Nasal Immune Challenge Study

NCT06021002 | Unknown

• 1 other identifier: A095696
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

Respiratory viral infections cause significant illness, especially in vulnerable individuals and is a topic of immense significance during the current COVID-19 global pandemic. Respiratory diseases such as asthma involve inflammation of the airways and viruses are a major cause of asthma attacks. The nose is easier to access than the lungs but has similar cells and is therefore useful to study immune responses throughout the respiratory tract. Rather than study the effects of a live virus on the immune system, it is possible to give a component or mimic of a virus to simulate an infection in a similar but more straightforward manner, without causing disease. In this study we will use a nasal spray containing a sterile substance called Resiquimod (also called R848) to mimic a viral infection. Resiquimod does not contain any living organisms and therefore there is no possibility of developing a real infection. Resiquimod works by binding to receptors in cells that line the inside of the nose (epithelial cells) as well as cells that can fight infection (immune cells). These cells respond to Resiquimod and cause mild inflammation in the nose, similar to a mild cold. We can then take samples to measure this response and investigate how it differs between individuals. This will help us better understand how the human immune system responds to viruses, and which cells and molecules the body uses to defend itself against infection.

Conditions

Innate Inflammatory Response; Asthma; Nasal Allergy

Outcome Measures

Primary Outcomes (1)

• Nasal CXCL10 gene expression baseline vs post-challenge

  Increase in CXCL10 nasal mucosal gene expression at 24 hours after nasal challenge with R848 compared to baseline.

  24 hours

Secondary Outcomes (5)

• Nasal CXCL10 gene expression between healthy and allergic rhinitis participants

  24 hours

• Average body temperature comparison between first and second nasal R848 challenge

  2 weeks

• Nasal CXCL10 AUC between first and second nasal challenge

  2 weeks

• Nasal CXCL10 gene expression saline vs R848 single challenge

  24 hours

• Nasal CXCL10 gene expression saline vs R848 repeat challenge

  2 weeks

Other Outcomes (1)

• Blood CXCL10 response to lipopolysaccharide (LPS)

  24 hours

Study Arms (7)

Single nasal challenge R848 allergic rhinitis

OTHER

Drug: R848

Single nasal challenge R848 healthy

OTHER

Drug: R848

Single nasal challenge saline

OTHER

Single nasal challenge saline allergic rhinitis and healthy

Drug: Saline

Repeat nasal challenge R848 allergic rhinitis

OTHER

Drug: R848

Repeat nasal challenge R848 healthy

OTHER

Drug: R848

Repeat nasal challenge saline

OTHER

Repeat nasal challenge saline allergic rhinitis and healthy

Drug: Saline

Sample collection only

NO INTERVENTION

Sample collection only (no nasal challenge) to optimise laboratory protocols

Interventions

R848 DRUG

Nasal R848 administration

Repeat nasal challenge R848 allergic rhinitis; Repeat nasal challenge R848 healthy; Single nasal challenge R848 allergic rhinitis; Single nasal challenge R848 healthy

Saline DRUG

Nasal saline administration

Repeat nasal challenge saline; Single nasal challenge saline

Eligibility Criteria

• Age: 18 Years+
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participant is willing and able to give informed consent for participation in the study.
• Male or female aged 18 years and above
• Able (in the Investigators opinion) and willing to comply with all study requirements.
• Willing to allow his or her General Practitioner and consultant, if appropriate, to be notified of participation in the study.
• Female participants of child-bearing potential and male participants whose partner is of child-bearing potential must be willing to ensure that they or their partner use effective contraception during the study
• Participant has clinically acceptable laboratory and ECG at enrolment.
• Negative lateral flow or polymerase chain reaction (PCR) test for SARS-CoV-2
• For healthy volunteers:
• No clinical history of allergic rhinitis, asthma or eczema
• Negative skin prick tests or specific IgE response to a panel of common aeroallergens: cat, dog, grass pollen, tree pollen, house dust mite, fungal spores
• Normal blood eosinophil count (\< 300 cells/μL)
• Normal baseline forced expiratory volume (FEV1) i.e. ≥80%
• For volunteers with allergic rhinitis with or without asthma:
• A clinical history of allergic rhinitis symptoms (sneezing, runny or itchy nose) in response to aeroallergens
• At least one positive skin-prick test or specific IgE response to a panel of common aeroallergens: cat, dog, grass pollen, tree pollen, house dust mite, fungal spores

You may not qualify if:

• 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
• Nasal anatomical defects, precluding use of nasal sampling techniques
• The participant may not enter the study if any of the following apply:
• Female participants who are pregnant, lactating or planning pregnancy during the study.
• Respiratory diseases (other than hay fever or asthma where specified)
• Significant medical history of hepatic, cardiovascular, gastrointestinal, renal, endocrine, infective, haematological, autoimmune, metabolic, rheumatological, neurological, dermatological or neoplastic conditions
• Extreme obesity (BMI \>40)
• Depression and psychiatric disorders
• Any other significant disease or disorder which, in the opinion of the Investigator, may either put the participants at risk because of participation in the study, or may influence the result of the study, or the participant's ability to participate in the study.
• Participants who have participated in another research study involving an investigational product in the past 12 weeks
• Smoking in previous 6 months

Sponsors & Collaborators

• Cambridge University Hospitals NHS Foundation Trust: lead

Study Sites (1)

Cambridge University Hospitals NHS Foundation Trust

Cambridge, Cambridgeshire, CB2 0QQ, United Kingdom

RECRUITING

Related Publications (1)

• Jha A, Thwaites RS, Tunstall T, Kon OM, Shattock RJ, Hansel TT, Openshaw PJM. Increased nasal mucosal interferon and CCL13 response to a TLR7/8 agonist in asthma and allergic rhinitis. J Allergy Clin Immunol. 2021 Feb;147(2):694-703.e12. doi: 10.1016/j.jaci.2020.07.012. Epub 2020 Jul 24.

  PMID: 32717253 BACKGROUND

MeSH Terms

Conditions

Inflammation; Asthma

Interventions

resiquimod; Sodium Chloride

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Intervention Hierarchy (Ancestors)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Central Study Contacts

Akhilesh Jha, MBBS, PhD

CONTACT

akhilesh.jha@nhs.net

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Lecturer in Respiratory Medicine

Study Record Dates

• First Submitted: August 21, 2023
• First Posted: September 1, 2023
• Study Start: August 9, 2022
• Primary Completion: September 30, 2024
• Study Completion: September 30, 2024
• Last Updated: September 1, 2023

Record last verified: 2023-08

Locations

GB (1)