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Clinical Trials/NCT02284074
NCT02284074CompletedNot Applicable

Nasal Lipopolysaccharide (LPS) Challenge in Healthy Volunteers (HVs): Investigation of Tolerability, Dose Response and the Expression Profile of Intercellular Adhesion Molecule-1 (ICAM-1)

Imperial College London2 sites in 1 country15 target enrollmentStarted: October 2010Last updated:
Conditions

Trial Snapshot

Phase
Not Applicable
Status
Completed
Enrollment
15
Locations
2
Primary Endpoint
Level of nasal mucosal inter-cellular adhesion molecule-1 (ICAM-1) by gene expression analysis

Study Overview

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.

Detailed Description

STUDY DESIGN AND METHODOLOGY This is a single-centre study which will be carried out at the Imperial Clinical Respiratory Research Unit (ICRRU) at St Mary's Hospital in London Paddington.

RECRUITMENT The study will recruit a total of 15 healthy participants.

STUDY VISITS The study will involve a total of 11 outpatients visits. The screening visit is the initial visit where the study is discussed with the participant and written informed consent is obtained by the PI or his designee. This is done prior to performing any study related procedures. The participant will have had the study information sheet for at least 24 hours prior to the visit.

The visit will include the collection of demographic data, height and weight, physical examination by a doctor, medical history, vital signs, body temperature, 12 lead ECG, laboratory assessments (safety bloods) urine drugs of abuse test and pregnancy tests for females. The participant will also be asked to indicate the presence of any nasal symptoms by completing a modified total nasal symptoms score sheet and perform a peak nasal inspiratory flow (PNIF) test.

If eligible, participants will be asked to return for further study visits. Participants will be given 4 different doses of LPS and a placebo in a randomised manner.

Study Design

Study Type
Interventional
Allocation
Randomized
Intervention Model
Crossover
Primary Purpose
Basic Science
Masking
Double (Participant, Investigator)

Eligibility Criteria

Ages
18 Years to 60 Years (Adult)
Sex
All
Accepts Healthy Volunteers
Yes

Inclusion Criteria

  • Not provided

Exclusion Criteria

  • Not provided

Outcomes

Primary Outcomes

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

Time Frame: 8 hours following nasal lipopolysaccharide (LPS) challenge

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

Secondary Outcomes

  • Nasal mucosal lining fluid IL-6 levels after nasal lipopolysaccharide (LPS) challenge(Up to 8h after nasal LPS challenge)
  • Nasal mucosal lining fluid IL-1beta 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)

Investigators

Sponsor Class
Other
Responsible Party
Sponsor

Study Sites (2)

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