Lung Immune Challenge Study: Controlled Exposure to Inhaled Resiquimod (R848)
NCT Number: NCT06488118
Status: RECRUITING
Study Type: INTERVENTIONAL
Phases: NA
Conditions: Innate Immunity|Mucosal Immunity|Asthma|Viral Infection
Interventions: DRUG: R848|DRUG: Saline
Sponsor: Akhilesh Jha
Collaborators: University of Cambridge
Sex: ALL
Age: ADULT
Enrollment: 36
Study Design: Allocation: RANDOMIZED|Intervention Model: PARALLEL|Masking: SINGLE (PARTICIPANT)|Primary Purpose: BASIC_SCIENCE
Start Date: 2024-05-24
Completion Date: 2025-07
Locations: NIHR Cambridge Clinical Research Facility, Cambridge, Cambridgeshire, CB2 0SL, United Kingdom

Summary:
Respiratory viral infections can be a cause of significant illness, particularly in vulnerable individuals as seen in the COVID-19 pandemic. An underactive or overactive immune response can lead to ineffective resolution of inflammation after an infection, especially in people with airway diseases such as asthma. A better understanding of immune responses to infection that does not rely on cell or animal models is crucial to help develop better treatments for lung inflammation.

An established method of studying inflammation in humans is through careful and controlled exposure (or "challenge") with a mimic of a virus to simulate an infection in a similar manner to that of a virus, but with the advantage of not causing an infection. The investigators have already developed a well-tolerated mimic of human viral infection using a sterile substance called Resiquimod (or R848). Since it does not contain living organisms there is no possibility of being infected. This has been used previously as a nasal spray to cause a mild short-lived inflammation that mimics a mild cold. This has been used safely in a range of people of different ages including those who have asthma.

There are differences however in how the nose and lungs respond to viral infections. This is particularly true in those with airway diseases such as asthma, who have cells in the airways of their lungs that respond in a different way to inflammatory triggers (such as viruses).

The current study aims to build on previous research by developing a new approach of studying inflammation in the lungs using a small volume of Resiquimod. This will be done by gently inhaling a fine mist through a mouthpiece into the lungs. Blood and phlegm samples would then be collected to assess inflammation and how well people tolerate the procedure.

Primary Outcome Measures: Change in Serum or Sputum CXCL10, Change in CXCL10 in serum or induced sputum before and after inhaled R848, 3 weeks from screening visit until 24 hours after inhaled R848 challenge
Secondary Outcome Measures: Change in FEV1, Change in FEV1 after single ascending dose inhaled R848 or saline, Change in FEV1 at 1, 4, 8, 24 and 48 hours after single ascending dose inhaled R848 or saline|Change in Temperature, Change in temperature (degrees celsius) after single ascending dose inhaled R848 or saline, Change in temperature (degrees celsius) at 1, 4, 8, 24 and 48 hours after single ascending dose inhaled R848 or saline|Change in Pulse Rate, Change in Pulse Rate after single ascending dose inhaled R848 or saline, Change in Pulse Rate at 1, 4, 8, 24 and 48 hours after single ascending dose inhaled R848 or saline|Change in Systolic Blood Pressure, Change in systolic blood pressure after single ascending dose inhaled R848 or saline, Change in systolic blood pressure at 1, 4, 8, 24 and 48 hours after single ascending dose inhaled R848 or saline|Change in Peripheral Eosinophil Counts, Change in peripheral eosinophil counts after single ascending dose inhaled R848 or saline, Change in peripheral eosinophil counts at 4, 24 and 48 hours after single ascending dose inhaled R848 or saline|Change in Peripheral Lymphocyte Counts, Change in peripheral lymphocyte counts after single ascending dose inhaled R848 or saline, Change in peripheral lymphocyte counts at 4, 24 and 48 hours after single ascending dose inhaled R848 or saline|Change in Serum CRP, Change in serum CRP after single ascending dose inhaled R848 or saline, Change in serum CRP at 4, 24 and 48 hours after single ascending dose inhaled R848 or saline