Trial record 20 of 21 for:    Open Studies | "Rhinitis, Allergic, Seasonal"

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

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2014 by Imperial College London
Sponsor:
Information provided by (Responsible Party):
Imperial College London
ClinicalTrials.gov Identifier:
NCT02090374
First received: March 11, 2014
Last updated: March 14, 2014
Last verified: March 2014
  Purpose

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.


Condition Intervention
Allergic Rhinitis
Asthma
Latent Tuberculosis
Other: TLR Agonist
Other: Tuberculin nasal challenge
Other: Timothy Grass Pollen

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Factorial Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: Development of Human Nasal Challenge Models With Microbial Constituents and Grass Pollen: Monophosphoryl lipidA, Poly-inosine-cytosine, Poly-inosine-cytosine Stabilised With Poly-L-lysine and Carboxymethylcellulose, Resiquimod, Tuberculin and Timothy Grass Pollen

Resource links provided by NLM:


Further study details as provided by Imperial College London:

Primary Outcome Measures:
  • To document a dose response and time course to nasal challenge in terms of cytokine levels in nasal mucosal lining fluid. [ Time Frame: 3 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change in peak nasal inspiratory flow and nasal symptom scores before and after nasal challenge agent. [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    To develop a set of well tolerated, robust and reproducible (validated) nasal challenge systems with microbial constituents and allergen. To assess tolerability and clinical symptoms, measurements of peak nasal inspiratory flow, total nasal symptom scores as well as clincal examination of nasal mucosa will take place prior to and after administration of nasal challenge agents.

  • To monitor levels of prostaglandin D2 after nasal challenge agent utilising a special probe that touches the surface of the nasal lining and is linked to a mass spectrometer. [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • To document a time course and dose response of nasal curettage mRNA expression in response to nasal challenge agents. [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • Change in nasal mucosal lining appearance on clinical examination before and after administration of nasal challenge agent. [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]
  • Change in blood pressure, pulse, temperature before and after administration of nasal challenge agent. [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 174
Study Start Date: March 2014
Estimated Study Completion Date: February 2017
Estimated Primary Completion Date: August 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: TLR agonist nasal challenge in non-atopic patients Other: TLR Agonist
Preceding incremental ascending dose study to be used to assess top safe dose.
Other Name: 4 TLR agonists to be used including MPLA, Poly IC, Poly IC:LC and Resiquimod
Experimental: TLR agonist nasal challenge in atopic patients Other: TLR Agonist
Preceding incremental ascending dose study to be used to assess top safe dose.
Other Name: 4 TLR agonists to be used including MPLA, Poly IC, Poly IC:LC and Resiquimod
Experimental: Tuberculin nasal challenge in subjects with latent TB Other: Tuberculin nasal challenge
Preceding incremental ascending dose study to be used to assess safe top dose.
Experimental: Tuberculin nasal challenge healthy subjects Other: Tuberculin nasal challenge
Preceding incremental ascending dose study to be used to assess safe top dose.
Experimental: Timothy grass pollen nasal challenge in hay fever subjects Other: Timothy Grass Pollen
Dose: 5000 SQ-U/100µl
Experimental: Timothy grass pollen nasal challenge in asthmatic subjects Other: Timothy Grass Pollen
Dose: 5000 SQ-U/100µl
Experimental: Timothy grass pollen nasal challenge in non-atopic subjects Other: Timothy Grass Pollen
Dose: 5000 SQ-U/100µl

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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 <5 pack years
  • Body mass index in the range18-39

HEALTHY NON-ATOPIC VOLUNTEERS

  • Negative skin prick tests to a range of 6 common aeroallergens: cat, dog, grass pollen, tree pollen, house dust mite, fungal spores
  • Normal blood eosinophil count.

ATOPIC SUBJECTS WITH TIMOTHY GRASS POLLEN SENSITIVITY

  • A clinical history of 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.

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)

SUBJECTS WITH LATENT TUBERCULOSIS

  • Healthy with no lung nor systemic symptoms
  • Positive 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 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 2 months
  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02090374

Contacts
Contact: Trevor Hansel, FRCPath, PhD 0044 20 331 25733 t.hansel@imperial.ac.uk
Contact: Akhilesh Jha, MBBS, MRCP 0044 20 331 25744 a.jha@imperial.ac.uk

Locations
United Kingdom
Imperial Clinical Respiratory Research Unit (ICRRU), St Mary's Hospital Recruiting
Paddington, London, United Kingdom, W2 1NY
Contact: Akhilesh Jha, MBBS, MRCP    0044 20 331 25744    a.jha@imperial.ac.uk   
Contact: Tanushree Tunstall, BSc    0044 20 331 25750    tanushree.tunstall@imperial.ac.uk   
Principal Investigator: Trevor Hansel, FRCPath, PhD         
Sponsors and Collaborators
Imperial College London
Investigators
Principal Investigator: Trevor Hansel, FRCPath, PhD Imperial College London
  More Information

Publications:

Responsible Party: Imperial College London
ClinicalTrials.gov Identifier: NCT02090374     History of Changes
Other Study ID Numbers: 13SM1837, P45058
Study First Received: March 11, 2014
Last Updated: March 14, 2014
Health Authority: United Kingdom: Research Ethics Committee

Keywords provided by Imperial College London:
Hay Fever
Allergy
Asthma
Biomarkers
Chemokines
Cytokines
Eosinophil
Gene Expression
Grass pollen
Human Challenge Study
Inflammation
Innate Immune Response
Lipopolysaccharide
Mucosal Lining Fluid
Nasal
Nasorption
Respiratory
Respiratory Tract Infection
T cells
Tuberculosis
Virus

Additional relevant MeSH terms:
Asthma
Rhinitis
Tuberculosis
Latent Tuberculosis
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Nose Diseases
Respiratory Tract Infections
Otorhinolaryngologic Diseases
Mycobacterium Infections
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Carboxymethylcellulose Sodium
Laxatives
Gastrointestinal Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 20, 2014