Clinical trial NCT05578482: Staphylococcus Aureus and The Skin Microbiome During Flare And Resolution Of Atopic Dermatitis
Official title: The Pathogenic Role Of Staphylococcus Aureus And The Skin Microbiome During Flare And Resolution Of Atopic Dermatitis
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Atopic Dermatitis
Atopic Dermatitis Eczema
Atopic Dermatitis Flare
Keywords: Atopic dermatitis
Atopic dermatitis flare
Skin microbiome
Skin barrier markers
RCT
Antibiotics
Topical corticosteroids
Staphylococcus aureus
Lead sponsor: Bispebjerg Hospital
Sponsor class: OTHER
Collaborators: name: The Novo Nordic Foundation
First posted: 2022-10-13
Enrollment: 45
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized Controlled Trial, Double Blinded
Primary purpose: TREATMENT

Brief summary: The goal of this clinical trial is to compare and evaluate in patients with atopic dermatitis. The main questions it aims to answer are:

* Does the addition of systemic dicloxacillin to TCS treatment result in a more rapid and deeper treatment response?
* Does the addition of systemic dicloxacillin to TCS treatment affect the skin microbiome, the skin barrier and immune response during improvement of AD?
* Does topical application of S. aureus or SEB increase the severity and rapidity of a flare?

Participants will meet for two different phases:

* Phase one will be at randomized controlled trial where patients are randomized to either systemic dicloxacillin + mometasone furoate or placebo + mometasone furoate.
* Phase II: Patients will meet for five visits to receive different solutions on the skin including autologous s. aureus and staphylococcal enterotoxin B.

Detailed description: The investigators hypothesize:

Use of oral systemic antibiotic treatment with dicloxacillin (1000 mg x 3 times a day) will decrease the time to AD improvement as well as the amount of S. aureus and its toxins and alter the skin microbiome.

Specifically, the investigators aim to investigate the following research questions:

* RQ1: Does the addition of systemic dicloxacillin to TCS treatment result in a more rapid and deeper treatment response?
* RQ2: Does the addition of systemic dicloxacillin to TCS treatment affect the skin microbiome, the skin barrier and immune response during improvement of AD?
* RQ3: Does topical application of S. aureus or SEB increase the severity and rapidity of a flare?
* RQ4: Does topical application of S. aureus and SEB alter the skin microbiome, the skin barrier and immune response during a flare of AD?
* RQ5: Can changes in protein expression or metabolic pathways explain the modulated mechanisms in the host-microbial cross talk of AD?

Eligibility criteria: Inclusion Criteria:

* Age 18 years or above
* European ancestry
* AD diagnosis according to Hanifin \& Rajka criteria
* AD for at least 3 years
* AD that is moderate-to-severe defined as an EASI score of ≥ 7
* AD in the sampled location that has an TLSS score of ≥ 5

EXCLUSION CRITERIA:

* Current or present systemic immunosuppressant and/or biological treatment for the past 4 weeks
* Evidence of other concomitant inflammatory skin conditions (e.g., psoriasis or contact dermatitis)
* Evidence of active skin infection that warrants treatment at screening or baseline visit
* Systemic or topical antibiotics in the preceding past 4 weeks
* Use of disinfectants, bleach and potassium permanganate baths at least 2 weeks before sampling
* UV therapy within the last 3 weeks, or pronounced exposure to sunlight in the preceding 2 weeks
* History of any condition (e.g. bleeding diathesis) that may predispose the patient to complications associated with the planned skin biopsy procedures
* Other clinically significant medical disease that is uncontrolled despite treatment that is likely, in the opinion of the investigator, to impact the patient's ability to participate in the study or to impact the study pharmacodynamic, or safety assessments
* Decreased kidney function (GFR under 60 ml/min)
* Tendency to formation of keloid scars
* Penicillin or mometasone futurate allergy or intolerance
* Pregnancy
* Breast feeding
* Body weight ≤ 40 kg
* AD only located in the face or intimate regions

Primary outcomes:
measure: Change in The Total Lesion Symptom Scale (TLSS) score improvement
timeFrame: Through study completion, an average of 1 year
Secondary outcomes:
measure: Changes in the skin microbiome measured as community composition (beta-diversity) visualised as PCOA plots
timeFrame: 1 year
measure: Changes in the skin microbiome measured as alfa-diversity (Shannon diversity)
timeFrame: 1 year
measure: Changes in the skin microbiome measured as relative abundance (%) of baterial genera
timeFrame: 1 year
measure: Changes in the amount of cytokines
timeFrame: 1 year
measure: Changes in itch with peak pruritus 24 hours
timeFrame: Through study completion, an average of 1 year
measure: The effects of treatment on markers of bone resorption and formation with C-terminal telopeptide of type I collagen (CTX)
timeFrame: 1 year
measure: The effects of treatment on markers of bone resorption and formation with N-terminal propeptide of type 1 procollagen (P1NP)
timeFrame: 1 year
measure: The effects of treatment on markers of bone resorption and formation with parathyroid hormone (PTH)
timeFrame: 1 year
measure: Changes in sleep-Numeric rating scale
timeFrame: Through study completion, an average of 1 year
measure: Changes in pain-Numeric rating scale
timeFrame: Through study completion, an average of 1 year
measure: The Eczema Area and Severity Index (EASI)
timeFrame: Through study completion, an average of 1 year
Other outcomes:
Locations:
city: Copenhagen NV
country: Denmark
facility: Department of Dermatology
Study officials:
affiliation: Professor, Department of Dermatology, Bispebjerg Hospital
name: Jacob Thyssen, Professor, MD, DMSc
role: PRINCIPAL_INVESTIGATOR
References: