Condition category
Infections and Infestations
Date applied
29/01/2018
Date assigned
12/02/2018
Last edited
12/02/2018
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Background and study aims
Streptococcus pneumoniae, is a type of bacteria that is an important cause of morbidity and mortality in children worldwide. At the same time healthy people often have this bacteria in the upper airway (nasopharynx) without any sign of disease (colonised) which is the main source for transmission to other people. The current pneumococcal conjugate vaccines (PCV) does not protect against all types of this group of bacteria. Novel vaccines aim to provide broader protection against pneumococcus and are currently being developed. To test these new vaccines in future we need to learn more about how the body responds to this bacteria. It has been observed in adults who are colonised for research purposes (experimentally) with this bacteria that a specific immune cell 'monocyte' is present in the airway that correlates with protection against carriage of this bacteria. It is important to understanding whether this immune mechanisms control carriage in children in order to test vaccines. The aim of this study is determine whether nasal monocytes control pneumococcus by assessing the nasal immune responses to pneumococcus in children.

Who can participate?
Children aged 1 to 5 years old who are waiting to undergo a minor procedure requiring general anesthesia.

What does the study involve?
Participants undergo their planned procedure. They have cells from their nose collected, as well as the nasal lining fluid and have a swab taken of the nose to assess bacteria presence. A throat swab is also collected. Blood samples are collected. There is no further follow up.

What are the possible benefits and risks of participating?
There are no direct benefits with participating. This study collects nasal samples in a non-invasive manner. A possible risk for participants related to the nasal scrape is a slight amount of blood due to scratching of the mucosal lining. In over 1000 such samples that we have collected from adult volunteers, we have not had any serious events related to sample collection. We have collected blood cultures in 20 adults that were sampled during five visits to see if this led to transient bacteremia. We did not detect any bacteremia following sample collection. In addition, we are collecting a blood sample, which at the discretion of the anaesthesist, can be collected from the line used for administration of anaesthetics. Samples will be collected by experienced members of the clinical team. Study nurses, as well as researchers at LSTM, are working according to SOPs taking institutional risk assessments into accounts with regards to working with biological samples.

Where is the study run from?
Alder Hey Children’s Hospital (UK)

When is the study starting and how long is it expected to run for?
March 2017 to September 2020

Who is funding the study?
1. Liverpool School of Tropical Medicine (UK)
2. Medical Research Council (UK)

Who is the main contact?
Mr Simon Jochems (Public)

Trial website

Contact information

Type

Public

Primary contact

Mr Simon Jochems

ORCID ID

http://orcid.org/0000-0002-4835-1032

Contact details

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

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

36936

Study information

Scientific title

SNOT: Sampling the Nose Of Toddlers and Young Children

Acronym

SNOT

Study hypothesis

The aim of this study is determine whether nasal monocytes control pneumococcus by assessing the nasal immune responses to pneumococcus in children.

Ethics approval

NHS REC East Liverpool, 16/01/2018, ref: 17/NW/0663

Study design

; Observational; Design type: Cross-sectional

Primary study design

Observational

Secondary study design

Cross sectional study

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

See additional files

Condition

Specialty: Children, Primary sub-specialty: Allergy, Infection and Immunity ; UKCRC code/ Disease: Infection/ Bacterial, viral and other infectious agents

Intervention

Children aged 1-5 years are recruited to this study as UK carriage rates peak at 2 years and start to decline at 5 years. Children without a current infection awaiting a minor procedure that requires general anesthesia at Alder Hey Children’s hospital are recruited. All samples are collected under general anesthesia to reduce potential discomfort and to not have to immobilize the participant during sample collection. All sample collection methods have been previously used in paediatric settings. Nasal cells are collected by gently scraping the inferior turbinate using curettes. Nasal lining fluid is collected using nasosorption devices (synthetic filter paper that adsorbs cytokines). A bacterial nasopharyngeal (NP) swab is collected to assess bacterial presence. An oropharyngeal throat swab is collected to measure viral presence. Up to 3mL of venous blood is collected to measure humoral and cellular immune responses in blood.

Intervention type

Other

Phase

Drug names

Primary outcome measures

The frequency of monocytes in nasal microbiopsies of children carrying pneumococcus and those who don’t is measured by flow cytometry at the study visit.

Secondary outcome measures

1. Pneumococcal carriage is measured using lyta qPCR from nasopharyngeal swabs at study visit
2. Viral infection is measured by multiplex PCR in children that carry pneumococcus or not at study visit
3. Cytokines in nasal lining fluid of children carrying pneumococcus or not is measured using Luminex at study visit
4. Nasal frequency of other immune cells potentially involved in control of carriage, i.e. neutrophils and CD4+ T cells, in children who carry and those who don’t will be compared by flow cytometry at study visit
5. Nasal cells responses to in vitro stimulation with pneumococcus in children who carry pneumococcus or not will be measured by Luminex at study visit
6. Immune cell frequency, phenotype and function will be measured in blood of children who carry pneumococcus or not using flow cytometry at study visit
7. Anntibody levels against pneumococcal capsule and proteins in children who carry pneumococcus or not will be measured using ELISA and multiplex at study visit

Overall trial start date

01/03/2017

Overall trial end date

01/09/2020

Reason abandoned

Eligibility

Participant inclusion criteria

1. Children aged 1-5 years
2. Parent with fluent spoken English - to ensure a comprehensive understanding of the research project and the proposed involvement
3. Capacity of parent to give informed consent
4. Awaiting minor procedure requiring general anesthesia

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

Planned Sample Size: 50; UK Sample Size: 50

Participant exclusion criteria

Exclusion criteria:
1. Taking daily medications that may affect the immune system e.g. systemic steroids or systemic corticosteroids.
2. Having received antibiotics in the preceding 28 days
3. History of respiratory infections requiring hospitalization
4. Involved in another clinical trial unless observational or in follow-up (non-interventional) phase.
5. Disease associated with altered immunity
6. Surgery related to infection
7. Asthma
8. Current severe acute respiratory infection

Recruitment start date

01/03/2018

Recruitment end date

01/09/2019

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Alder Hey Children’s Hospital
E Prescot Road
Liverpool
L14 5AB
United Kingdom

Sponsor information

Organisation

Liverpool School of Tropical Medicine

Sponsor details

Pembroke Place
Liverpool
+44 151 705 3794
United Kingdom

Sponsor type

Hospital/treatment centre

Website

Funders

Funder type

Government

Funder name

Liverpool School of Tropical Medicine

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

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

Planned publication in a high-impact peer reviewed journal.

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

30/09/2020

Participant level data

Other

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes