N/A
N=93
Development of Human Nasal Challenge Models With Microbial Constituents and Grass Pollen
Allergic Rhinitis · Asthma · Latent Tuberculosis
Bottom Line
View on ClinicalTrials.gov: NCT02090374 ↗Enrolled (actual)
93
Serious AEs
0.0%
Results posted
Nov 2021
Primary outcome: Primary: IFN-y Protein Response in Mucosal Lining Fluid — NA; 3.29; 9.42; 8.20 pg/hr/ml
Study Design & Population
- Study type
- Interventional
- Phase
- N/A
- Interventions
- Poly ICLC (Other); Poly I:C (Other); R848 (Other); Timothy Grass Pollen (Other); Vitamin D (Other); Tuberculin (Other)
- Age
- Adult · 18+ yrs
- Sex
- All
- Sponsor
- Imperial College London
- Primary completion
- Mar 2017
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY IFN-y Protein Response in Mucosal Lining Fluid |
NA; 3.29; 9.42; 8.20; 5.10; NA | — |
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.
Eligibility Criteria
INCLUSION CRITERIA
GENERAL FOR ALL SUBJECTS
- Males and females aged 18 to 60 years
- Current non-smokers for last year, maximum of 10 cigs per month, with a smoking history of 3mm larger than a negative saline control.
ASTHMATIC SUBJECTS WITH TIMOTHY GRASS POLLEN SENSITIVITY
- Seasonal grass pollen allergic rhinitis: sneezing, running and itching nose, nasal drip in the UK grass pollen summer season (May-July).
- Specific allergy confirmed by positive intra-epidermal skin prick test to Timothy grass pollen extract (Soluprick, Phleum pratense; ALK, Horsholm, Denmark), a positive reaction being a raised wheal of diameter >3mm larger than a negative saline control.
- Half the asthmatics have clinical history and diagnosis of asthma, requiring therapy with occasional inhaled beta-agonists, but no inhaled corticosteroids for the past 28 days. Half the asthmatics receive regular combined inhaled corticosteroids and long-acting beta-agonists (ICS/LABA)
- For those asthmatics in the resiquimod (TLR 7/8 agonist) arm:
Methacholine PC20 0.35 IU/ml IFN-γ versus control
- Tuberculin skin test (TST), using RT23 tuberculin purified protein derivative (PPD), from Statens Serum Institut (SSI) of Copenhagen. 2 tuberculin units (TU) in 0.1ml injected intradermally (id) : >6mm to <25mm of induration at 48-72h.
- Normal chest X-ray (CXR) or CT scan if performed routinely for clinical reasons
HEALTHY INTERFERON-γ RELEASE ASSAY (IGRA) NEGATIVE VOLUNTEERS
- Age and sex matched to latent TB subjects
- Healthy with no lung nor systemic symptoms
- Negative blood Interferon-γ release assay (IGRA): Quantiferon TB Gold- in-Tube (QFT-it), <0.35 IU/ml IFN-γ versus control
- Tuberculin skin test (TST), using RT23 tuberculin purified protein derivative (PPD), from Statens Serum Institut (SSI) of Copenhagen.
- 2 tuberculin units (TU) in 1ml injected intradermally (id): <6mm of induration at 48-72h.
- Chest X-ray is not required
EXCLUSION CRITERIA
GENERAL
- Recent infections in past 14 days before screening: especially upper respiratory tract illnesses (including colds and influenza), sore throats, sinusitis, infective conjunctivitis.
- Lower respiratory tract infection in past 28 days
- Signs or symptoms of significant nasal anatomical defects, hypertrophy of turbinates, major septum deviation, nasal polyposis injury, ulceration or recurrent sinusitis
- Previous nasal or sinus surgery
- Systemic illnesses that might affect nasal immune responses
- Medical therapy other than that permitted for contraception.
- Treatment with local or systemic corticosteroids during the previous 1 month
- Anti-inflammatory therapy: including non-steroidal anti-inflammatory drugs (NSAIDs)
- tuberculosis at any stage in life
- active infectious disease
- cardiovascular diseases
- respiratory (other than hay fever or asthma where specified)
- hepatic, gastrointestinal, renal, endocrine, infective, haematological, autoimmune, rheumatological, neurological, dermatological,
- neoplastic conditions
- metabolic diseases and extreme obesity
- depression and psychiatric disorders
- Non-smokers: up to 10 cigarettes a year is permitted
- Participation in a therapeutic drug trial in the prior 30 days.
- Inability or unwillingness to use contraception if the patient is a female of child-bearing age.
- Pregnant or breast feeding women
- Inability to provide informed consent
HEALTHY NON-ATOPIC VOLUNTEERS
- Clinical history of allergic rhinitis, allergic asthma or eczema
SUBJECTS WITH LATENT TUBERCULOSIS
- Clinical history of active symptomatic tuberculosis (TB) infection
- Chemoprophylaxis for TB
HEALTHY INTERFERON-γ RELEASE ASSAY (IGRA) NEGATIVE VOLUNTEERS
- Clinical history of TB infection
- Active nasal allergy
- BCG vaccination
Data sourced from ClinicalTrials.gov (NCT02090374). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.