Condition category
Infections and Infestations
Date applied
15/03/2018
Date assigned
14/05/2018
Last edited
08/05/2018
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Background and study aims
Pneumococcal bacteria can cause pneumonia, meningitis, sepsis and otitis media. These diseases combined are the largest killers of children under 5 years old globally. Better vaccines are needed to help prevent these diseases. Pneumococcal bacteria are carried in the nose of one in ten of the healthy adult population and in higher amounts of children, up to nine in ten, this is referred to as colonisation.
We have developed a model to investigate the human immune response to pneumococcal bacteria present in the nose. This model involves putting the bacteria (inoculation) into the nose of healthy volunteers and monitoring if the bacteria remain in the nose through follow up visits by performing nasal washes. This model has been successfully used for 6 years in Liverpool and we can now achieve a reproducible rate of colonisation (40-50% post inoculation). We would like to obtain cellular samples from the nose by taking small scrapes from inside the nose. We do not know if taking these samples will provide enough cells to carry out analysis, reduce the rate of experimental colonisation and if they will result in any bacteria in the blood stream. We aim to investigate if adequate tissue can be sampled from the nose of healthy volunteers using a small probe. The samples will be analysed in the laboratory to determine if the cell numbers and types are enough to perform immune system tests on.We also aim to determine if the repeated sampling of the nose will affect the number of volunteers that become colonised with the bacteria following inoculation. We also want to investigate if the sampling method will cause any bacteria to move into the blood stream, this will be achieved by taking a blood sample before and 15 minutes after each nasal sample.

Who can participate?
Adults aged 18-50

What does the study involve?
Healthy volunteers will have small amounts of live bacteria put in their noses. They will be followed up in clinic for 2 weeks when samples will be taken to see if the bacteria are still present in their nose. We expect that 40-50% of volunteers will "carry" the bacteria from previous studies therefore we want to see if this rate of carriage remains the same in this study whilst we are taking repeated samples from their nose.

What are the potential risks and benefits of participating?
There are no direct benefits to the participants however they will be part of vaccine development for future generations. Healthy volunteers will be compensated for their time and inconvenience.

Where is the study run from?
Royal Liverpool University Hospital (UK)

How long is the trial expected to run for?
June 2015 to November 2015

Who is funding the study?
UK Medical Research Council

Who is the main contact?
Dr Andrea Collins
andrea.collins@lstmed.ac.uk

Trial website

www.lstmed.ac.uk/pneumoniavaccine

Contact information

Type

Scientific

Primary contact

Dr Andrea Collins

ORCID ID

Contact details

3rd Floor
Accelerator Building
Liverpool School of Tropical Medicine
1 Daulby Street
Liverpool
L7 8XZ
United Kingdom
0151 702 9486
andrea.collins@lstmed.ac.uk

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

15/NW/0146

Study information

Scientific title

Pilot study of repeated mucosal sampling on experimental human pneumococcal colonisation (EHPC) model

Acronym

Study hypothesis

The principle objective is to evaluate if repeated mucosal sampling will obtain sufficient tissue for immunological assessment.

Ethics approval

Research Ethics Committee North West: Liverpool East, 05/05/2015, ref: 15/NW/0146

Study design

Healthy volunteers will be nasally inoculated with Pneumococcal bacteria. Repeated mucosal samples will be taken during follow up visits to determine if adequate tissue can be obtained for immunological assessment. We will determine if repeated mucosal samples affect the rates of colonisation following inoculation.

Primary study design

Observational

Secondary study design

Cohort study

Trial setting

Hospitals

Trial type

Other

Patient information sheet

Condition

Nasal colonisation with pneumococcal bacteria

Intervention

All volunteers will have screening samples taken including nasal wash, nasal cell samples, nasosorption and blood samples. A clinical examination will be performed during the screen visit and a pregnancy test for females will be completed. Volunteers that pass screening will attend the clinic a few days later for the inoculation. This will involve putting a small amount of liquid containing pneumococcal bacteria inside each nostril. Full safety instructions including a course of antibiotics and 24 hour access to medical assistance will be provided.
Volunteers are followed up in clinic at day 2, 7, 9 and 14 post inoculation to review their symptoms and collect samples. Volunteers are invited to undergo a bronchoscopy at the end of the study, they do not have to take part in the bronchosocopy part of the study to participate in the study.



Intervention type

Other

Phase

Drug names

Primary outcome measures

The principle objective is to evaluate if repeated mucosal sampling will obtain sufficient tissue for immunological assessment. Nasal cell yield will be measured using the flow cytometer to count the cell populations from the nasal cell samples taken at baseline, day 2, 7, 9 and 14 post-inoculation.

Secondary outcome measures

1. To evaluate the effect of repeated sampling of the nasal mucosa (lining of the nose) on the acquisition of pneumococcal colonisation. Pneumococcal colonisation is measured using microbiological techniques. The nasal wash pellet is plated onto agar plates and incubated for 48 hours using our previous published methods. Our previous studies have shown experimental colonisation rates of 40-60% following inoculation. The results of this study will be compared to previous healthy volunteer studies involving inoculation with 6B pneumococcus.
2. To evaluate if repeated mucosal sampling affects colonisation density and duration compared to previous EHPC studies. Pneumococcal colonies are counted from diluted nasal wash by plating the pellet using a Miles and Mizra technique. This is performed at baseline and day 2, 7, 9 and 14 post inoculation. The duration of colonisation is classed as the final timepoint at which pneumococcal bacteria is identified using classical microbiolgical techniques. The density and duration from this study will be compared to results from previous EHPC studies following inoculation of healthy volunteers to determine if the repeated nasal sampling technique has reduced the acquisition rates.
3. To evaluate participant comfort level following repeated mucosal sampling. Participants were asked to complete a Likert-type questionnaire to rate the level of comfort experienced with each mucosal sampling technique.
4. To evaluate the kinetics of nasal inflammatory response during pneumococcal colonisation. Cytokine levels are measured from the nasosorption sample using the Luminex machine. The levels measured on day 2, 7, 9 and 14 will be compared with the levels measured at baseline.
5. To evaluate if nasal sampling of cells causes a transient bacteraemia – patient safety issue. Paired blood cultures will be taken during each visit where nasal cell samples are taken. The first blood culture will be taken prior to nasal sampling and the 2nd blood culture will be taken 15 minutes post nasal cell sampling. These paired blood cultures will be taken at baseline, day 2, 7, 9 and 14 post inoculation. Aerobic and anaerobic blood cultures will be incubated for 48 hours and reported as per hospital guidelines. Presence of any bacteria in the blood culture post sampling will be classed as a possible transient bacteraemia.
6. To evaluate if pneumococcal killing by alveolar macrophages is increased following nasal colonisation. Bronchial alveolar lavage samples will be used to isolate alveolar macrophages. These cells will be incubated with pneumococcal bacteria overnight. The pneumococcal killing will be measured by counting the recovered pneumococcal bacteria following incubation with the macrophages compared to bacteria that were not incubated with macrophages. This demonstrates the number of bacteria killed by the alveolar macrophages. Healthy volunteers that have been colonised with SPN following inoculation will be compared with negative controls.

Overall trial start date

17/06/2015

Overall trial end date

24/11/2015

Reason abandoned

Eligibility

Participant inclusion criteria

1. Has capacity to give informed consent
2. Aged 18-50 years (ages chosen to minimise the risk of pneumococcal infection)
3. Speaks fluent English

Participant type

Healthy volunteer

Age group

Adult

Gender

Both

Target number of participants

20

Participant exclusion criteria

1. Currently involved in another study unless observational or in follow-up phase (non-interventional)
2. Are in close contact with at risk individuals (children under 5 years, immunosuppressed adults, elderly, chronic ill health) – to minimise risk of pneumococcal transmission
3. Current regular smoker (smokes daily) - to minimise risk of pneumococcal disease
4. Significant smoking history [defined as someone who has previously smoked more than 20 cigarettes per day for 10 years or the equivalent (>10 pack-years)] – to minimise risk of pneumococcal disease
5. Asthma (on regular medication) or respiratory disease – to minimise risk of pneumococcal disease
6. Pregnant - to minimise the risk of pneumococcal disease
7. On medication that may affect the immune system in any way e.g. steroids, steroid nasal spray
8. On medication that affects inflammation e.g. aspirin
9. On medication that affects clotting of blood e.g. dipyridamole or warfarin
10. Been involved in a clinical trial involving EHPC and bacterial inoculation over the last 3 years
11. Unable to give fully informed consent
12. Current acute severe febrile illness - to avoid inoculation in participants that may have current infection.

Recruitment start date

27/06/2015

Recruitment end date

01/11/2015

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Royal Liverpool University Hospital
Prescot Street Liverpool L7 8XP
Liverpool
L7 8XP
United Kingdom

Sponsor information

Organisation

Royal Liverpool and Broadgreen University Hospital Trust

Sponsor details

Research and Development Department
4th Floor Linda McCartney Centre
Prescot Street
Liverpool
L7 8XP
United Kingdom

Sponsor type

Hospital/treatment centre

Website

Funders

Funder type

Not defined

Funder name

Medical Research Council

Alternative name(s)

MRC

Funding Body Type

government organisation

Funding Body Subtype

Federal/National Government

Location

United Kingdom

Results and Publications

Publication and dissemination plan

Results will be published in peer reviewed scientific journals.

Intention to publish date

01/12/2018

Participant level data

Not provided at time of registration

Results - basic reporting

We found that the mucosal sampling yielded enough tissue to perform the immunological tests required.
The study found that the repeated sampling method did not alter colonisation rates when compared to previous studies.
The study found that the repeated mucosal sampling methods did not cause any transient bacteraemia.

Publication summary

Publication citations

Additional files

Editorial Notes