The role of electrical stimulation and skin substitute in enhancing wound healing
| ISRCTN | ISRCTN18326338 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN18326338 |
| ClinicalTrials.gov number | Nil known. |
| Secondary identifying numbers | UREC 2020-9176-14934 |
- Submission date
- 18/08/2021
- Registration date
- 20/08/2021
- Last edited
- 07/06/2022
- Recruitment status
- Stopped
- Overall study status
- Stopped
- Condition category
- Skin and Connective Tissue Diseases
Plain English summary of protocol
Background and study aims
Skin is the largest human organ. It forms an essential barrier between the inside of our body and the environment. A wound is formed when there is a break in the skin. Wound healing is crucial to quickly restore skin integrity so that infection is prevented and internal functions can recommence.
The normal undamaged skin cells and tissue in your body possess very small electrical charges. These charges change when an injury breaks the skin’s surface and are thought to be very important in helping the body to start the right biological processes in order for the wound to heal quickly. Many scientists have used electrical stimulation safely to encourage the different parts of the healing process in different body tissues for many years.
Additionally, bioengineered “Skin Substitutes” are the most recent development which have shown great promise in wound healing. They are processed to create a material that can be applied to a wound. There is growing evidence from clinical trials that these skin substitutes can speed up healing in chronic wounds including leg ulcers and burns which are often slow to respond to standard dressing treatments. However, there is minimal information about their effect when applied to acute wounds in people who have normal healing abilities.
In view of the positive effects of electrical stimulation and the use of skin substitutes in the treatment of cutaneous wounds, we would like to investigate if the effect of electrical stimulation accelerates the integration of the skin substitutes in normal wounds to speed up wound healing.
Who can participate?
Healthy volunteers aged over 18 years
What does the study involve?
• The total duration of the trial is 28 days.
• Following successful screening, you will sign a consent form
• After the initial appointment on day 0, participants will attend on day 3, day 7, day 10, day 14, day 17, day 21, day 24 and day 28.
• At each visit, non-invasive measurements will be taken to assess the wound/scar using handheld probes, and photographs will also be taken
• On the first visit (day 0) 4 biopsies will be taken from the left arm in order to create the wounds/scars
• On Day 7, 5 mm biopsies will be taken over two of the wounds and scars so that they can be used to analyse healing at that time point. On day 14, a further two 5mm biopsies will be taken over the top of the remaining two scars on that arm. This process will then be repeated on the right arm starting on day 14 and this will continue to day 28.
• Participants will receive Placebo ES dressings and ES dressings and they will be applied to each arm depending upon randomisation.
• Skin substitute will be applied to two of the wounds on each arm on day 0 for the left arm and on day 14 on the right arm.
What are the possible benefits and risks of participating?
There are no direct benefits to participants in this study. Participants are carefully screened so that risks to them taking part (i.e. allergies to any of the topicals or local anaesthetic/dressings) are minimised. The main risk is that the wound site may bleed after the procedure and may feel a tender. As with any invasive procedure there is also a low risk that the site may become infected. We take precautions to ensure that the wound is clean and apply pressure and a special dressing to the wound to stop any bleeding. They are however left with a scar, which may take time to fade.
Where is the study run from?
Manchester University NHS Foundation Trust (UK) Wythenshawe Hospital Site
When is the study starting and how long is it expected to run for?
November 2019 to December 2022
Who is funding the study?
Accel‑Heal® Technologies Ltd (UK)
Who is the main contact?
Ardeshir Bayat, ardeshir.bayat@manchester.ac.uk
Sara Ud-Din, sara.ud-din@manchester.ac.uk
Contact information
Scientific
Division of Musculoskeletal and Dermatological Sciences
Manchester Academic Health Science Centre
University of Manchester
Stopford Building
Oxford Road
Manchester
Manchester
M13 9PT
United Kingdom
 ORCID ID |
0000-0002-4116-6491 |
|---|---|
| Phone | +441613060663 |
| ardeshir.bayat@manchester.ac.uk |
Study information
| Study design | Interventional single centre double-blind randomized controlled trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use contact details to request a participant information sheet. |
| Scientific title | Role of electrical stimulation in enhancement of cutaneous wound healing and engraftment: Accelerated healing by secondary intention and dermal substitute-assisted tissue regeneration in cutaneous wounds |
| Study objectives | To assess the effectiveness of electrical stimulation in accelerating cutaneous healing & integration of a skin substitute in acute wounds compared to “normal” unassisted cutaneous wound healing. |
| Ethics approval(s) | Approved 21/04/2020, University Research Ethics Committee 2 (2nd Floor Christie Building, The University of Manchester, Oxford Road, Manchester, M13 9PL, UK; +44 (0)161 306 6000; research.ethics@manchester.ac.uk), ref: 2020-9176-14934 |
| Health condition(s) or problem(s) studied | Assessment of cutaneous wound healing in healthy volunteers with and without skin substitute using electrical stimulation |
| Intervention | Participants are screened, consented and recruited. Participants receive 4 x 4mm punch biopsies to both upper inner arms to create the wounds. They are independently randomised as to which arm should receive either treatment or placebo. Allocation to arm will be by a computer-generated randomised block method. This allocation list will be held by a University of Manchester person independent of the study team. The participants will either have Active ES treatment on their Left or Right arms and this will be randomised to account for handedness. Both participants and researcher will be blinded as to which treatment is on which arm. Both Placebo/Sham device and Active ES device will look exactly the same. A member outside of the immediate research team will label the devices according to participant number on the randomisation list and the researcher will use these coded devices. Treatment: Electrical stimulation dressing Placebo: Sham electrical stimulation dressing Two wound sites will have dermal substitute applied and two left without. Wounds will be re-biopsied with 5mm punch biopsies at day 7 and day 14. Non-invasive measurements are taken on a weekly basis for each participants' duration of the trial. Final scar biopsies are used for histological, gene and protein analysis. |
| Intervention type | Procedure/Surgery |
| Primary outcome measure | 1. Assessment of cutaneous wound healing using histological and immunohistochemical and gene studies at day 0, day 7 and day 14 (angiogenesis, inflammatory and neurogenic markers). 2. Wound closure measured by non-invasive devices including 3-dimensional imaging at days 0, 3, 7, 10 and 14 and laboratory analysis including wound contraction markers such as alpha smooth muscle actin measured at days 0, 7 and 14. 3. Angiogenesis measured by non-invasive devices including full-field laser perfusion imaging and dynamic optical coherence tomography at days 0, 3, 7, 10, 14 and protein and gene markers including CD31 and VEGFA on days 0, 7 and 14. 4. Inflammation and neurogenic markers measured by immunohistochemical analysis and QRTPCR on days 0, 7 and 14. |
| Secondary outcome measures | 1. Assessment of cutaneous healing using objective non-invasive measurements on both arms on days 0, 3, 7, 10 and 14. 2. Wound elasticity (measured by elastometer) on days 0, 3, 7, 10 and 14. Skin colour (measured by colormeter) on days 0, 3, 7, 10 and 14. 3. Transepidermal water loss (measured by TEWL device) on days 0, 3, 7, 10 and 14. 4. Hydration (measured by hydration probe) on days 0, 3, 7, 10 and 14. Collagen (measured by SIAscopy) on days 0, 3, 7, 10 and 14. 5. Subjective scoring using VAS for pain, itch on days 0, 3, 7 , 10 and 14 for both arms. |
| Overall study start date | 01/11/2019 |
| Completion date | 01/12/2022 |
| Reason abandoned (if study stopped) | This trial was closed following discussions with the sponsors and University due to slow recruitment rate and the departure of the Principal Investigator. |
Eligibility
| Participant type(s) | Healthy volunteer |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | 20 |
| Key inclusion criteria | 1. Male and female subjects will be included to allow for gender demographic analysis. 2. Subjects of either gender who are 18 years and older. 3. Subjects who in the opinion of the investigator, are able to fully understand the study requirements and attend all follow-up visits. 4. Subjects must provide written informed consent to participate in the study. 5. Subjects weighing between 40 and 150kg, with a body mass index of 20-35kg/m2 (as described in the Quetelet’sindexQuetelet’s index – weight (kg)/height²(m)). |
| Key exclusion criteria | 1. Subjects who do not give consent or withdraw their consent to take part in the study. 2. Subjects of either gender who are less than 18 years old. 3. Subjects who have a history of keloid scarring. 4. Subjects who are pregnant or planning to conceive in the next 3 months. 5. Subjects who have a chronic or active skin disorder which may be considered to adversely affect the healing rate of the acute wound by the investigator. 6. Subjects with any likely wound healing impairment due to a clinically significant medical condition such as renal, hepatic, haematological, neurological or immune disease, including: 7. Rheumatoid arthritis 8. Chronic renal impairment 9. Diabetes Mellitus 10. Significant hepatic impairment 11. Inadequately or uncontrolled congestive heart failure 12. Malignancy – diagnosed or treated within the past 5 years. 13. Immunosuppressive, radiation or chemotherapy within the last three months. 14. Subjects who take medication known to alter/influence the healing of skin (e.g. steroids) 15. Subjects who are receiving formal oral anticoagulant therapy (warfarin). 16. Subjects who have received any investigational drugs, or have taken any in the previous month prior to day 0. 17. Subjects who have evidence of drug abuse. 18. Subjects who have had or are known to have hepatitis B or hepatitis C infection including carriers of hepatitis B surface antigen, hepatitis B core antibodies or hepatitis C antibodies. Previous vaccination against hepatitis B or C is not excluded. 19. Subjects who have previously had a positive result to the HIV antibody test, or admit to belong to a high risk group. 20. Any subject, who in the opinion of the investigator is unable to fully understand the requirements of the trial, consent or is unable to return for follow-up visits and complete the trial. 21. Subjects who become systemically unwell during the research process due to external study causes. 22. Subjects who have been involved in other studies in the past month prior to day 0 must discuss the exact details of the previous studies prior to a decision being made on eligibility for inclusion in this trial. 23. Subjects with known severe allergies to antibiotics as the skin substitutes may contain antibiotic residuals from processing. 24. Patients who are allergic to other amide local anaesthetics. 25. Previous MRSA colonisation or infection 26. Any bleeding disorders 27. Subjects with any heart conditions 28. Subjects who have a pacemaker inserted 29. Subjects who have epilepsy 30. Subjects who currently have cancer |
| Date of first enrolment | 01/09/2021 |
| Date of final enrolment | 01/09/2022 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centre
Southmoor Road
Wythenshawe
Manchester
M23 9LT
United Kingdom
Sponsor information
Industry
Hever Business Centre
Hever
TN8 7ER
United Kingdom
| Phone | +44 (0)1959 569 433 |
|---|---|
| jwootten@accelheal.com |
Funders
Funder type
Industry
No information available
Results and Publications
| Intention to publish date | 01/12/2022 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | Planned publication in high-impact peer reviewed journal. |
| IPD sharing plan | The datasets generated during and/or analysed during the current study will be available upon request. |
Editorial Notes
07/06/2022: The study status has been changed to 'Stopped'. REcruitment to the study did not begin.
19/08/2021: Trial's existence confirmed by University of Manchester.
