Controlled human skin infection with Staphylococcus aureus bacteria in health adult volunteers. Infections and Infestations
Conditions
Interventions
This study is an outpatient, single-centre, single-arm, ambulatory, controlled human infection model (CHIM). The study aims to establish a controlled human skin infection model for Staphylococcus aure
Sponsors
Sheffield Teaching Hospitals NHS Foundation Trust
Eligibility
Sex/Gender
All
Age
18 Years to 55 Years
Inclusion criteria
Inclusion criteria: 1. An informed consent form has been signed and dated by the participant and the Investigator 2. Adults aged between 18 and 55 years inclusive at time of consent 3. In good health as determined by: 3.1. Medical history 3.2. History-directed physical examination 3.3. Screening investigations performed (routine laboratory tests, ECG, echocardiography) 3.4. The clinical judgement of the study team 4. Willing to be available in Sheffield for all required appointments 5. Able and willing (in the study team’s opinion) to comply with all study arrangements, including: 5.1. Availability for all required appointment windows 5.2. Able to use decolonisation treatment as directed 5.3. Willing to adhere to infection control precautions 6. Willing to allow study staff permission to contact their primary care provider to access medical history and to solicit opinion as to appropriateness for inclusion, where needed 7. Willing to allow study staff access to NHS health records as required for study purposes 8. Agree to have 24-hour contact with study staff during the 2-week period after challenge and be able to be contactable by mobile phone for the duration of study and until antimicrobial treatment completion 9. Have internet access to allow completion of the eDiary and real-time safety monitoring 10. Agree to avoid using medicated treatments (including shampoo and shower gel) until advised by a study doctor or until 14 days after challenge 11. Agree to provide their National Insurance/Passport number for the purposes of TOPS registration and for payment of reimbursement expenses
Exclusion criteria
Exclusion criteria: 1. History or evidence of organ dysfunction which could interfere with trial conduct or completion, including but not restricted to: 1.1. Cardiovascular disease, including diagnoses of valvular heart disease, hypertension, or previous episode(s) of infective endocarditis 1.2. Respiratory disease 1.3. Haematological disorders including anaemia felt to be clinically significant by the study team 1.4. Endocrine disease, including known or suspected diabetes mellitus 1.5. Renal or bladder disease 1.6. Autoimmune and metabolic disease 1.7. Psychiatric illness requiring in-patient stay or assessment 1.8. Known or suspected drug or alcohol dependence 1.9. Infectious disease, including personal or family history of severe infections including S. aureus 1.10. acute or chronic dermatologic conditions, including eczema, psoriasis, folliculitis, vitiligo atopic dermatitis and/or keloid scar formation 2. Any genetic, inherited or acquired predisposition that may alter the immune response to S. aureus infection, including a personal or family (first-degree relative) history including severe or invasive staphylococcal infection, Hyper-IgE (Job’s) syndrome (HIES), Chediak-Higashi syndrome, or Wiskott-Aldrich syndrome, IRAK-4 or MYD-88 deficiency, chronic granulomatous disease, HIV infection 3. Presence of implants (except for dental implants) or prosthetic material 4. Family history in 1st degree relative =50 years of age of aneurysmal disease, valvular heart disease, or sudden cardiac or unexplained death 5. Weight less than 50kg and/or a Body Mass Index (BMI) =18kg/m2 and =30kg/m2 6. Venous access deemed inadequate for the phlebotomy demands of the study 7. Scars or tattoos over or near the site of challenge 8. Detection of abnormal results from screening investigations including blood biochemistry, haematology, immunology and urinalysis i.e. grade 1 abnormality or above APPENDIX 6: Grading severity of laboratory results unless deemed not clinically significant and approved by the Principal Investigator. 19. 12-lead electrocardiogram recording with clinically relevant abnormalities, including a prolonged correct QT interval (QTc >450 milliseconds) as judged by a study physician/Principle Investigator 20. Echocardiography demonstrating evidence of structural cardiac abnormalities, in particular relating to valve dysfunction, including hypertrophic cardiomyopathy, rheumatic heart disease, mitral valve prolapse (with regurgitation) and/or mitral annulus calcification, aortic valve disease (regurgitation, stenosis and/or sclerosis), congenital cardiac disease, including aortic stenosis, bicuspid aortic valve, pulmonary stenosis, ventricular septal defect, and patent ductus arteriosus 21. Taking medication, including analgesia, anti-inflammatories or antibiotics that may affect the study integrity, symptom reporting or interpretation of the study results 22. Receipt of blood or blood products, or loss (including blood donations) of =550mL or more of blood during the 3 months prior to the planned date of challenge or planned during the 3 months following the final visit 23. Contraindication to use of: 23.1. Study decolonisation treatment, mupirocin (or naseptin) nasal ointment, chlorhexidine (or octenisan) washes 23.2. Study antimicrobial/antibiotic treatment, hydrogen peroxide or fusidic acid cream, flucloxacillin or clarithromycin (for those who report penicillin allergy) 24. Scheduled elective surgery or other programmed procedures requiring general an
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary. The dose (number colony forming units, CFU) of live S. aureus strain SAUCHAL16 and duration of exposure needed to produce local infection in 60-75% of healthy adult volunteers when administered following microneedle epidermal abrasion measured using the proportion of participants with evidence of local infection at the challenge site (defined as =3/5 SIRS signs/ symptoms with a skin infection rating score of =1, which must include exudate or pus, and a combined total score of =4) and confirmed by microbiological testing of surface swab, pus or microbiopsy (culture or molecular testing) at any time up to 7 days after challenge;Co-primary. The safety and tolerability of skin challenge with live S. aureus strain SAUCHAL16 measured using the proportion of participants experiencing: adverse events, adverse events of special interest, SAEs and concomitant medication usage based on clinical observation, examination findings and participant recording of solicited and unsolicited symptoms at any time during the 7 days before and up to 6 months after challenge | — |
Secondary
| Measure | Time frame |
|---|---|
| Clinical. The S. aureus infection rate when administered following microneedle epidermal abrasion and challenge in healthy adult volunteers at each dose level/exposure duration measured using the proportion of participants at each dose level/ exposure duration with any evidence of local infection at the challenge site (including any SIRS score >0, reported symptoms, or recorded visible skin alterations) at any time up to 14 days after challenge;Clinical. The S. aureus infection rate when administered following microneedle epidermal abrasion and challenge in healthy adult volunteers by baseline S. aureus colonisation status measured using the proportion of participants with evidence of local infection at the challenge site and confirmed by microbiological testing of surface swab, pus or microbiopsy (culture or molecular testing) at any time up to 7 days after challenge;Clinical. The systemic response to S. aureus infection when administered following microneedle epidermal abrasion and challenge in healthy adult volunteers at each dose level/exposure duration and by baseline S. aureus colonisation status measured using the proportion of participants with evidence of systemic signs/symptoms or perturbation of blood test results (full blood count, urea & electrolytes, liver function tests, c-reactive protein) at any time up to 14 days after challenge;Clinical. The severity of S. aureus infection when administered following microneedle epidermal abrasion and challenge in healthy adult volunteers at each dose level/exposure duration and by baseline S. aureus colonisation status measured using the duration of abnormality, median and maximum measurements of symptoms or findings of local infection (SIRS score, other clinical signs/symptoms, or recorded visible skin alteration) and systemic response (any systemic signs/symptoms, or perturbation of blood test results) at any time up to 14 days after challenge;Clinical. The daily change in signs and symptoms related to S. aureu | — |
Countries
England, United Kingdom
Contacts
Public ContactEva Zincone
Outcome results
None listed