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

NCT ID: NCT05578482

Last Updated: 2022-12-21

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 45 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-10-24
• Study Completion Date: 2023-05-31

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?

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Dicillin & Elocon

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

Group Type: ACTIVE_COMPARATOR

Dicloxacillin Oral Capsule

Intervention Type: DRUG

Randomized to either systemic dicloxacillin \& elocon or placebo \& elocon

Elocon 0.1 % Topical Cream

Intervention Type: DRUG

Both groups are treated with elocon for five days.

Placebo & Elocon

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

Group Type: PLACEBO_COMPARATOR

Elocon 0.1 % Topical Cream

Intervention Type: DRUG

Both groups are treated with elocon for five days.

Interventions

Dicloxacillin Oral Capsule

Randomized to either systemic dicloxacillin \& elocon or placebo \& elocon

Intervention Type: DRUG

Elocon 0.1 % Topical Cream

Both groups are treated with elocon for five days.

Intervention Type: DRUG

Other Intervention Names

Elocon (Mometasone furoate 0.1%); Mometasone furoate 0.1%

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The Novo Nordic Foundation

OTHER

Sponsor Role: collaborator

Jacob Pontoppidan Thyssen

OTHER

Sponsor Role: lead

Responsible Party

Jacob Pontoppidan Thyssen

Professor, Jacob Pontoppidan Thyssen

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Jacob Thyssen, Professor, MD, DMSc

Role: PRINCIPAL_INVESTIGATOR

Professor, Department of Dermatology, Bispebjerg Hospital

Locations

Department of Dermatology

Copenhagen NV, , Denmark

Site Status: RECRUITING

Countries

Denmark

Central Contacts

Jacob Thyssen, Professor, MD, DMSc

Role: CONTACT

Phone: 38636173

Email: jacob.pontoppidan.thyssen@regionh.dk

Amalie Rønnstad, MD

Role: CONTACT

Phone: 25790995

Email: amalie.thorsti.moeller.roennstad@regionh.dk

Facility Contacts

Jacob Thyssen, MD, Phd, DMSci

Role: primary

Amalie Rønnstad, MD

Role: backup

References

Ronnstad ATM, Bay L, Ruge IF, Halling AS, Fritz BG, Jakasa I, Luiten R, Kezic S, Thomsen SF, Bjarnsholt T, Thyssen JP. Defining the temporal relationship between the skin microbiome, immune response and skin barrier function during flare and resolution of atopic dermatitis: protocol of a Danish intervention study. BMJ Open. 2023 Feb 17;13(2):e068395. doi: 10.1136/bmjopen-2022-068395.

Reference Type: DERIVED

PMID: 36806068 (View on PubMed)

Other Identifiers

2021-006883-25

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

AR-AB-AD

Identifier Type: -

Identifier Source: org_study_id