Condition category
Infections and Infestations
Date applied
01/08/2016
Date assigned
25/08/2016
Last edited
11/08/2016
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Background and study aims
Pneumonia is a serious disease which causes swelling (inflammation) in the lungs and is usually caused by a pneumococcus bacterial infection. It is a major cause of death in children under five around the world. There are more than 90 different strains of pneumococcus and currently vaccines only cover around 13. In addition, strain replacement is also occurring, which means that the strains that used to cause disease that we now vaccinate against are being replaced by other strains for which we have no vaccine. There is therefore an urgent need for new vaccines. In most people pneumococcus can occasionally be found harmlessly inhabiting the nose where it does not cause any problem (pneumococcal carriage). About 10% of adults carry pneumococcus at any one time, and almost all adults experience an episode of carriage at least once per year. Carriage acts as a natural vaccine, boosting immunity against pneumococcal infection in adults and children. In order to develop an effective vaccine against pneumonia, it is important to understand how pneumococcal carriage acts to boost immunity. The aim of this study is to inoculate (place in the nose) people with varied doses of pneumococcal bacteria to determine the optimum dose for carriage (dose-ranging study) and then reproduce these findings in sufficient participants to be sure that we have a reproducible method (reproducibility study).

Who can participate?
Healthy adults who speak English fluently.

What does the study involve?
120 healthy participants (who have no current pneumococcal carriage) receive a small dose of live pneumococcal bacteria into each nostril, at a range of different concentrations. Six groups of participants are inoculated with a strain called serotype 23F and 60 with a strain called serotype 6B. After 48 hours and one week and 4 weeks, participants have samples taken from their nose to monitor the presence or absence of pneumococci. At 48 hours and four weeks, participants also have samples of blood and urine taken, as well as having a throat swab and samples taken from the lungs during a bronchoscopy and lavage (where a camera inserted into the lungs via the nose and the a small segment of the right lung is washed before cells are collected) procedure. If a participant becomes a carrier, they are given a three day course of antibiotics at the end of the study to ensure that the pneumococcus has been cleared.
60 additional participants are later recruited and randomly allocated to receive an inoculation of either serotype 23F or 6B, the concentration to use is determined from the first part of the study. After 48 hours and one week and 4 weeks, participants have samples taken from their nose to monitor the presence or absence of pneumococci. At 48 hours and four weeks, participants also have samples of blood and urine taken, as well as having a throat swab and samples taken from the lungs during a bronchoscopy and lavage.

What are the possible benefits and risks of participating?
There are no significant benefits to being involved in the study. Risks are related to blood tests, bronchoscopy (camera into the lungs via the nose) and inoculation (live bacteria put into the nose). Blood tests may cause minor pain or bruising. Inoculation carries a risk of infection including meningitis, pneumonia (chest infection, otitis media (ear infection) or sinusitis. Bronchoscopy carries a risk of chest pain, fever, infection, allergic reaction to sedation or anaesthetic throat spray, coughing up a small amount of blood, sore nose, sore throat, nose bleed, aspiration pneumonia (vomit going into your lungs if not starved of food and fluid before the bronchoscopy), cardiac arrhythmia (unusual heart rhythm and rate), and hoarse voice.

Where is the study run from?
1. Royal Liverpool Hospital (UK)
2. Liverpool School of Tropical Medicine (UK)

When is the study starting and how long is it expected to run for?
April 2011 to January 2013

Who is funding the study?
Bill and Melinda Gates Foundation (USA)

Who is the main contact?
Dr Andrea Collins

Trial website

Contact information

Type

Scientific

Primary contact

Dr Andrea Collins

ORCID ID

Contact details

Liverpool School of Tropical Medicine
Pembroke Place
Liverpool
L3 5QA
United Kingdom

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

11731

Study information

Scientific title

Can Experimental Pneumococcal Carriage in healthy volunteers be established – what dose and strain is best?

Acronym

Study hypothesis

The aim of this study is to determine an optimum inoculum dose of pneumococcal bacteria to develop experimental carriage.

Ethics approval

North West 3 REC - Liverpool East, 11/10/2011, 11/NW/0592

Study design

Non-randomised study

Primary study design

Interventional

Secondary study design

Non randomised 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: Antimicrobial therapy

Intervention

Dose ranging study:
120 healthy adult volunteers are allocated into 10 groups of 10, and are inoculated with 0.1ml pneumococci (well-characterised penicillin sensitive) to each nostril, 60 participants will be inoculated with serotype 23F and 60 with 6B.

Group 1: Participants are inoculated with 0.1ml pneumococci, serotype 23F at a concentration of 1x104 cfu/nostril
Group 2: Participants are inoculated with 0.1ml pneumococci, serotype 23F at a concentration of 2x104 cfu/nostril
Group 3: Participants are inoculated with 0.1ml pneumococci, serotype 23F at a concentration of 4x104 cfu/nostril
Group 4: Participants are inoculated with 0.1ml pneumococci, serotype 23F at a concentration of 8x104 cfu/nostril
Group 5: Participants are inoculated with 0.1ml pneumococci, serotype 23F at a concentration of 1.6x105 cfu/nostril
Group 6: Participants are inoculated with 0.1ml pneumococci, serotype 23F at a concentration of 3.2x105 cfu/nostril
Group 7: Participants are inoculated with 0.1ml pneumococci, serotype 6B at a concentration of 1x104 cfu/nostril
Group 8: Participants are inoculated with 0.1ml pneumococci, serotype 6B at a concentration of 2x104 cfu/nostril
Group 9: Participants are inoculated with 0.1ml pneumococci, serotype 6B at a concentration of 4x104 cfu/nostril
Group 10: Participants are inoculated with 0.1ml pneumococci, serotype 6B at a concentration of 5x104 cfu/nostril
Group 11: Participants are inoculated with 0.1ml pneumococci, serotype 6B at a concentration of 1.6x105 cfu/nostril
Group 12: Participants are inoculated with 0.1ml pneumococci, serotype 6B at a concentration of 3.2x105 cfu/nostril

An additional 20 participants are inoculated with 0.1ml 0.9% saline solution (control)

Saliva, blood, urine, nasal wash, throat swabs are taken at screening. Urine, nasal wash, throat swab are taken at day 2 post inoculation. Nasal wash is taken 7 days after inoculation. Saliva, blood, urine, nasal wash are taken in week 4.
Volunteers will have a total duration of observation and follow up of up to 20 weeks.

Reproducibility study:
60 additional volunteers are recruited and randomly allocated to be inoculated with one of the 2 serotypes (serotype 23F and 6B, 30 in each group). The concentration will be determined by the results of the dose ranging study.

Saliva, blood, urine, nasal wash, throat swabs are taken at screening. Urine, nasal wash, throat swab are taken at day 2 post inoculation. Nasal wash, blood, urine is taken 7 days after inoculation and again at week 4, 5 and 6. At week 7-9 Saliva, blood, urine, nasal wash are taken. Bronchoscopy (and BAL) is optional are performed after week 7-9 after antibiotics have been completed. A final blood sample is taken at week 10-20.
Volunteers will have a total duration of observation and follow up of up to 20 weeks.

Intervention type

Other

Phase

Drug names

Primary outcome measures

Presence of pneumococci is measured using classical culture methods in nasal wash at 48 hours and/or 7 days following inoculation.

Secondary outcome measures

No secondary outcome measures

Overall trial start date

01/04/2011

Overall trial end date

04/01/2013

Reason abandoned

Eligibility

Participant inclusion criteria

1. Adults aged 18-60 years old
2. Fluent English spoken

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

Planned Sample Size: 200; UK Sample Size: 200

Participant exclusion criteria

1. Close contact with young children, elderly or immunocompromised individuals (either at work or home)
2. Asthma or pre-existing lung disease
3. Cigarette smoking of greater than 20 pack years
4. Chronic illness
5. Pregnancy
6. Penicillin allergy

Recruitment start date

21/10/2011

Recruitment end date

08/12/2012

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Royal Liverpool Hospital
Prescot Street
Liverpool
L7 8XP
United Kingdom

Trial participating centre

Liverpool School of Tropical Medicine
Pembroke Place
Liverpool
L3 5QA
United Kingdom

Sponsor information

Organisation

Royal Liverpool Hospital

Sponsor details

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

Sponsor type

Hospital/treatment centre

Website

Funders

Funder type

Charity

Funder name

Bill and Melinda Gates Foundation

Alternative name(s)

Bill & Melinda Gates Foundation

Funding Body Type

private sector organisation

Funding Body Subtype

foundation

Location

United States of America

Results and Publications

Publication and dissemination plan

Planned publication of a manuscript entitled "Pneumococcal Colonisation is an Asymptomatic Event in Healthy Adults using an Experimental Human Colonisation Model" in PLOS ONE.

Intention to publish date

31/12/2016

Participant level data

Stored in repository

Results - basic reporting

Publication summary

2013 results in http://www.ncbi.nlm.nih.gov/pubmed/23370916
2013 results in http://www.ncbi.nlm.nih.gov/pubmed/23439027
2013 results in http://www.ncbi.nlm.nih.gov/pubmed/23555269
2014 results in http://www.ncbi.nlm.nih.gov/pubmed/25671106
2014 results in http://www.ncbi.nlm.nih.gov/pubmed/24995531
2016 results in http://www.ncbi.nlm.nih.gov/pubmed/27403678

Publication citations

Additional files

Editorial Notes