Assessment of the safety of a 'medieval antibiotic' used to treat infected diabetic ulcers on the skin of healthy non-diabetic volunteers
| ISRCTN | ISRCTN10773579 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN10773579 |
| IRAS number | 277243 |
| Secondary identifying numbers | IRAS 277243 |
- Submission date
- 05/01/2021
- Registration date
- 08/01/2021
- Last edited
- 24/11/2022
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Infections and Infestations
Plain English summary of protocol
Background and study aims
Infections that are resistant to antibiotics are a significant threat to human health. People with diabetes are especially vulnerable because they can develop long-lived, infected ulcers on their legs and feet. Diabetic ulcers often don’t respond to current antibiotics, and there are very few new antibiotics in development.
Most antibiotics are made from natural materials, and research into traditional infection remedies has produced some important treatments. For example, antibacterial dressings made with honey are routinely used in the NHS. The study team have studied many different infection remedies found in medieval medical manuscripts, to discover whether any of them could potentially reveal new sources of antibiotics.
The study team discovered a remedy used in medieval England to treat eye infections. This 'ancientbiotic' is made from garlic, onion, bile salts, and wine. This cocktail has been found to have a remarkable ability to kill many of the bacteria that cause antibiotic-resistant ulcer infection. It also has a promising safety profile in laboratory tests using human cells, an industry-standard model of eye irritation, and a mouse model of wound healing. The study team are exploring whether the ancientbiotic could be developed into a new treatment for diabetic ulcers, to prevent or cure bacterial infection.
The study team would like to test this liquid on healthy volunteers to see if it is safe to apply to healthy human skin. This is very similar to a patch test done to test for allergies. This will be done before the liquid can be tested on people with infections.
Who can participate?
Anyone aged from 18 to 79 years is invited to take part. People who are pregnant, have diabetes, asthma, sensitive skin, eczema, psoriasis, or are allergic to plasters or garlic (or other foodstuffs), or have broken skin on their upper arms should not take part. If you have any symptoms of COVID-19, or are self-isolating due to COVID-19 exposure, at the time of the study, you are also asked to not take part. Volunteers will be asked to wear a face-covering during study visits.
What does the study involve?
The study team will apply a drop of the liquid onto a sticking plaster, then apply this to the skin of the upper arm of volunteers. Volunteers will be asked to keep the plaster on, if possible, for two days.
After two days, volunteers will be asked to remove the plaster and let the study team know if there is any skin irritation. The study team will contact volunteers by phone, email, or by video-link (whichever is easiest for participants) to ask you some questions. This should take about 10 min. If participants have skin irritation, they will be asked to provide a digital photograph of the skin area on the arm (a mobile phone photo will be adequate). the study team will ask for volunteer permission and consent to store the image of the reaction to the liquid.
What are the possible benefits and risks of participating?
There is no direct benefit to participants from taking part. The findings of this study will help the study team develop and progress this research. It is hoped that there may be a benefit in the future for people with infections.
the study team do not expect any major risks from taking part. A disadvantage is the time participants will spend doing the study. There may be some risk of slight skin irritation from the liquid. There may be a slight smell of garlic too. The study team will ask participants to record any symptoms and will ask about these when they are in contact after 2 days.
Participants will be asked to come to a clinic at the Warwick Medical School for the liquid to be applied. This clinic will adhere to COVID-19 requirements to protect participants and the researchers (Participants will be required to wear a mask and only one person will be seen at a time at the clinic).
Where is the study run from?
University of Warwick (UK)
When is the study starting and how long is it expected to run for?
From September 2020 to October 2021. The exact start and ends dates for taking part will depend on the COVID-19 pandemic because changes in local and national restrictions will affect when the study team will be able to run the clinic.
Who is funding the study?
Diabetes UK (UK)
Who is the main contact?
Dr Freya Harrison
f.harrison@warwick.ac.uk
ancbio@warwick.ac.uk.
Contact information
Scientific
School of Life Sciences
Gibbet Hill Campus
Coventry
CV4 7AL
United Kingdom
| Phone | +442476524744 |
|---|---|
| F.Harrison@warwick.ac.uk |
Scientific
Warwick Clinical Trials Unit
Gibbet Hill Road
Coventry
CV4 7AL
United Kingdom
 ORCID ID |
0000-0002-8462-7999 |
|---|---|
| Phone | +44 (0)2476151128 |
| julie.bruce@warwick.ac.uk |
Public
School of Life Sciences
Gibbet Hill Campus
Coventry
CV4 7AL
United Kingdom
| Phone | +442476524744 |
|---|---|
| F.Harrison@warwick.ac.uk |
Study information
| Study design | Single centre, non-randomised, uncontrolled, Phase I pilot trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Non randomised study |
| Study setting(s) | Community |
| Study type | Treatment |
| Participant information sheet | ISRCTN10773579_PIS_v1.2_3Nov2020.pdf |
| Scientific title | Assessment of safety of a 'medieval antibiotic' to treat infected diabetic ulcers: a Phase 1 trial in healthy volunteers |
| Study objectives | The 'ancientbiotic' (made by combining garlic, onion, bovine bile and wine, and allowing the mixture to steep for nine days) will not result in irritation or inflammation in healthy, non-diabetic adults when it is applied topically to healthy skin for 48 h. |
| Ethics approval(s) | Approved 04/11/2020, University of Warwick Biomedical and Scientific Research Ethics Committee (Kirby Corner Road, Coventry, CV4 8UW; +44 (0)24 765 73961; BSREC@warwick.ac.uk), ref. BSREC 03/20-21 |
| Health condition(s) or problem(s) studied | Prevention/treatment of infection in diabetic foot and leg ulcers |
| Intervention | Sticking plaster infused with one drop of the liquid ancientbiotic preparation will be applied to the skin of the upper arm and worn for 48 h. Ancientbiotic preparation is equal amounts by volume of ground garlic bulb, ground onion bulb, white wine, and bovine bile, prepared under sterile conditions and left for 9 days, then passed through a 0.2 µm filter to ensure microbiological sterility. Participants will be contacted after 48 h by phone, email, or by video-link (whichever is easiest for participants), and asked to remove the plaster. Participants will be asked if they have experienced any adverse effects (AE), and if so, provide digital photographs of the affected area. A skin sample will be requested from 5 participants with no AEs. |
| Intervention type | Other |
| Primary outcome measure | 1. Adverse effects (AE) over 48 h measured using: 1.1. Participant questionnaire, where participants are asked to record the presence/absence of wound symptoms (erythema, spreading erythema, itch, discomfort, heat, pain, other adverse reactions) at 48 h 1.2. Digital photographs of the affected area where any suspected AE has occurred (to record the type, number, and spread/distribution of AEs) at 48 h 1.3. A skin sample (in 5 participants) from participants with no AEs at 48 h |
| Secondary outcome measures | There are no secondary outcome measures |
| Overall study start date | 07/09/2020 |
| Completion date | 31/10/2021 |
Eligibility
| Participant type(s) | Healthy volunteer |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | 100 |
| Total final enrolment | 109 |
| Key inclusion criteria | 1. Aged 18 to 79 years 2. Willing to provide signed consent to participate in the study 3. Fluent in spoken English to allow engagement with study 4. Willing to be contacted by telephone, email, or video-based platform at follow-up 5. Willing for the research team to hold a photographic image if any skin irritation occurs |
| Key exclusion criteria | 1. Pregnancy 2. Diabetes 3. Any known allergies or recent infection (within 3 months), including COVID-19 infection 4. Any skin condition, including eczema or psoriasis, or broken skin on the upper arms 5. Any diagnosis of asthma 6. Unable to be contacted by email, phone, or video platform within 48 h of intervention delivery |
| Date of first enrolment | 07/06/2021 |
| Date of final enrolment | 31/07/2021 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centres
University of Warwick
Coventry
CV4 7AL
United Kingdom
University of Warwick
Coventry
CV4 7AL
United Kingdom
Sponsor information
University/education
Deputy Director Research & Impact Services
University House
University of Warwick
Coventry
CV4 8UW
England
United Kingdom
| Phone | +44 (0)2476 575732 |
|---|---|
| C.D.Harris@warwick.ac.uk | |
| Website | http://www2.warwick.ac.uk/ |
"ROR" |
https://ror.org/01a77tt86 |
Funders
Funder type
Charity
Private sector organisation / Trusts, charities, foundations (both public and private)
- Alternative name(s)
- DIABETES UK LIMITED, British Diabetic Association
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 31/12/2022 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | Current publication and dissemination plan as of 24/11/2022: Results of the study have been published as a peer-reviewed research article: Bruce, J., Oyedemi, B., Parsons, N. et al. Phase 1 safety trial of a natural product cocktail with antibacterial activity in human volunteers. Sci Rep 12, 19656 (2022). https://doi.org/10.1038/s41598-022-22700-4 The article was published open access, in accordance with recommended guidance for transparent reporting, the Consolidated Standards of Reporting Trials (CONSORT) guidelines (https://www.consort-statement.org), the NIHR standard terms, and Warwick SOP 22: Publication & Dissemination. The results were also submitted to Diabetes UK as a project report. The results have been and will continue to be presented at national and international conferences. A lay summary will be produced for volunteers involved via the WMS website. Results will be publicised via the trial website and social media e.g. Twitter. Commercial outputs are not expected from this publicly funded trial, but intervention materials will be copyrighted as per institutional practice. HRA guidance on information for participants at the end of a trial will be followed: https://www.hra.nhs.uk/about-us/consultations/closed-consultations/guidance-participant-information-end-study-consultation/ Previous publication and dissemination plan: Results of the study will be prepared by the research team and submitted to Diabetes UK as a final report. Findings will be submitted to peer-reviewed journals and disseminated to the medical and exercise rehabilitation communities. Papers will be published in open-access journals, in accordance with recommended guidance for transparent reporting, the Consolidated Standards of Reporting Trials (CONSORT) guidelines (www.consort-statement.org), the NIHR standard terms, and Warwick SOP 22: Publication & Dissemination. Abstracts will be submitted to national and international conferences. A lay summary will be produced for volunteers involved via the WMS website. Results will be publicised via the trial website and social media e.g. Twitter. Commercial outputs are not expected from this publically funded trial, but intervention materials will be copyrighted as per institutional practice. HRA guidance on information for participants at the end of a trial will be followed: https://www.hra.nhs.uk/about-us/consultations/closed-consultations/guidance-participant-information-end-study-consultation/ |
| IPD sharing plan | Current IPD sharing statement as of 05/10/2021: Requests for anonymised trial data will be considered by the scientific team, after publication of trial results. Please contact Dr Freya Harrison (F.Harrison@warwick.ac.uk), for further information. Consideration will be given to reasonable requests for access to anonymised outcome data e.g. for the purposes of systematic review or meta-analyses. Previous IPD sharing statement: The datasets generated and/or analysed during the current study during this study will be included in the subsequent results publication |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Participant information sheet | version v1.2 | 03/11/2020 | 08/01/2021 | No | Yes |
| Protocol file | version 1.2 | 03/11/2020 | 10/08/2022 | No | No |
| Results article | 16/11/2022 | 18/11/2022 | Yes | No |
Additional files
- ISRCTN10773579_PIS_v1.2_3Nov2020.pdf
- Uploaded 08/01/2021
- 39230 Protocol V1.2 03Nov2020.pdf
Editorial Notes
24/11/2022: The publication and dissemination plan was updated.
18/11/2022: Publication reference added.
11/11/2022: The intention to publish date was changed from 31/10/2022 to 31/12/2022.
10/08/2022: Uploaded protocol (not peer-reviewed) as an additional file.
22/10/2021: Internal review.
05/10/2021: The following changes have been made:
1. The IPD sharing statement has been changed.
2. The participant level data has been changed from 'Other' to 'Available on request'.
08/09/2021: The following changes were made to the trial record:
1. The recruitment end date was changed from 30/09/2021 to 31/07/2021.
2. The total final enrolment was added.
11/05/2021: The recruitment start date was changed from 04/05/2021 to 07/06/2021.
23/02/2021: The sponsor email address was updated.
08/01/2021: The participant information sheet has been uploaded.
05/01/2021: Trial’s existence confirmed by University of Warwick Biomedical and Scientific Research Ethics Committee.
