Asthma Clinical Trial
Official title:
Nasal Immune Challenge Study
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.
Status | Recruiting |
Enrollment | 24 |
Est. completion date | September 30, 2024 |
Est. primary completion date | September 30, 2024 |
Accepts healthy volunteers | Accepts Healthy Volunteers |
Gender | All |
Age group | 18 Years and older |
Eligibility | Inclusion Criteria: - 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 - Pre-bronchodilator FEV1 =50% predicted - Participants are permitted to have physician-diagnosed mild to moderate asthma which is not poorly controlled as evidenced by an Asthma Control Questionnaire (ACQ-5) score of =1.5. - If they have asthma, they are permitted to be on inhaled corticosteroid (ICS) and a long-acting beta agonist (LABA), but no other controller medication. - Have had no other courses of medication including nasal and systemic corticosteroids, whether prescribed or over-the-counter, in the four weeks before first study dose other than mild analgesia, vitamins and mineral supplements or, for females, oral contraceptives. Exclusion Criteria: - 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 |
Country | Name | City | State |
---|---|---|---|
United Kingdom | Cambridge University Hospitals NHS Foundation Trust | Cambridge | Cambridgeshire |
Lead Sponsor | Collaborator |
---|---|
Cambridge University Hospitals NHS Foundation Trust |
United Kingdom,
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. — View Citation
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Other | Blood CXCL10 response to lipopolysaccharide (LPS) | Difference in CXCL10 after ex-vivo stimulation of blood samples with LPS before and 24 hours after nasal challenge with R848 | 24 hours | |
Primary | 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 | Nasal CXCL10 gene expression between healthy and allergic rhinitis participants | Difference in CXCL10 nasal mucosal gene expression at 24 hours after R848 challenge between healthy subjects and those with allergic rhinitis. | 24 hours | |
Secondary | Average body temperature comparison between first and second nasal R848 challenge | Change in participant's temperature between first and second nasal challenge with R848 (as a marker of clinical tolerability). | 2 weeks | |
Secondary | Nasal CXCL10 AUC between first and second nasal challenge | Difference in CXCL10 nasal mucosal protein in nasal mucosal lining fluid over 24 hours expressed as area under curve (AUC) between first and second nasal challenge with R848. | 2 weeks | |
Secondary | Nasal CXCL10 gene expression saline vs R848 single challenge | Difference in nasal CXCL10 gene expression after saline and R848 single challenge | 24 hours | |
Secondary | Nasal CXCL10 gene expression saline vs R848 repeat challenge | Difference in nasal CXCL10 gene expression after saline and R848 repeat challenge | 2 weeks |
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