Staphylococcus Aureus and The Skin Microbiome During Flare And Resolution Of Atopic Dermatitis

Jacob Pontoppidan Thyssen

Status and phase: Enrolling; Phase 4

Conditions: Atopic Dermatitis; Atopic Dermatitis Flare; Atopic Dermatitis Eczema

Treatments: Drug: Dicloxacillin Oral Capsule; Drug: Elocon 0.1 % Topical Cream

Study type: Interventional

Funder types: Other

Identifiers

NCT05578482

2021-006883-25 (EudraCT Number)

AR-AB-AD

Details and patient eligibility

About

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.

Full 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?

Enrollment: 45 estimated patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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45 participants in 2 patient groups, including a placebo group

Dicillin & Elocon

Active Comparator group

Description:

20 of the participating patients are randomized to the active arm where systemic dicloxacillin and elocon creme (mometasone furoate 0.1%) is received.

Treatment:

Drug: Elocon 0.1 % Topical Cream

Drug: Dicloxacillin Oral Capsule

Placebo & Elocon

Placebo Comparator group

Description:

20 of the participating patients are randomized to the placebo arm where placebo and elocon creme (mometasone furoate 0.1%) is received.

Treatment:

Drug: Elocon 0.1 % Topical Cream