A pneumococcal human challenge study in adults aged 50-84 years

Not Applicable

• Conditions: Pneumoccocal carriage; Infections and Infestations

• Registration Number: ISRCTN71362981
• Lead Sponsor: iverpool School of Tropical Medicine

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2024-04-12
• Last Update Posted: 9 September 2024
• Study Completion: 2025-10-30

Recruitment & Eligibility

• Status: Ongoing
• Sex: All
• Target Recruitment: 15

Inclusion Criteria

1. Healthy adults aged 50-84 (inclusive, at the time of consent and inoculation) years old
2. World Health Organisation performance status 0 (able to carry out all normal activity without restriction) or 1 (restricted in strenuous activity but ambulatory and able to carry out light work)
3. Access to telephone and e-mail
4. Fluent spoken English – to ensure a comprehensive understanding of the research project
5. Capacity to provide written informed consent in English

Exclusion Criteria

Individuals may not participate in the study if they are/have:

Research participant:
1. Currently involved in another study unless observational or non-interventional, excluding the EHPC bronchoscopy study (at the discretion of the study team) and exceptions may be applied at the discretion of the CI/PI to ensure no harm comes to the participants (e.g. excessive blood or nasal sampling)
2. Participated in a previous Spn6B EHPC study within 3 years

Nasal carriage:
Participants who have natural pneumococcal identified at screening

Vaccination:
1. Had any vaccination within 28 days of enrolment (defined as the time of inoculation) other than against influenza or COVID-19 which is permissible up to 14 days before inoculation
2. Had a pneumococcal conjugate vaccine*

Allergy:
Allergy to beta-lactam antibiotics (including penicillin and amoxicillin)

Medical history leading to increased risk of severe infection, illness including but not limited to:
1. Asplenia or dysfunction of the spleen
2. Chronic respiratory disease (e.g. asthma [requiring medication (including salbutamol inhaler) within last 12 months], COPD, bronchiectasis and sleep apnoea)
3. Chronic heart disease (e.g. angina, ischaemic heart disease, chronic heart failure) - controlled and stable hypertension may be included
4. Chronic kidney disease (e.g. kidney transplant, regular dialysis, CKD3-5)
5. Chronic liver disease (e.g. cirrhosis, hepatitis)
6. Chronic neurological disease that limits mobility, bulbar or respiratory function (including stroke, Parkinson’s disease, dementia and multiple sclerosis)
7. Diabetes mellitus (including diet controlled)
8. Cancer within the past 5 years (except for basal cell carcinoma of the skin, melanoma in situ and cervical carcinoma in situ)
9. Receipt of immunosuppressive therapy such as anti-cancer immunotherapy, chemotherapy or radiation therapy within the preceding 5 years or long-term systemic corticosteroid, Roaccutane, or disease-modifying anti-rheumatoid drugs therapy (for more than 7 consecutive days within the 3 months before enrolment)
10. Individuals with cochlear ear implants
11. Individuals with major cerebrospinal fluid leaks (e.g. following traumatic, major skull surgery, or requiring CSF shunts)
12. Subjects with known or suspected immune deficiency (e.g. HIV, known IgA deficiency, immotile cilia syndrome, or Kartagener’s syndrome)
13. History of frequent nose bleeds
14. Bleeding disorders
15. Significant mental health disorders
16. Other uncontrolled comorbidities, as determined by the clinical investigator, which would be expected to increase the risk of pneumococcal disease
17. Any major pneumococcal illness or pneumonia requiring hospitalisation in the last 10 years
18. Meeting STOP criteria

Medication
1. Any medication that may affect the immune system in the last 3 months (e.g. systemic steroids [IM/IV], steroid nasal spray, Roaccutane, disease-modifying anti-rheumatoid drugs)
2. Long-term antibiotic use or any antibiotics (other than topical) in the past 28 days
3. Recipient of monoclonal antibodies for any indication
4. Recipient of blood transfusion products within the last year
5. Any medication that may affect the coagulation system in the last 3 months (excluding low-dose aspirin)
6. Use of any medication or other product (prescription or over-the-counter) for symptoms of rhinitis or nasal congestion within the last 1 month

Maternity:
1. Pregnancy
2. Lactation
3. Intend t

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
The detection of pneumococcus within nasal epithelial cells, obtained through minimally-invasive superficial nasal scrape biopsies, measured using confocal microscopy and association with nasal colonisation outcome (measured by classical microbiology and multiplex PCR) following pneumococcal inoculation within 28 days from pneumococcal challenge.