Cellulitis Skin and Connective Tissue Diseases
Conditions
Interventions
In total, up to 40 participants will be recruited (20 to the recent SSTI cohort and 20 to the healthy participant cohort). After the provision of written informed consent and completion of screening p
Sponsors
Sheffield Teaching Hospitals NHS Foundation Trust
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: All participants: Participants are eligible to be included in the study only if all of the following criteria apply: 1. Adults aged =18 years at time of consent 2. Willing and able to provide written informed consent and to comply with the study requirements, according to the investigator’s opinion 3. Agree to provide their National Insurance/Passport number for the purposes of payment of reimbursement expenses 4. Have internet access to allow completion of the e-Diary 5. Be in good general health as determined by medical history, history-directed physical examination, screening investigations performed, and the clinical judgement of the study team SSTI cohort: In addition, for the recent SSTI cohort: 1. Have had a recent SSTI probably (i.e. no alternative microbiological diagnosis with a compatible clinical syndrome) or definitely (i.e. confirmed by microbiological laboratory testing) caused by S. aureus infection diagnosed within the 6 months preceding the screening visit appointment 2. Agree to allow study staff to access their NHS health records (including hospital notes and laboratory records) as required for study purposes
Exclusion criteria
Exclusion criteria: Participants are excluded from the study if any of the following criteria apply: 1. History or evidence of: 1.1. Chronic dermatological conditions, including eczema, psoriasis, folliculitis, vitiligo, tinea corporis, and atopic dermatitis 1.2. Abnormal or impaired immune function, including congenital or acquired immunodeficiency, or receipt of immunosuppressive therapy, including oral/inhaled corticosteroids, chemo-/radiotherapy, or monoclonal antibody treatment 1.3. Peripheral vascular (arterial and/or venous) disease 1.4. Clinically significant bleeding disorder, including clotting factor deficiency, coagulopathy, platelet disorder, or current anaemia 1.5. Active cancer/malignancy 2. Active skin or soft tissue infection 3. A history of keloid scarring 4. Any condition that, in the opinion of the Investigator, might compromise participant safety or interfere with the evaluation of the study intervention or interpretation of participant safety or study results 5. Inability to comply with any of the study requirements (at the discretion of study staff) 6. Significant blood donation or recent blood (/blood product) donation to NHS Blood and Transplant Service (within 90 days) 7. Tattoos or scarring to the forearm where OCT imaging/NPSB/microneedle assessment procedures will be performed 8. Volunteer incapable of giving fully informed consent Temporary Exclusion: Participants will be temporarily excluded from study procedures at V1 and V2 if presenting with the following: 1. Significant acute or acute-on-chronic infection within the previous 7 days or have experienced fever (>37.5°C) or subjective febrile symptoms within the previous 3 days (even with a negative COVID-19 test) 2. History of any antibiotic therapy during the previous 5 days 3. Any systemic corticosteroid (or equivalent) treatment in the previous 14 days, or for more than seven consecutive days within the past 3 months 4. Anaemia felt to be clinically significant by the study team 5. Receipt of any vaccine including SARS-CoV2 vaccines in the 28 days before or during the study period (D1-D28) 6. Participants meeting any of the temporary exclusion criteria on the day of the challenge will be deferred to a later date for a rescreening appointment, as agreed by the study team and Principal Investigator
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Combined abundance of immune cell populations in NPSB fluid collected at 2 visits 3 weeks apart (V1/V4), measured by single-cell RNA sequencing (scRNA-seq) within 6 months of an SSTI episode | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Abundance of immune cell populations in peripheral blood (PBMC) collected at baseline (V1) measured using flow-cytometry within 6 months of an SSTI episode 2. Measurement of IgG antibodies to S. aureus antigens (hlA, clfA, SpA, capsular polysaccharide 5/8) in peripheral blood collected at baseline (V1) measured by multiplex bead array within 6 months of an SSTI episode 3. Combined abundance of immune cell populations in NPSB fluid collected at 2 visits 3 weeks apart (V1/V4) stratified by S. aureus carriage status and measured by scRNA-seq within 6 months of an SSTI episode 4. Skin surface texture, epidermal thickness, depth/morphology of the superficial vascular plexus, optical attenuation measured using OCT imaging at baseline (V1) 5. Microneedle disruption including tissue fluid volume and hole closure kinetics measured at visit 4 using OCT images collected 10, 30 and 60 minutes following microneedle application 6. Subjective participant pain and healing response to study procedures performed at two visits 3 weeks apart (V1/V4) measured using Visual Analog Scale (VAS) and Patient and Observer Scar Assessment Scale (POSAS), respectively 7. Diversity and abundance of skin bacterial populations collected by skin swab at baseline (V1) measured using 16s rRNA sequencing analysis or hs-PCR measurements within 6 months of an SSTI episode | — |
Countries
England, United Kingdom
Contacts
Public ContactLaura Makey
Outcome results
None listed