COPD (Chronic Obstructive Pulmonary Disease)MRVCOPDNCT07112235
Using Multiomics to Define Mechanisms of Rhinovirus-induced Chronic Obstructive Pulmonary Disease Exacerbations to Develop Novel Therapies and Therapeutic Targets
An observational study of COPD (Chronic Obstructive Pulmonary Disease) and Rhinovirus Infection, run by Imperial College London at 1 site in United Kingdom.
Trial 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… Read more about this study
- Who is it for?
- Ages 40 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- COPD (Chronic Obstructive Pulmonary Disease), Rhinovirus Infection, Exacerbation of COPD
- What is being tested?
- Rhinovirus-A16
- How many people
- 50 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 8 Oct 2025to 31 Mar 2027
- Phase
- Observational
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 to 75 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
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.
Who may be able to join
- 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
Show all 33Show fewer
- 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
- Absence of current or previous history of significant respiratory disease, other than COPD, asthma and allergic rhinitis
- Permitted to have a positive skin test for atopy
- Male or female sex
- Age ≥ 40 years and ≤ 75 years at the time of signing the consent form
- No history or clinical diagnosis of COPD
- No significant smoking history, defined as:
- Less than 5 pack year cumulative smoking history
- Has not smoked or used e-cigarettes/vapes in the last 1 year
- Controls spirometry criteria
- FEV1 of ≥80% predicted for age and height
- FEV1/FVC ratio ≥0.7
- Co-morbidity criteria:
- Permitted to have a past medical history of asthma, allergic rhinitis and seasonal rhinitis, but not currently active in the 8 weeks prior to enrolment
- Absence of current or previous history of significant respiratory disease, other than asthma and allergic rhinitis
- Permitted to have a positive skin test for atopy.
- Identical to non-smoking controls, with the exception of smoking history:
- Cumulative smoking history of at least 20 pack years.
- Permitted to currently use, or have history of use of, e-cigarettes/vapes
Who cannot join
- 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.
Show all 19Show fewer
- 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;
- Pregnant and/or breastfeeding women;
- Patients with immunosuppression (e.g., human immunodeficiency virus (HIV), transplant recipients on anti-rejection medications, those undergoing chemo- or immuno-therapy).
- Other factors that in the opinion of the investigator are considered a risk.
- Participation in other clinical research studies 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 in this or other studies, or (c) present an unacceptable visit burden to the participant.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United Kingdom1 site, 1 recruiting
- Recruiting
Imperial College Healthcare NHS Trust
London
Dominic Wilkins, MBBS, +44 20 7594 8495, d.wilkins@imperial.ac.uk
Carmen Chan, kai-mun.chan@nhs.net
About this study
Official title: Using Multiomics to Define Mechanisms of RhinoVirus-induced Chronic Obstructive Pulmonary Disease Exacerbations to Develop Novel Therapies and Therapeutic Targets
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:
Read more
- 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.
Read the detailed description
Study Rationale:
The investigators aim to understand the biological mechanisms that underlie exacerbations of Chronic Obstructive Pulmonary Disease (COPD) to drive the discovery of new treatments.
COPD is the 4th leading cause of death worldwide, causing 3.5 million deaths in 2021. Acute exacerbations of COPD (AECOPD) involve sudden flare-ups of symptoms, commonly triggered by viral infections, and are the major cause of COPD morbidity, mortality and healthcare costs. Developing new treatments for AECOPD requires a better understanding of the processes occurring in the lungs, before and during exacerbations. Naturally-occurring AECOPD are challenging to study in a way that allows reliable measurement of disease mechanisms, and repeated lung sampling can be impractical and potentially dangerous.
The investigators have therefore developed a human rhinovirus challenge experimental model of AECOPD. This involves infecting participants with a common cold virus called rhinovirus (RV). These studies have demonstrated that RV causes mild-to-moderate exacerbations in 95% of COPD subjects, that confounding factors can be controlled to take reliable measurements, and that repeated sampling of the lungs and respiratory tract can safely and easily be performed in a controlled research environment.
The investigators will compare people who have COPD with people who do not have COPD, including smokers and non-smokers, to identify the processes important in COPD. Researchers will measure a range of clinical and scientific outcomes, using cutting-edge 'multiomics' techniques to understand mechanisms in RV-induced AECOPD to an extent that has not been achieved before.
The crucial information that this study generates will be used to identify new treatments to reduce the frequency and severity of AECOPD. Data will be made publicly available for others to use and analyse, and will be integrated with other databases to maximise the scientific benefit that is gained from our participants' contribution to the project.
End of Study:
Follow up period of 42 days
Study Centres:
There will be 1 study centre: Imperial College Healthcare NHS Trust
Study Intervention:
All participants will be inoculated intra-nasally with rhinovirus-A16
Study Sample Size:
25 participants with mild/moderate COPD, 13 smoking controls, 12 non-smoking controls.
Study procedures
- Screening visit: lung function tests (FEV1, FVC and PEF), height and weight/BMI, Medical and surgical history, drug history, pregnancy test for females with childbearing potential, blood sample.
- Baseline visit: Baseline questionnaires, initiation of daily diary card, blood tests (including for haematology, biochemistry and coagulation), vital signs, physical examination, nasosorption, nasal lavage, nasal and oropharyngeal swabs, sputum collection, chest x-ray, electrocardiogram, lung function tests (FEV1, FVC, PEF), FeNO, airway oscillometry and skin prick testing.
- Baseline bronchoscopy: Bronchoscopy including bronchosorption, bronchioalveolar lavage, bronchial brushings and bronchial biopsies.
- Visit Day 0: Viral inoculation visit: Vital signs, physical examination, lung function tests (FEV1, FVC, PEF), airway oscillometry, FeNO, nasosorption, nasal and oropharyngeal swabs, nasal lavage, blood sampling, sputum collection, urine collection and intranasal RV-A16 challenge
- Visit Day 1: Vital signs, physical examination, lung function tests (FEV1, FVC, PEF), nasosorption, nasal and oropharyngeal swabs, nasal lavage, blood sampling, sputum collection, urine collection
- Visit Day 2: Vital signs, physical examination, lung function tests (FEV1, FVC, PEF), nasosorption, nasal and oropharyngeal swabs, nasal lavage, urine collection.
- Visit Day 3: Vital signs, physical examination, lung function tests (FEV1, FVC, PEF), airway oscillometry, FeNO, nasosorption, nasal and oropharyngeal swabs, nasal lavage, blood sampling, sputum collection, urine collection
- Visit Day 4: Vital signs, physical examination, lung function tests (FEV1, FVC, PEF), nasosorption, nasal and oropharyngeal swabs, nasal lavage, urine collection.
- Visit Day 5: Vital signs, physical examination, lung function tests (FEV1, FVC, PEF), airway oscillometry, FeNO, nasosorption, nasal and oropharyngeal swabs, nasal lavage, blood sampling, sputum collection, urine collection
- Visit Day 7 and Bronchoscopy: Vital signs, physical examination, lung function tests (FEV1, FVC, PEF), airway oscillometry, FeNO, nasosorption, nasal and oropharyngeal swabs, nasal lavage, blood sampling, urine collection and bronchoscopy including bronchosorption, bronchioalveolar lavage, bronchial brushings and bronchial biopsies
- Visit Day 9: Vital signs, physical examination, lung function tests (FEV1, FVC, PEF), airway oscillometry, FeNO, nasosorption, nasal and oropharyngeal swabs, nasal lavage, blood sampling, sputum collection, urine collection.
- Visit Day 12: Vital signs, physical examination, lung function tests (FEV1, FVC, PEF), airway oscillometry, FeNO, nasosorption, nasal and oropharyngeal swabs, nasal lavage, blood sampling, sputum collection, urine collection.
- Visit Day 15: Vital signs, physical examination, lung function tests (FEV1, FVC, PEF), airway oscillometry, FeNO, nasosorption, nasal and oropharyngeal swabs, nasal lavage, blood sampling, sputum collection, urine collection.
- Visit Day 21: Vital signs, physical examination, lung function tests (FEV1, FVC, PEF), airway oscillometry, FeNO, nasosorption, nasal and oropharyngeal swabs, nasal lavage, blood sampling, sputum collection.
- Visit Day 42: Vital signs, physical examination, lung function tests (FEV1, FVC, PEF), airway oscillometry, FeNO, nasosorption, nasal and oropharyngeal swabs, nasal lavage, blood sampling, sputum collection. On completion of this visit the participant will have finished the study and will no longer be enrolled.
- Being tested
- Rhinovirus-A16
- Keywords
- COPD, Chronic Obstructive Pulmonary Disease, Exacerbation, Multiomics, Rhinovirus, Viral challenge study
- Medical subject headings
- Pulmonary Disease, Chronic Obstructive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Rhinovirus-A16Biological
Nasal inoculation with a dose equivalent to 100 TCID50 of rhinovirus-A16 inoculum will be administered to all participants in the study
| Study group | Role | What they receive |
|---|---|---|
| COPD Subjects | Participants who meet the diagnostic criteria for COPD Receives: Biological: Rhinovirus-A16 | |
| Non-Smoking Controls | Participants who do not meet COPD diagnostic criteria, and who do not have a significant smoking history Receives: Biological: Rhinovirus-A16 | |
| Smoking Controls | Participants who do not meet COPD diagnostic criteria, and who do have a significant smoking history Receives: Biological: Rhinovirus-A16 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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 be asked to record their upper respiratory tract symptom scores daily prior to and in the 42 days following viral infection with rhinovirus A-16. Participants will rate their symptoms of cough, sneezing, runny nose, blocked nose, headache, sore throat, malaise, and fever. Total score ranges from 0-24, with higher scores indicating more severe symptoms.
Measured: 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 be asked to record scores for symptoms commonly experienced in COPD exacerbations daily prior to and in the 42 days following viral infection with rhinovirus A-16. Participants will rate their chest congestion, cough, mucus quality and quantity, chest discomfort, chest tightness, general breathlessness, shortness of breath whilst performing personal care, indoor activities and outside errands, tiredness, sleep, and anxiety. Total score ranges from 0-100, with higher scores indicating more severe symptoms.
Measured: 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)
Investigators will perform lung function/spirometry at baseline, immediately prior to inoculation, and at every clinical visit after RV inoculation. The primary measure of lung function will be the forced expiratory volume in 1 second (FEV1), which is a measure of larger airway patency and is impaired in COPD and further impaired in exacerbations of COPD.
Measured: 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
Airway oscillometry is a technique used to measure airflow and patency of the airways, and is a more sensitive measure of small airway dysfunction than spirometry and FEV1.
Measured: 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)
FeNO measures the concentration of nitric oxide in exhaled breath from subjects, which is an indicator of airway inflammation.
Measured: Investigators will measure participants' FeNO at baseline and at clinical visits on days 0, 3, 5, 9, 12, 15, 21, 42
Viral load
Investigator will measure the load of rhinovirus-A16 via quantitative PCR in nasal lavage, nasal swabs, sputum and bronchoalveolar lavage (BAL) acquired from participants.
Measured: Nasal lavage and nasal swabs will be performed at baseline and on all post inoculation visits. Sputum will be collected at baseline and on visits on days 0, 1, 3, 5, 9, 12, 15, 21 and 42. BAL will be acquired via bronchoscopy at baseline and day 7.
Cellular interferon response to rhinovirus infection
Investigators will perform laboratory quantification of immune and epithelial cell interferon response to rhinovirus response in vivo.
Measured: Studies performed on cells extracted at baseline (pre-inoculation) bronchoscopy.
Immunological response to rhinovirus infection
Investigators will measure the number of inflammatory cells in bronchial epithelium and in peripheral blood (via flow cytometry of peripheral blood, and single cell RNA sequencing and spatial transcriptomics of bronchial biopsies), and in the expression of alarmins and cytokines on nasal and bronchial epithelium (via proteomic analysis of naso- and broncho-sorption samples).
Measured: Blood will be taken at baseline and at visits on day 0, 1, 3, 5, 7, 9, 12, 15, 21, 42. Nasosorption will be performed at baseline and all visits post inoculation. Bronchial biopsies, bronchosorption will be via bronchoscopy at baseline and day 7.
Evaluation of the respiratory microbiome
Microbial culture and detailed microbiome assessment of sputum samples and bronchoalveolar lavage samples.
Measured: Sputum will be collected at baseline and on visits on days 0, 1, 3, 5, 9, 12, 15, 21 and 42. BAL will be acquired via bronchoscopy at baseline and day 7.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Aug 2025
- Study start8 Oct 2025
- Primary completion31 Mar 2027 (estimated)
- Study completion31 Mar 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for COPD (Chronic Obstructive Pulmonary Disease)Studies of the same condition, open and under way.
- More trials run by Imperial College LondonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Imperial College London
- Sponsor type
- University, hospital or other
- Collaborators
- Imperial College Healthcare NHS Trust
- Responsible party
- Sponsor
- Investigators
- Sebastian L Johnston, Principal investigator, Imperial College London
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07112235
- Sponsor's protocol ID
- 172255
- Other IDs
- MR/Z504531/1
- Acronym
- MRVCOPD
- Status last verified
- Apr 2026
- First submitted
- 11 Jul 2025
- Last updated
- 14 Apr 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: We may share results from this study with anonymised databases, for example the Human Lung Cell Atlas, whereby the valuable data that our participants have generously provided can lead to the maximum scientific gain. However if this does proceed, then the data will be carefully anonymised and reviewed to ensure that it does not contain personally identifiable data, so that our participants retain the strictest confidentiality and privacy.