Plain English Summary
Background and study aims
Pneumococcus is a bacteria found in the nose. Small numbers of these bacteria are often found in the nose. Usually, the carrier does not know the bacteria are there. In most adults this is present at least once per year and more often in children. It could be that a small number of bacteria present in the nose (“nasal carriage”) can help to protect people against disease. Mild infections with pneumococcus are very common, such as ear infections in children. But pneumococcus can also infect the lung (causing pneumonia) or the brain (causing meningitis) or the blood (causing sepsis). These severe infections are very uncommon in healthy adults. Very young children and adults who are elderly or those who have other illnesses are more likely to become ill. In future we may be able to protect people against severe disease from pneumococcus using a vaccine. In order to develop a vaccine, there is a need to understand how the bacteria spread. This study looks at what happens when the hands of healthy volunteers are exposed to small numbers of the bacteria and they are asked to touch their noses. This aims to mimic the possible transmission route of this bacteria from people’s hands into their noses. The aim of this study is to determine the feasibility of Experimental Pneumococcal Carriage acquisition following pneumococcal transmission from hand to nostrils in order to reduce transmission.
Who can participate?
Healthy adults 18-50 years of age.
What does the study involve?
Participants are screened in order to see if they are suitable to participate. After signing consent, participants start the study, where they are administered a droplet of the bacteria on their hand or finger. Then they are asked to rub or poke their nose with their hand/finger. After this, participants are in contact with the researchers by phone for seven days. Participants attend the clinic at day two, six and nine where they provide samples from their nose. At the end of the study they are given medication to treat any bacteria if they are still carrying it.
What are the possible benefits and risks of participating?
Participants benefit from receiving financial compensation for their time and inconvenience. The risk from the tests performed in the study (such as blood tests and nasal/throat samples) is very low, as these tests are not expected to cause more than mild temporary discomfort. The study involves live bacteria, which can cause severe infection (such as pneumonia or meningitis) in people who are at high risk of infection. To minimize this risk, volunteers who are healthy and low-risk are carefully selected, and a detailed medical assessment is carried out on all potential volunteers before they start the study. In addition, a thermometer and antibiotics are provided to identify and treat infection early. The research team are available any time day or night and provide access to healthcare if required.
Where is the study run from?
Royal Liverpool University Hospital (UK)
When is the study starting and how long is it expected to run for?
March 2017-June 2017
Who is funding the study?
1. Medical Research Council (UK)
2. Unilever (UK)
Who is the main contact?
Dr Victoria Connor
Victoria.connor@lstmed.ac.uk
Trial website
Contact information
Type
Public
Primary contact
Dr Victoria Connor
ORCID ID
http://orcid.org/0000-0001-6741-8039
Contact details
Respiratory Infection Group
Department of Clinical Sciences
Liverpool School of Tropical Medicine
Pembroke Place
Liverpool
L3 5QA
United Kingdom
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
33503
Study information
Scientific title
Hand to nose transmission of streptococcus pneumoniae in healthy participants – pilot study
Acronym
Study hypothesis
The aim of this study is to determine the feasibility of Experimental Pneumococcal Carriage acquisition following pneumococcal transmission from hand to nostrils.
Ethics approval
North West - Liverpool East Research Ethics Committee, 02/02/2017, ref: 17/NW/0054
Study design
Observational; Design type: Cohort study
Primary study design
Observational
Secondary study design
Cohort study
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
Condition
Specialty: Infectious diseases and microbiology, Primary sub-specialty: Infection prevention; UKCRC code/ Disease: Infection/ Other infectious diseases
Intervention
Healthy non-smoking adult participant’s hands are exposed with well-characterised, fully sequenced penicillin-sensitive pneumococci in order to observe them for the development of pneumococcal carriage.
Initially participants are seen to discuss potential study involvement, consent obtained following time for participants to make a fully informed decision about volunteering.
After consent is received, during the week prior to the start of the study participants are screened and have baseline samples taken. This involves clinical examination and medical history, nasal wash sample collection, urine sample (pregnancy test for females), viral throat swab and blood test.
If participants are still eligible following screening they are seen a week later to start the study. The first official visit is pneumococcal exposure, where a droplet pneumococcal bacteria is administered to one hand or one finger. Participants are asked to actively attempt to facilitate transmission of pneumococci bacteria from hand to nose by either rubbing their nose (with exposed area) or by poking their nose (with exposed finger). This may be done while the bacteria is still wet or following drying time. Following this exposure day participants have daily telephone contact with a researcher (by telephone) for seven days for safety. They are also supplied a safety pack which includes thermometer for participants to take their temperatures each day for seven days, safety information leaflet and back up antibiotics if needed.
Participants attend the clinic two, six and nine days following this exposure where they undergo a nasal wash to obtain samples for analysis of nasal carriage of the bacteria. At the end of the study (day nine) we will advise participants to take three days of amoxicillin to clear carriage if they still are carrying the bacteria in their noses.
The total duration of the study (observation and follow-up) is three weeks, with a maximum of six visits (including consent visit).
Intervention type
Other
Phase
Drug names
Primary outcome measure
Primary outcome measure as of 17/09/2018:
1. Detection of 6B pneumococci is measured by using classical culture methods from nasal wash recovered from the participants at days two, six and nine.
2. Recruitment rate recorded as the number of eligible participants who consent to participate in the study by 6 months
3. To inform estimation of sample size for a future trial by measuring the colonization rates in one of the four transmission groups in a full cohort of participants
Previous primary outcome measure:
Detection of 6B pneumococci is measured by using classical culture methods from nasal wash recovered from the participants at days two, six and nine.
Secondary outcome measures
Secondary outcome measures as of 17/09/2018
1. Density and duration of pneumococcus carriage is measured using classical culture methods from nasal wash recovered at day 2, 6 and
2. Rate of pneumococcal carriage among participants who were expose to and attempted transmission following drying of the bacterial stock is measured using classical culture methods from nasal wash recovered at day two, six and nine
3. Rate of pneumococcal carriage among participants who were expose to and attempted transmission with wet bacteria stock is measured using classical culture methods from nasal wash recovered at day two, six and nine
4. Assessment of safety of the trial procedures
5. Assessment of any serious concerns about the acceptability of the interventions and feasibility of the trial procedures
Previous secondary outcome measures:
1. Density and duration of pneumococcus carriage is measured using classical culture methods from nasal wash recovered at day 2, 6 and 9
2. Rate of pneumococcal carriage among participants who were expose to and attempted transmission following drying of the bacterial stock is measured using classical culture methods from nasal wash recovered at day two, six and nine
3. Rate of pneumococcal carriage among participants who were expose to and attempted transmission with wet bacteria stock is measured using classical culture methods from nasal wash recovered at day two, six and nine
Overall trial start date
01/03/2017
Overall trial end date
01/06/2017
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Adults aged 18-50 years (chosen to minimise the risk of pneumococcal infection, and to allow comparison with previously published experimental work done by our group)
2. Fluent spoken English - to ensure a comprehensive understanding of the research project and their proposed involvement
3. Access to their own mobile telephone – to ensure safety and timely communication
4. Capacity to give informed consent
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
Planned Sample Size: 80; UK Sample Size: 80
Participant exclusion criteria
1. Previous pneumococcal vaccination
2. History of major pneumococcal illness
3. Close physical contact with at risk individuals (children under 5 years of age, immunosuppressed adults, elderly, chronic ill health) - minimise risk of pneumococcal transmission
4. Allergy to penicillin/amoxicillin
5. Any current treatment for asthma – confounding effect of medications such as corticosteroids, and propensity to infection
6. Any acute dermatological illness or skin injury affecting the hands or face- confounding effects of topical medications and propensity to infection
7. Taking daily medications that may affect the immune system e.g. steroids, steroid nasal spray, antibiotics and roacutanne.
8. Current illness, acute illness within 3 days prior to inoculation or antibiotic treatment within 2 weeks of inoculation
9. Pregnancy - minimise risk of pneumococcal disease
10. Diagnosed as diabetic
11. Involved in another clinical trial unless observational or in follow-up (non-interventional) phase.
12. Have been involved in a EHPC clinical trial involving pneumococcal inoculation in the last 3 years
13. History of drug or alcohol abuse
14. History of Smoking
15. Current regular smoker (smokes daily/ smokes > 5 cigarettes per week) - minimise risk of pneumococcal disease
16. Recent smoker i.e. within the last 6 months - minimise risk of pneumococcal disease
17. Ex-smoker with a significant smoking history (> 10 pack years) – minimise risk of pneumococcal disease
18. Unable to give fully informed consent
It is anticipated that 10-15% participants of screened participants will have natural pneumococcal colonisation at the time of recruitment as demonstrated by the initial nasal wash. These individuals will be excluded from the study after screening visits.
Recruitment start date
19/04/2017
Recruitment end date
19/05/2017
Locations
Countries of recruitment
United Kingdom
Trial participating centre
Royal Liverpool and Broadgreen University Hospitals
Clinical Research Unit
Royal Liverpool and Broadgreen University Hospitals
Prescott Street
Liverpool
L7 8XP
United Kingdom
Funders
Funder type
Government
Funder name
Medical Research Council
Alternative name(s)
MRC
Funding Body Type
government organisation
Funding Body Subtype
Federal/National Government
Location
United Kingdom
Funder name
Unilever
Alternative name(s)
Funding Body Type
private sector organisation
Funding Body Subtype
For-profit companies (industry)
Location
United Kingdom
Results and Publications
Publication and dissemination plan
The findings from this study will be disseminated amongst the scientific community. We intend to publish our findings in a high-impact peer reviewed scientific journal and present data at appropriate local, national and international conferences by December 2018. In addition, we will produce a lay report of our findings which will be made available to all participants.
IPD sharing statement:
The datasets generated during and/or analysed during the current study are/will be available upon request. Data requests should be submitted to the EHPC coordinator (Catherine.Molloy@lstmed.ac.uk); these are considered by the program leads, and will be subject to data transfer agreements and ethical review if necessary.
Intention to publish date
31/12/2018
Participant level data
Available on request
Basic results (scientific)
See additional file (ISRCTN12909224_BasicResults_4Oct18.pdf)
Publication list
Publication citations
Additional files
- ISRCTN12909224_BasicResults_4Oct18.pdf Uploaded 04/10/2018