Development of Human Nasal Challenge Models With Microbial Constituents and Grass Pollen

Summary

The investigators propose the development of a range of nasal spray challenge models to study the way the nose can respond to different types of nasal challenge that elicit different forms of inflammation.

The investigators will carry out nasal challenge with bacterial and viral components and allergens. In this way the nasal upper respiratory tract mucosa is challenged with stimuli of the immune system, causing various types of inflammation. Samples will be taken by blotting the nostril surface and by scraping off tiny surface samples.

The nose will be sprayed with a substance that is a single part of a bacteria or virus, or with an allergen. The material delivered by nasal spray is of high purity and is sterile, containing no live bacteria or viruses. The nasal spray substance contains molecular patterns that are recognised as foreign by the immune system, and at the right dose should stimulate the immune system, causing mild nasal inflammation. The study employs noninvasive methods of sampling using absorptive strips. These strips look and feel like tissue paper, and are applied to each nostril for a period of 1 min. A few pinhead-sized tissue samples are taken from inside the nose, using a small disposable sterile plastic probe that has a tiny scoop on its end. In the nasal lining fluid and tissue samples, measurement will taken of a range of molecules and cells that protect against infections and help the immune response.

By spraying the nose with a challenge agent in this manner, the nasal immune response can be assessed, which can help us better understand how the human immune system cells and molecules respond to bacteria and viruses. In the future, this may allow the testing of new drugs and vaccines, by seeing if they decrease or stop the inflammation after the nasal challenge.

Conditions

• Allergic Rhinitis
• Asthma
• Latent Tuberculosis

Interventions

OTHER

Poly ICLC

Dose escalation: 10ug, 100ug, 500ug Highest dose: 1000ug

OTHER

Poly I:C

Single dose: 500ug

OTHER

R848

High dose: 10ug Low dose: 1-2ug

OTHER

Timothy Grass Pollen

Dose: 5000 SQ-U/100µl

OTHER

Vitamin D

4000U orally

OTHER

Tuberculin

Tuberculin PPD

Sponsors & Collaborators

• Imperial College London

  lead OTHER

Principal Investigators

• Trevor Hansel, FRCPath, PhD · Imperial College London

• Peter JM Openshaw, FRCP, PhD, FRSB, FMedSci · Imperial College London

• Robin Shattock, PhD · Imperial College London

Study Design

Allocation

NON_RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

NONE

Model

FACTORIAL

Eligibility

Min Age

18 Years

Max Age

60 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2014-03-31

Primary Completion

2017-03-31

Completion

2017-03-31

Countries

• United Kingdom

Study Locations