Using Multiomics to Define Mechanisms of Rhinovirus-induced Chronic Obstructive Pulmonary Disease Exacerbations to Develop Novel Therapies and Therapeutic Targets

NCT07112235 | Recruiting

• 2 other identifiers: 172255MR/Z504531/1
• Study Type: observational
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this study is to examine exacerbations of chronic obstructive pulmonary disease (COPD) caused by a common cold virus called rhinovirus, to identify new treatments. Exacerbations are flare-ups of respiratory symptoms which are a major cause of ill health in people with COPD, and are most commonly caused by viruses. The main questions the study aims to answer are:

• What processes in the body occur in response to rhinovirus infection, and do the differences between people with COPD and healthy volunteers explain why people with COPD develop more severe illness and exacerbations?
• Can treatments be identified that target these processes to reduce the severity and frequency of exacerbations in people with COPD? The study will compare eligible participants with COPD to healthy volunteers, and will involve intentionally infecting each participant with rhinovirus in a controlled environment. They will undergo baseline investigations prior to infection including a first bronchoscopy. Post-infection each participant will undergo a range of tests, including a second bronchoscopy, to compare how processes in the body, and especially the lungs, differ between people who do and do not have COPD.

Conditions

Exacerbation of COPD; COPD (Chronic Obstructive Pulmonary Disease); Rhinovirus Infection

Keywords

COPD; Chronic Obstructive Pulmonary Disease; Exacerbation; Multiomics; Rhinovirus; Viral challenge study

Outcome Measures

Primary Outcomes (1)

• Lower Respiratory Symptom Score (LRSS)

  Participants will be asked to record their lower respiratory tract symptom scores daily prior to and in the 42 days following viral infection with rhinovirus A-16. Participants will rate their shortness of breath, wheeze, cough, sputum quality and quantity. Total score ranges from 0-17, with higher scores indicating more severe symptoms.

  Participants will record this score daily, from the date of the baseline visit to the final day of their involvement in the study (expected to be day 42).

Secondary Outcomes (9)

• Upper Respiratory Symptom Score (URSS)

  Participants will record this score daily, from the date of the baseline visit to the final day of their involvement in the study (expected to be day 42).

• EXAcerbations of Chronic pulmonary disease Tool-Patient Reported Outcomes (EXACT-PRO)

  Participants will record this score daily, from the date of the baseline visit to the final day of their involvement in the study (expected to be day 42).

• Forced Expiratory Volume in 1 second (FEV1)

  FEV1 will be measured at baseline, on day 0 and every following visit (days 1, 2, 3, 4, 5, 7, 9, 12, 15, 21 and 42).

• Airway Oscillometry

  Investigators will measure participants' airway oscillometry at baseline and clinical visits days 0, 3, 5, 9, 12, 15, 21, 42.

• Fractional exhaled nitric oxide (FeNO)

  Investigators will measure participants' FeNO at baseline and at clinical visits on days 0, 3, 5, 9, 12, 15, 21, 42

Study Arms (3)

COPD Subjects

Participants who meet the diagnostic criteria for COPD

Biological: Rhinovirus-A16

Non-Smoking Controls

Participants who do not meet COPD diagnostic criteria, and who do not have a significant smoking history

Biological: Rhinovirus-A16

Smoking Controls

Participants who do not meet COPD diagnostic criteria, and who do have a significant smoking history

Biological: Rhinovirus-A16

Interventions

Rhinovirus-A16 BIOLOGICAL

Nasal inoculation with a dose equivalent to 100 TCID50 of rhinovirus-A16 inoculum will be administered to all participants in the study

COPD Subjects; Non-Smoking Controls; Smoking Controls

Eligibility Criteria

• Age: 40 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

This study will recruit participants that respond to advertisement or invitations to participate in the study, that meet the eligibility criteria, and whom are willing and able to consent to take part in this study which involves 15 study visits over the course of 7-10 weeks.

You may qualify if:

• Male or female sex
• Age ≥40 years and ≤75 years at the time of signing the consent form
• Medical history or clinical diagnosis of COPD
• Significant smoking history, defined as:
• Cumulative smoking history of at least 20 pack years
• Permitted to currently use, or have history of use of, e-cigarettes/vapes
• COPD spirometry criteria:
• Post bronchodilator FEV1 of \<80% and ≥50% predicted for age and height (equivalent to GOLD criteria stage 2 for 'Moderate' severity COPD9)
• Post-bronchodilator FEV1/FVC ratio \<0.7
• β-agonist reversibility: an improvement of less than 12% predicted FEV1 and less than 200mL after 200 micrograms of salbutamol or equivalent short acting beta-2 agonist bronchodilator.
• History of acute exacerbations of COPD as defined by the participant answering "yes" to the question: "do your COPD symptoms get noticeably worse when you catch a cold?"
• Clinically stable with no COPD exacerbations within 8 weeks prior to enrolment
• Permitted to take short and long-acting bronchodilators including beta agonists and muscarinic antagonist inhalers
• Co-morbidity criteria:
• Permitted to have a past medical history of asthma, allergic rhinitis and seasonal rhinitis, but not currently active within 8 weeks prior to enrolment

You may not qualify if:

• Participants with other causes of chronic airflow limitation, including but not limited to:
• Bronchiectasis including cystic fibrosis
• Bronchiolitis obliterans
• Carcinoma of the bronchus
• Fibrosis such as tuberculosis (TB), idiopathic pulmonary fibrosis
• Presence of any significant systemic disease, that in the opinion of the investigator would (a) make participation in the study unduly risky, or (b) significantly interfere with important outcomes being measured.
• For example, cardiovascular, gastrointestinal, hepatic, renal, neurological, musculoskeletal, infectious, endocrine, metabolic, haematological, psychiatric conditions.
• Pregnant, planning to become pregnant, testing positive for pregnancy at the screening visit test, or nursing females during and within 30 days of treatment.
• Treatment with oral, inhaled or nasal corticosteroids within 8 weeks prior to enrolment.
• Treatment with antibiotics in the 8 weeks preceding enrolment.
• Treatment with nasal medications, anti-leukotrienes, anti-histamine at the time of the study.
• Presence (at screening) of serum rhinovirus-A16 neutralising antibodies in a titre \>1:2.
• Individuals with close contact to at risk patient group, including:
• Infants (less than 6 months);
• The extremely elderly or infirm;

Sponsors & Collaborators

• Imperial College London: lead
• Imperial College Healthcare NHS Trust: collaborator

Study Sites (1)

Imperial College Healthcare NHS Trust

London, United Kingdom

RECRUITING

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Sebastian L Johnston

  Imperial College London

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Dominic P Wilkins, MBBS

CONTACT

+44 20 7594 8495; d.wilkins@imperial.ac.uk

Carmen Chan

CONTACT

+447938737992; kai-mun.chan@nhs.net

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 11, 2025
• First Posted: August 8, 2025
• Study Start: October 8, 2025
• Primary Completion (Estimated): March 31, 2027
• Study Completion (Estimated): March 31, 2027
• Last Updated: April 14, 2026

Record last verified: 2026-04

Locations

GB (1)