Investigating the early responses to Staphylococcus aureus infection of the skin using a human infection model. The STARS study.
Controlled human skin infection with Staphylococcus aureus bacteria in health adult volunteers.
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 aureus. This model aims to further our understanding of the early responses to skin infection and establish a reproducible platform to develop novel preventative vaccines, therapeutics and early diagnostics. The primary aim is to establish the dose and duration of Staphylococcus aureus (strain SAUCHAL 16) exposure required to develop localised skin infection in 60-75% of healthy adult volunteers when challenged following microneedle epidermal abrasion. A Bayesian continual reassessment method (CRM) will be utilised to conduct dose escalation and determine the optimal challenge dose of SAUCHAL16. A total of 60 eligible, healthy adult volunteers aged 18-55 years will be enrolled after giving informed consent. Volunteers will undergo screening to ensure eligibility for the study. This will include medical history, physical examination, and blood and urine tests to ensure fitness to participate as per the eligibility criteria. Electrocardiogram and echocardiogram will be performed to assess for valvular and structural heart disease. Screening will be undertaken no sooner than 120 days prior to challenge. Participants will be registered on The Over-Volunteering Prevention Database (TOPS). During the pre-challenge phase, participants will self-collect Staphylococcus aureus carriage swabs at fortnightly intervals. These will be taken at home starting 28 days prior to the challenge. Decolonisation will be undertaken 7 days prior to the challenge, consisting of a standard 5-day course of a nasal antibiotic and topical body wash and shampoo. Compliance will be recorded on a daily eDiary, in addition to a paper record log and visual inspection of the packaging after completion by the study team. Baseline investigations will be performed including a punch biopsy, microbiopsies, o
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
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 t