NCT02284074

Brief Summary

The purpose of this study is to develop a nasal challenge model that causes a mild degree of inflammation, without causing any pain or symptoms, but that allows us to measure a variety of proteins in nasal secretions which causes inflammation in the nose. The nasal challenge model involves spraying the nostrils in the form of a fine mist with 4 different doses (1, 10, 30 and 100µg per nostril) of lipopolysaccharide (LPS) including a placebo. LPS is a type of protein which has been carefully purified from the outer cell wall of certain bacteria, is sterile and does not contain live bacteria, and will not cause infection. The investigators will measure any inflammation in the nose by looking at cells collected by washing the inside of the nose (nasal lavage) and placing small strips of paper in the nasal cavity. The paper absorbs the nasal fluid and the chemicals produced during inflammation and can be extracted from the paper and analysed in the laboratory. The investigators will also be collecting a small amount of nasal epithelium taken by way of a nasal scrape; this is done by using a Rhinoprobe, a small plastic curette which is used to scrape a small piece of lining of the nose. The investigators hope that information obtained from this study will be used in future studies that will test new study drugs designed to treat diseases of the airways and lungs ( like asthma and chronic obstructive pulmonary disease (COPD) and hay fever.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
15

participants targeted

Target at below P25 for not_applicable healthy

Timeline
Completed

Started Oct 2010

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

October 1, 2010

Completed
6 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 1, 2011

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

April 1, 2011

Completed
3.5 years until next milestone

First Submitted

Initial submission to the registry

September 19, 2014

Completed
2 months until next milestone

First Posted

Study publicly available on registry

November 5, 2014

Completed
Last Updated

September 15, 2023

Status Verified

September 1, 2023

Enrollment Period

6 months

First QC Date

September 19, 2014

Last Update Submit

September 13, 2023

Conditions

Healthy

Keywords

Lipopolysaccharide (LPS)BiomarkersChemokinesCytokinesGene ExpressionNasal ChallengeInflammationNasalNasosorptionRespiratory

Outcome Measures

Primary Outcomes (1)

  • Level of nasal mucosal inter-cellular adhesion molecule-1 (ICAM-1) by gene expression analysis

    Measurement of gene expression (mRNA) for inter-cellular adhesion molecule-1 (ICAM-1) in nasal mucosal curettage samples, 8h following nasal lipopolysaccharide (LPS) challenge.

    8 hours following nasal lipopolysaccharide (LPS) challenge

Secondary Outcomes (3)

  • Nasal mucosal lining fluid IL-1beta levels after nasal lipopolysaccharide (LPS) challenge

    Up to 8h after nasal LPS challenge

  • Nasal mucosal lining fluid IL-6 levels after nasal lipopolysaccharide (LPS) challenge

    Up to 8h after nasal LPS challenge

  • Nasal mucosal lining fluid CXCL8 levels after nasal lipopolysaccharide (LPS)

    Up to 8h after nasal LPS challenge

Study Arms (5)

Nasal LPS spray - placebo

EXPERIMENTAL

This is a 5-way crossover, randomised, placebo-controlled study. Arms consists of the following nasal challenges: placebo, 1, 10, 30 and 100µg LPS.

Other: Nasal LPS spray

Nasal LPS spray 1µg

EXPERIMENTAL

This is a 5-way crossover, randomised, placebo-controlled study. Arms consists of the following nasal challenges: placebo, 1, 10, 30 and 100µg LPS.

Other: Experimental: Nasal LPS spray 1µg

Nasal LPS spray 10 µg

EXPERIMENTAL

This is a 5-way crossover, randomised, placebo-controlled study. Arms consists of the following nasal challenges: placebo, 1, 10, 30 and 100µg LPS.

Other: Experimental: Nasal LPS spray 10 µg

Nasal LPS spray 30 µg

EXPERIMENTAL

This is a 5-way crossover, randomised, placebo-controlled study. Arms consists of the following nasal challenges: placebo, 1, 10, 30 and 100µg LPS.

Other: Experimental: Nasal LPS spray 30 µg

Nasal LPS spray 100 µg

EXPERIMENTAL

This is a 5-way crossover, randomised, placebo-controlled study. Arms consists of the following nasal challenges: placebo, 1, 10, 30 and 100µg LPS.

Other: Experimental: Nasal LPS spray 100 µg

Interventions

Nasal LPS sprayOTHER

LPS solution (250µl) will be prepared at 10, 100, 300 and 1000µg/ml, 100µl is administered to each nostril, both nostrils will be sprayed. The dose per nostril corresponds to 1, 10, 30 and 100µg.

Nasal LPS spray - placebo
Experimental: Nasal LPS spray 1µgOTHER

LPS solution (250µl) will be prepared at 10, 100, 300 and 1000µg/ml, 100µl is administered to each nostril, both nostrils will be sprayed.

Nasal LPS spray 1µg
Experimental: Nasal LPS spray 10 µgOTHER

LPS solution (250µl) will be prepared at 10, 100, 300 and 1000µg/ml, 100µl is administered to each nostril, both nostrils will be sprayed.

Nasal LPS spray 10 µg
Experimental: Nasal LPS spray 30 µgOTHER

LPS solution (250µl) will be prepared at 10, 100, 300 and 1000µg/ml, 100µl is administered to each nostril, both nostrils will be sprayed.

Nasal LPS spray 30 µg
Experimental: Nasal LPS spray 100 µgOTHER

LPS solution (250µl) will be prepared at 10, 100, 300 and 1000µg/ml, 100µl is administered to each nostril, both nostrils will be sprayed.

Nasal LPS spray 100 µg

Eligibility Criteria

Age18 Years - 60 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64)

You may qualify if:

  • Males and females aged 18 to 60 years
  • Current non-smokers for last 6 months (\<5 cigs per week), with a smoking history of \<5 pack years
  • BMI 20-30 kg/m2

You may not qualify if:

  • History of allergy
  • Upper airway infection in 2 weeks before screening
  • Lower respiratory tract infection in past 3 months
  • Treatment with local or systemic corticosteroids during previous 2 months
  • Signs or symptoms of chronic rhinitis, hypertrophy of turbinates, major septum deviation, nasal polyposis or recurrent sinusitis
  • Previous nasal or sinus surgery
  • Clinically significant cardiovascular, hepatic, GIT, renal, endocrine, infective, haematological, neurological, dermatological, neoplastic conditions, gastro-oesophageal reflux, depression, TB
  • Participation in a therapeutic drug trial in the prior 30 days.
  • Medical therapy other than that permitted for contraception.
  • Positive pregnancy test
  • Inability or unwillingness to use contraception if the patient is a female of child-bearing age.
  • History of drug abuse or urine test showing evidence of recreational drug abuse

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Imperial Clinical Respiratory Research Unit (ICRRU), St Mary's Hospital

Paddington, London, W2 1NY, United Kingdom

Location

Related Publications (32)

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  • Dhariwal J, Kitson J, Jones RE, Nicholson G, Tunstall T, Walton RP, Francombe G, Gilbert J, Tan AJ, Murdoch R, Kon OM, Openshaw PJ, Hansel TT. Nasal Lipopolysaccharide Challenge and Cytokine Measurement Reflects Innate Mucosal Immune Responsiveness. PLoS One. 2015 Sep 14;10(9):e0135363. doi: 10.1371/journal.pone.0135363. eCollection 2015.

    PMID: 26367003DERIVED

MeSH Terms

Conditions

Inflammation

Condition Hierarchy (Ancestors)

Pathologic ProcessesPathological Conditions, Signs and Symptoms

Study Officials

  • Trevor T Hansel, FRCPath, PhD

    Imperial College London

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, INVESTIGATOR
Purpose
BASIC SCIENCE
Intervention Model
CROSSOVER
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

September 19, 2014

First Posted

November 5, 2014

Study Start

October 1, 2010

Primary Completion

April 1, 2011

Study Completion

April 1, 2011

Last Updated

September 15, 2023

Record last verified: 2023-09

Locations

GB(1)