron deficiency anaemia or anaemia of chronic disease), thyroid dysfunction, impaired glycaemic control, dehydration, protein deficit, hypoalbuminemia.

Wounds will be regularly assessed by the attending physician over the period of the study to select topical treatments appropriately addressing moisture control, bacterial burden, and debridement needs; microbiological culture and sensitivity tests will also be performed.

A team formed of a physician, a nurse, a physical therapist and a dietician will make comprehensive, interdisciplinary assessments of the patients to develop SWC programmes meeting their specific demands, for instance consisting of nutritional intervention, optimization of the wound dressing protocol, and incontinence management. The clinician caregivers will be blinded to participant’s group.

Patients will receive similar standard topical care, selected to address their individual needs and to promote moist interactive healing. All immobilized patients will receive low-molecular-weight heparin (enoxaparin) as a standard therapy. Patients with elevated leukocyte levels will be treated with antibiotics selected following microbiological culture and sensitivity testing of the PU swab.

In addition to standard wound care described above, the control group will also receive sham ES. The electrodes will be arranged in the same way as in the ES groups and all current parameters will also be displayed on the monitor, but the current itself will not be applied. Five 50-minute sessions of sham ES will be held per week (one a day).

Sham HVMPC will be applied for a period of 8 weeks (total of 40 sham HVMPC sessions), during which wounds will be observed for healing progress.

Control group

Placebo

Outcomes

Primary outcome [1]

Absolute average change in wound surface area (WSA) (cm2) after treatment in relation to its baseline in all groups (showing how effective treatment will be in particular groups)

WSA will be determined using the same method that was already employed in several previous clinical trials. First wound contours will be copied onto transparent film sheets. The contours will be then measured with the planimeter to establish the surface area of each wound. The obtained data will be processed by a digitizer (Mutoh Kurta XGT, Altek, USA) connected to a personal computer (C-GEO v. 4.0 Nadowski, PL) which will be also used to store the results. Measurement errors caused by different shapes of the wounds may range from 2.7% (for PUs of 60 to 70 cm2 in size) to 37.9% (for PUs < 1 cm2). The method with which measurement errors will be calculated can be found in our earlier study.

Timepoint [1]

At baseline and week 8

Primary outcome [2]

Changes in skin blood flow (SBF) around the wound after 2 and 4 weeks of treatment in relation to its baseline in all groups (to compare changes in SBF between the groups).
SBF will be measured using a laser Doppler imager (PERIFLUX 5000; Perimed; Sweden)

Timepoint [2]

At baseline, week 2, and week 4

Secondary outcome [1]

The percentage change/decrease in WSA after 4 weeks of intervention with SWC + sham ES, SWC + cathode HVMPC, and SWC + anode HVPC (to compare changes in PU surface area between the groups).

The formula for calculating 4 week percentage WSA reduction from baseline (PAR4) will be the following: PAR4 = initial WSA (cm2) – WSA (cm2) at week 4 x 100% / Initial WSA (cm2)

Timepoint [1]

At baseline, and week 4

Secondary outcome [2]

The percentage WSA reduction after 8 weeks of intervention with SWC + sham ES, SWC + cathode HVMPC, and SWC + anode HVPC (to compare changes in PU surface area between the groups).

The formula for calculating 8 week percentage WSA reduction from baseline (PAR8) will be the following: PAR8 = initial WSA (cm2) – WSA (cm2) at week 8 x 100% / Initial WSA (cm2)

Timepoint [2]

At baseline, and week 8

Secondary outcome [3]

The percentage of PUs the WSA of which will close. Wound closure will be assessed by treating physician using a wound measurement device.

Timepoint [3]

At week 8

Secondary outcome [4]

The percentage of PUs the WSA of which will increase (WSA greater than the baseline). The increase of WSA will be assessed by treating physician using a wound measurement device.

Timepoint [4]

At week 8

Secondary outcome [5]

The Gilman's parameter calculated to ensure the comparability of healing progress regardless of wound shape

The Gilman's parameter (GP) will be calculated as:

GP= S / p
S = (Si - Sf)
Si, Sf - initial and final wound surface areas
p = (pi + pf) / 2
pi, pf - initial and final wound perimeter

Timepoint [5]

At week 8

Eligibility

Key inclusion criteria

Patient eligibility for the experiment will be established by their physician as per the following criteria: a) spinal cord injury (SCI); b) brain injury (caused by stroke or mechanical injury); c) older than 18 years of age; d) hospitalized in a rehabilitation center; e) with Category II, III or IV PU of at least 0.5 cm2 in size and of duration of at least 4 weeks.

Minimum age

18 Years

Maximum age

No limit

Sex

Both males and females

Can healthy volunteers participate?

Key exclusion criteria

The patients who are not qualify for ES (cancer, electronic implants, malignant, tunneling and necrotic wounds, osteomyelitis, PU requiring surgical intervention) will be excluded from participating, as well as those with diagnoses that might interfere with wound healing, such as diabetes (HbA1C > 7%), venous insufficiency, critical infection.

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)

The selected patients (or their legal guardians) who will give their consent to participate in the study will be randomly assigned to the control group (SWC plus sham ES), the cathode HVMPC group (SWC plus cathode HVMPC) or the anode HVPC group (SWC plus anode HVMPC) using a concealed process.

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

Patient allocation to groups will be independent of when and who will deliver the treatment.

The group allocation sequence will be concealed. Simple randomisation with numbered envelopes will be used.

An independent person will receive three batches of 15 pieces of paper, each marked with a letter indicating to which group the patient should go, i.e. A for the SWC+cathodal HVMPC group, B for the SWC+anodal HVMPC group and C for the SWC+sham ES group.. The person, unaware of what the symbols mean, will insert the pieces of paper into 45 envelopes randomly drawn by the computer. The sealed envelopes will be transferred to the main investigator in charge of patients’ allocation to groups. Before the treatment, the envelopes will be opened one-by-one in the presence of a physiotherapist and the patient concerned will be directed to the appropriate study group.

Masking / blinding

Blinded (masking used)

Who is / are masked / blinded?

The people receiving the treatment/s
The people administering 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

Efficacy

Statistical methods / analysis

To determine group sizes for the experiment, a pilot study was carried out. Because the results obtained with the random pilot sample had unimodal distribution and skewness and flatness were smaller than 2.5, the arithmetic average and standard deviation were chosen for the experiment as good measures of central value and dispersion.

Based on type I error, probability a = 0.05 and test power 1-beta = 0.90 were accepted for the study. An assumption was made that to assess wound healing progress in each group, the minimum statistically significant difference would be set at 25% of the baseline. According to the assumptions, a group in the experiment should have at least 12 patients (36 patients in three groups), but the actual size of the sample will be increased to 45 randomly selected patients to allow for possible dropouts.

Because normality of distribution cannot be tested for a small sample (groups of 12 patients), statistical calculations will be performed using non-parametric tests. The intra-group comparisons will be made using Friedman’s ANOVA and the inter-group comparisons with the Kruskal-Wallis analysis of variance.

All patients in the experiment will be assessed for the homogeneity of distribution of their characteristics. The mean WSA before and after treatment will be compared within particular groups. The mean percentage change in periwound skin blood flow will be calculated (at weeks 2 and 4) and then an inter-group comparison will be performed. The mean percentage change in wound area, the value of the Gilman’s parameter will be calculated (at week 4) in all groups and then an inter-group comparison will be performed. At the end of intervention (week 4), the healing rates of PUs that have closed or worsened (i.e. having WSA greater than baseline) will be calculated and compared between the groups.

The level of statistical significance in all tests will be p < 0.05.

The statistical analysis will be performed using the Statistica software by StatSoft (licensed to the Medical University of Silesia).

Recruitment

Recruitment status

Completed

Date of first participant enrolment

Anticipated

1/12/2015

Actual

1/12/2015

Date of last participant enrolment

Anticipated

29/02/2016

Actual

8/08/2016

Date of last data collection

Anticipated

30/09/2016

Actual

30/09/2016

Sample size

Target

Accrual to date

Final

Recruitment outside Australia

Country [1]

Poland

State/province [1]

Silesia

Funding & Sponsors

Funding source category [1]

University

Name [1]

Academy of Physical Education

Address [1]

Department of Physical Therapy,
Mikolowska 72A street
40-065 Katowice

Country [1]

Poland

Primary sponsor type

University

Name

Academy of Physical Education

Address

Department of Physical Therapy,
Mikolowska 72A street
40-065 Katowice

Country

Poland

Secondary sponsor category [1]

None

Name [1]

Address [1]

Country [1]

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 72A street
40-065 Katowice

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

Clinical practice guidelines in Europe, the United States, and Canada recommend applying (ES) to chronic PUs resistant to standard wound care (SWC). However, the exact rules for applying ES to different-Category wounds are still to be developed and tested in clinical studies. It is though that the polarity of the treatment electrode used during ES procedures is significance for the healing process. 
Despite the specific rules for treating human wounds with the anode and the cathode not having been developed yet, the results of in vitro and in vivo studies indicate that both these electrodes can promote wound healing and that the polarity of the treatment electrode should match the wound healing stage.
According to the authors of in vitro studies, cells involved in tissue repair migrate toward the electric field created by the anode or the cathode. In cell cultures, the anode enhances the motility of macrophages and neutrophils, but human keratinocytes, fibroblasts and bovine corneal epithelial cells migrate directionally toward the cathode. The results of in vitro studies suggest that anodal stimulation is appropriate for increasing macrophage and phagocyte activity during the wound’s inflammatory phase, whereas cathodal stimulation can be effective in the proliferative phase of the wound healing process. 
The authors of in vivo experiments with animals concluded that anodal ES was appropriate as a means of improving the healing of acute skin wounds, because it caused the wound surface to close and the wound potential to return faster to the preinjury level. Borba’s randomized in vivo study with rats showed that anodal ES improved neoangiogenesis in the early stage of acute experimental wound healing. 
Clinical studies differ in which electrode is used as the treatment electrode. Some authors stimulate wounds with the anode and reverse polarity to negative only if healing progress is not satisfactory. In other studies, the cathode is applied for the length of treatment or for the first 1-3 weeks after which polarity is reversed every week or the anode is introduced for the remainder of treatment. 
Our experiment aims to expand the knowledge of how HVMPC delivered by, respectively, the cathode and the anode as the treatment electrodes contributes to the healing of Category II - IV PUs in people with spinal cord injury at high risk of PU development. In the experiment, cathodal and anodal HVPC will be applied to treat PUs and will be compared for effectiveness. 

Our study is specifically designed to test the following hypotheses:

1. Both cathodal and anodal HVMPC administrated as part of an interdisciplinary wound care programme improve the healing of Category II-IV PUs.

2. Cathodal HVMPC increases periwound skin blond flow and accelerates the healing of PUs more than anodal HVMPC does. 

Another purpose of the experiment is gain new knowledge about the efficacy of cathodal and anodal HVMPC in wound healing

Trial website

Trial related presentations / publications

n/a

Public notes

Contacts

Principal investigator

Name

Dr Anna Polak

Address

Department of Physical Therapy, Academy of Physical Education, Mikolowska 72A street, 40-065 Katowice

Country

Poland

Phone

+48322075129

Fax

[email protected]

Contact person for public queries

Name

Anna Polak

Address

Department of Physical Therapy, Academy of Physical Education, Mikolowska 72A street, 40-065 Katowice

Country

Poland

Phone

+48322075129

Fax

[email protected]

Contact person for scientific queries

Name

Anna Polak

Address

Department of Physical Therapy, Academy of Physical Education, Mikolowska 72A street, 40-065 Katowice

Country

Poland

Phone

+48322075129

Fax

[email protected]

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	A Randomized, Controlled Clinical Study to Assess the Effect of Anodal and Cathodal Electrical Stimulation on Periwound Skin Blood Flow and Pressure Ulcer Size Reduction in Persons with Neurological Injuries.	2018	https://dx.doi.org/10.25270/owm.2018.2.1029

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

Trial Review

Documents added manually

Documents added automatically