Condition category
Infections and Infestations
Date applied
05/01/2021
Date assigned
08/01/2021
Last edited
08/01/2021
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Not yet recruiting

Plain English Summary

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.

Trial website

Contact information

Type

Scientific

Primary contact

Dr Freya Harrison

ORCID ID

Contact details

School of Life Sciences
Gibbet Hill Campus
Coventry
CV4 7AL
United Kingdom
+442476524744
F.Harrison@warwick.ac.uk

Type

Scientific

Additional contact

Prof Julie Bruce

ORCID ID

http://orcid.org/0000-0002-8462-7999

Contact details

Warwick Clinical Trials Unit
Gibbet Hill Road
Coventry
CV4 7AL
United Kingdom
+44 (0)2476151128
julie.bruce@warwick.ac.uk

Type

Public

Additional contact

Dr Freya Harrison

ORCID ID

Contact details

School of Life Sciences
Gibbet Hill Campus
Coventry
CV4 7AL
United Kingdom
+442476524744
F.Harrison@warwick.ac.uk

Additional identifiers

EudraCT number

Nil known

ClinicalTrials.gov number

Nil known

Protocol/serial number

IRAS 277243

Study information

Scientific title

Assessment of safety of a medieval antibiotic to treat infected diabetic ulcers: a Phase 1 trial in healthy volunteers

Acronym

Study hypothesis

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

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

Study design

Single centre, non-randomised, uncontrolled, Phase I pilot trial

Primary study design

Interventional

Secondary study design

Non randomised study

Trial setting

Community

Trial type

Treatment

Patient information sheet

See additional files

Condition

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 nine 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

Phase

Drug names

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 trial start date

07/09/2020

Overall trial end date

31/10/2021

Reason abandoned (if study stopped)

Eligibility

Participant 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

Participant type

Healthy volunteer

Age group

Adult

Gender

Both

Target number of participants

100

Participant 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

Recruitment start date

04/05/2021

Recruitment end date

30/09/2021

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Warwick Medical School
Gibbet Hill Campus University of Warwick
Coventry
CV4 7AL
United Kingdom

Trial participating centre

School of Life Sciences, University of Warwick
Gibbet Hill Campus University of Warwick
Coventry
CV4 7AL
United Kingdom

Sponsor information

Organisation

University of Warwick

Sponsor details

Deputy Director Research & Impact Services
University House
University of Warwick
Coventry
CV4 8UW
United Kingdom
+44 (0)2476 575732
jane.prewett@warwick.ac.uk

Sponsor type

University/education

Website

http://www2.warwick.ac.uk/

Funders

Funder type

Charity

Funder name

Diabetes UK

Alternative name(s)

Funding Body Type

private sector organisation

Funding Body Subtype

Other non-profit organizations

Location

United Kingdom

Results and Publications

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 statement:
The datasets generated and/or analysed during the current study during this study will be included in the subsequent results publication

Intention to publish date

31/10/2022

Participant level data

Other

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes

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.