Exploring Co-infection with Live Attenuated Influenza Vaccine and PneumococcuS in healthy oldEr adults (ECLIPSE)
| ISRCTN | ISRCTN13284643 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN13284643 |
| IRAS number | 343692 |
| Secondary identifying numbers | UK Research and Innovation (UKRI) Grant Code 10077113, CPMS 62446 |
- Submission date
- 23/09/2024
- Registration date
- 15/10/2024
- Last edited
- 14/08/2025
- Recruitment status
- Recruiting
- Overall study status
- Ongoing
- Condition category
- Infections and Infestations
Plain English summary of protocol
Background and study aims
In this study, researchers aim to explore how the body will react to a combination of the flu virus and pneumococcal bacteria, focusing on respiratory infections and nasal immune responses. Pneumococcal bacteria are known to cause chest infections such as pneumonia, more often in young children and older adults. This study aims to investigate co-infection, which could help in developing new treatments and vaccines. An approved nasal vaccine for the flu called the Live Attenuated Influenza Virus (LAIV) will be used to mimic the way the immune system responds to the flu virus. Some participants will also have pneumococcal bacteria introduced into their nose. This co-infection model will have been well tested in younger adults, and the researchers will want to compare these results with a group of older adults. The primary goal of this study will be to understand if this will be safe and easy to study in this age group. Two groups, A and B, will be studied. Participants in the co-infection study (Group A) will be adults between the ages of 60 and 80 years old. They will receive the pneumococcal bacteria on Day 0, and LAIV either on Day –3 (before the pneumococcal bacteria) or Day 3 (after the pneumococcal bacteria). Participants in both groups will either get saltwater or the flu virus, and they will not know which. Group B will receive the LAIV only on Day 0. This group will be open to older (60-80 years old) and younger (18-49 years old) adults. They will not receive the pneumococcal bacteria. Throughout the study, samples will be taken from the nose, throat, saliva, and blood to observe how the immune system responds. Participants will be asked to complete a diary to track symptoms and will collect saliva and nasal samples at home.
Who can participate?
Healthy adults, between 60-80 years old OR 18-49 years old (Group B only).
What does the study involve?
There will be two study groups, A and B. Participants in the co-infection study (Group A) will receive pneumococcal bacteria intranasally (through the nose) on Day 0, and then an approved flu vaccine either on Day –3 (before the pneumococcal bacteria) or Day 3 (after the pneumococcal bacteria). Participants in both groups will either receive saltwater (saline) or the flu virus, and they will not know which one they received. This is called blinding. However, the study staff will not be blinded and will know what each participant has had to ensure participant safety. Throughout the study, samples will be taken from the nose, throat, saliva, and blood to observe how the immune system responds, and a diary will be kept to track immune cells and markers. Participants will collect saliva and nasal samples at home.
What are the possible benefits and risks of participating?
Participants will be a valuable part of a research study that researchers hope will eventually lead to the development of new methods to prevent or treat respiratory infections. However, there will not be a direct benefit to the participant.
When challenging participants with the pneumococcal bacteria, there will be a small risk of infection to them or their close contacts. However, this pneumococcus bacterium has been given in previous studies to healthy adults and older adults with no serious side effects. Around 10% of adults will also carry pneumococcus at any one time without being aware of it. Every participant who tests positive for pneumococcus will take a course of antibiotics at the end of the study, or if they feel unwell, on the advice of a study doctor.
There will also be risks associated with performing study procedures such as fine needle aspirate sampling, throat swabs, and blood/nasal samples. The risks will be limited; however, there will be the potential for procedures to cause some mild discomfort, bruising, or mild pain.
Since several medical tests will be carried out throughout the study, it will be possible to detect previously unknown health issues (e.g., high blood pressure or abnormal blood results). If this does happen, any findings will be discussed with the participant and their GP if ongoing follow-up is required.
Where is the study run from?
Centre for Clinical Vaccinology and Tropical Medicine, Churchill Hospital (UK)
When is the study starting and how long is it expected to run for?
May 2023 to January 2028
Who is funding the study?
Horizon Europe, UKRI
Who is the main contact?
Thejaswini Madupuri, info@ovg.ox.ac.uk
Contact information
Public
Project Manager, Oxford Vaccine Group, Department of Paediatrics, University of Oxford, CCVTM, Churchill Hospital
Oxford
OX3 7LE
United Kingdom
| Phone | +44 (0)1865 611400 |
|---|---|
| thejaswini.madupuri@paediatrics.ox.ac.uk |
Scientific, Principal Investigator
Oxford Vaccine Group, Centre for Clinical Vaccinology and Tropical Medicine (CCVTM), Churchill Hospital Old Road, Headington
Oxford
OX3 7LE
United Kingdom
 ORCID ID |
0000-0001-9513-5183 |
|---|---|
| Phone | +44 (0)1865 611400 |
| katrina.pollock@paediatrics.ox.ac.uk |
Study information
| Study design | Randomized controlled trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Home, Hospital, Internet/virtual, Medical and other records |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details below to request a patient information sheet |
| Scientific title | Human co-Infection challenge study of S. pneumoniae (Spn) and Live Attenuated Influenza Vaccine (LAIV) in older healthy adults |
| Study acronym | ECLIPSE |
| Study objectives | Primary Objective: To determine if a co-infection human challenge model with LAIV and S. pneumoniae (Spn6B) is feasible and safe. Secondary Objectives: 1. If co-infection with LAIV and Spn6B alters upper and lower respiratory tract infection symptoms 2. How primary LAIV vaccination alters the: 2.1. Risk of secondary Spn6B carriage 2.2. The density of secondary Spn6B carriage 2.3. Duration of secondary Spn6B carriage 3. How primary Spn6B challenge or carriage alters the: (a) Risk of secondary LAIV infection (ie. detection of LAIV) 3.1. Viral load of secondary LAIV infection (density over time) 4. If nasal colonisation with other respiratory viruses and bacteria is detectable 5. To evaluate changes in nasal cell phenotype and function over time |
| Ethics approval(s) |
Approved 30/10/2024, East Midlands – Leicester South Research Ethics Committee (2 Redman Place, Stratford, London, E20 1JQ, United Kingdom; +44 (0)2071048193; Leicestersouth.rec@hra.nhs.uk), ref: 24/EM/0200 |
| Health condition(s) or problem(s) studied | Human co-infection challenge study of S. pneumoniae (Spn) and live attenuated influenza vaccine |
| Intervention | Design This will be a single-blind randomised controlled human co-infection study using a previously established pneumococcal and LAIV infection model. Eligible healthy, older adults will receive an intranasal challenge with LAIV/saline on Day -3 followed by a challenge with Spn6B on Day 0. Participants will receive a further intranasal challenge on Day 3 with the LAIV/saline option they did not receive on Day -3 (participants who received saline on Day 3 will receive a LAIV on Day 3, and those who received LAIV will receive saline). All study participants will be blinded to the order of challenge agents (LAIV first or saline first). In parallel, a control group of younger and older adults will be vaccinated with intranasal LAIV only, for comparison. Data from the control group will allow the determination of the impact of immune responses to LAIV in the absence of pneumococcal co-infection. Allowing for a 20% expected dropout, the study will enrol up to 60 participants into Group A to complete at least 40 participants. Recruitment may be stopped once the required datasets from 40 participants are available. A participant will be considered enrolled in the study at the point of Baseline Assessment. Recruitment will run over two seasons (autumn/winter 2024 and 2025). Methodology Study visits will occur at the study site. Timings vary between Groups A and B. The Online Screening Questionnaire includes a request to check the GP summary beforehand before inviting to the screening visit. The participant will be invited to a screening visit. There is a different consent form for Groups A and B (reflecting different risks and things to be aware of). Group A also need to fill in an Informed Consent Quiz to show understanding of the study. Inclusion/exclusion criteria will be reviewed, including medical history. The participant will have a physical examination and a set of physical observations performed. The following investigations are performed: blood sampling, ECG, and pregnancy test (if applicable). The screening visit can be combined with a baseline visit if future appointments can be scheduled appropriately within the study timeline. Samples: The study will assess immune responses through samples including blood, nasal wash, nasal cells, throat swabs, nasosorption and saliva samples. They will be taken as per the Schedule of Events. The immune responses in the axillary lymph node tissue will be assessed in a subset of participants across Groups A and B (up to 10 volunteers). Home Sampling: When baseline research samples are taken (Day -7 Group A, Day -3 Group B), the participants will be trained in self-sampling. The home sampling will be conducted at the participant's place of residence. To ensure samples are collected within 15 minutes of the planned time, participants will be asked to fill in the details on redcap and label their samples. Samples will be stored at home in biohazard-appropriate packaging (supplied by the research team) in a freezer. Self-test will include a saliva sample, nasosorption and a symptom diary. |
| Intervention type | Biological/Vaccine |
| Pharmaceutical study type(s) | Not Applicable |
| Phase | Not Applicable |
| Drug / device / biological / vaccine name(s) | Controlled human infection model (CHIM) of live attenuated influenza vaccine (LAIV), Streptococcus pneumoniae (Spn) |
| Primary outcome measure | The absence of SAEs/AESIs relating to inoculation throughout the study will be measured by clinical monitoring at D28 in Group A and D31 in Group B |
| Secondary outcome measures | 1. The absence of SAEs/AESIs relating to inoculation throughout the study will be measured by clinical monitoring at D28 in Group A and D31 in Group B 2. Colonisation risk, density, and duration quantification of secondary Spn6B carriage will be measured by classical culture and molecular methods, including RT-qPCR, 3-5 days after the final visit (Group A: D31-33, Group B: D34-36) 3. Secondary LAIV infection and viral load will be determined by RT-qPCR, 3-5 days after the final visit (Group A: D31-33, Group B: D34-36) 4. Detection of the most common respiratory viruses and other respiratory bacteria will be assessed by microfluidic qPCR, 3-5 days after the final visit (Group A: D31-33, Group B: D34-36) 5. Changes in cell populations, including antigen-specific T and B cells in the nasal mucosa, will be analyzed at different time points, 3-5 days after the final visit (Group A: D31-33, Group B: D34-36) |
| Overall study start date | 01/05/2023 |
| Completion date | 31/01/2028 |
Eligibility
| Participant type(s) | Healthy volunteer |
|---|---|
| Age group | Mixed |
| Lower age limit | 18 Years |
| Upper age limit | 80 Years |
| Sex | Both |
| Target number of participants | Planned Sample Size: 80; UK Sample Size: 80 |
| Key inclusion criteria | 1. Participant is willing and able to give informed consent for participation in the study 2. Healthy adults, ages as specified depending on study group 3. In the Investigator’s opinion, is able and willing to comply with all study requirements 4. Fluent spoken English – to ensure a comprehensive understanding of the research study 5. Willing to allow his or her General Practitioner and consultant, if appropriate, to be notified of participation in the study. 6. Agreement to provide their National Insurance/Passport number for the purposes of TOPS registration and for payment of reimbursement expenses. 7. Females of childbearing potential* with a negative urine pregnancy test at screening and willing to practice adequate contraceptive** measures as per UK Clinical Trial Facilitation Group during the study 8. Participant must live near to study site or in the surrounding area |
| Key exclusion criteria | The participant may not enter the study if ANY of the following apply: 1. Severe and/or uncontrolled cardiovascular disease, respiratory disease, gastrointestinal disease, liver disease, renal disease, endocrine disorder, or neurological illness, as judged by the Investigator (note, mild/moderate well-controlled comorbidities are allowed). Including but not limited to: 1.1. Asplenia or dysfunction of the spleen 1.2. Chronic respiratory disease (e.g. asthma [requiring medication (including salbutamol inhaler) within last 12 months], COPD, bronchiectasis and sleep apnoea) 1.3. Chronic heart disease (e.g. angina, ischaemic heart disease, chronic heart failure) – controlled and stable hypertension may be included 1.4. Severe chronic kidney disease (e.g. nephrotic syndrome, kidney transplant, requires dialysis) 1.5. Chronic liver disease (e.g. cirrhosis, biliary atresia, hepatitis) 1.6. Chronic neurological disease that limits mobility, bulbar or respiratory function (including stroke, Parkinson’s disease, dementia and multiple sclerosis) 1.7. Diabetes mellitus (including diet-controlled) 2. Receipt of immunosuppressive therapy such as anti-cancer chemotherapy or radiation therapy within the preceding 12 months or long-term systemic corticosteroid, Roaccutane, or disease modifying anti-rheumatoid drugs therapy (for more than 7 consecutive days within the 3 months prior to enrolment) 3. Individuals with cochlear ear implants 4. Individuals with major cerebrospinal fluid leaks (e.g. following traumatic, major skull surgery, or requiring CSF shunts) 5. Subjects with known or suspected immune deficiency (e.g. known IgA deficiency, immotile cilia syndrome, or Kartagener’s syndrome) 6. History of frequent nose bleeds 7. Bleeding disorders 8. No major pneumococcal illness requiring hospitalisation in the last 10 years 9. Maternal (Group B) 10. Female participants who are pregnant 11. Female participants who are lactating 12. Female participants who intend to become pregnant during the study 13. Female participants unable to take contraception measures during the study (from consent to final study visit) 14. Close contact with individuals at increased risk of pneumococcal disease (eg. children under 5 years, immunocompromised individuals 15. Healthcare workers 16. On medication that may affect the immune system in any way eg. steroids 17. Taking long term antibiotics, nasal/inhaled steroids, oral antiplatelets or warfarin therapy 18. Allergy to penicillin, amoxicillin, gentamicin, gelatin, lidocaine or any ingredient of the influenza vaccine 19. Current regular smoker/vaper (smokes daily) or previous regular smoker/vaper than has stopped smoking/vaping less than 12 months ago (up to 10 pack-years smoking history allowed) 20. History of drug or alcohol abuse (frequently drinking over the recommended alcohol intake limit: men and women should not regularly drink more than 14 units per week) 21. Any clinically significant finding on screening investigation bloods 22. Not able to make specific inoculation/vaccination visit dates required for the study, or overseas travel booked for 21 days following baseline testing 23. Received any influenza vaccine in the same winter season as they are recruited 24. Pneumococcal vaccination (which we can confirm is not the PCV vaccine) in the last 1 year (older adults who have had pneumococcal vaccination but not influenza may be considered for Group B – LAIV only) 25. Participants who have received the Pneumococcal Conjugate Vaccine specifically within the last 3 years (this would not be given routinely in the UK schedule) 26. Previous involvement in a clinical trial with Pneumococcal inoculation in the last 3 years 27. Scheduled elective surgery or other procedures requiring general anaesthesia during the study 28. Participants who have participated in another research trial involving an investigational product in the past 12 weeks 29. Any other issue which, in the opinion of the study staff, may: 29.1. Put the participant or their contacts at risk because of participation in the study 29.2. Adversely affect the interpretation of the study results, or 29.3. Impair the participant’s ability to participate in the study |
| Date of first enrolment | 08/11/2024 |
| Date of final enrolment | 01/02/2026 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centre
Oxford
OX3 7LE
United Kingdom
Sponsor information
Hospital/treatment centre
Research Governance, Ethics & Assurance Team (RGEA), Boundary Brook House, Churchill Drive, Headington
Oxford
OX3 7GB
England
United Kingdom
| RGEA.sponsor@admin.ox.ac.uk | |
| Website | https://www.ox.ac.uk/ |
"ROR" |
https://ror.org/052gg0110 |
Funders
Funder type
Government
Government organisation / National government
- Alternative name(s)
- UKRI
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 31/12/2028 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not expected to be made available |
| Publication and dissemination plan | Planned publication in a peer-reviewed journal |
| IPD sharing plan | The datasets generated during and/or analysed during the current study are not expected to be made available. Summary data only will be published. No identifiable personal data will be used. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Protocol file | version 1.1 | 02/10/2024 | 20/11/2024 | No | No |
| Protocol file | version 2.1 | 09/04/2025 | 06/06/2025 | No | No |
| Protocol file | version 3.0 | 03/06/2025 | 14/08/2025 | No | No |
Additional files
Editorial Notes
14/08/2025: Uploaded protocol (not peer-reviewed).
06/06/2025: Uploaded protocol (not peer-reviewed). Contact details updated.
20/11/2024: The following changes were made to the trial record:
1. The ethics approval was added.
2. The recruitment start date was changed from 01/11/2024 to 08/11/2024.
3. Uploaded protocol (not peer-reviewed).
23/09/2024: Study's existence confirmed by the National Institute for Health and Care Research (NIHR) (UK).
