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

Sponsor

Jacob Pontoppidan Thyssen (Other)

Overall Status

Recruiting

CT.gov ID

NCT05578482

Collaborator

The Novo Nordic Foundation (Other)

Enrollment

Location

Arms

6.2

Anticipated Duration (Months)

7.2

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Atopic Dermatitis Atopic Dermatitis Eczema Atopic Dermatitis Flare	Drug: Dicloxacillin Oral Capsule Drug: Elocon 0.1 % Topical Cream	Phase 4

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?

Study Design

Study Type:

Interventional

Anticipated Enrollment :

45 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Randomized Controlled Trial, Double BlindedRandomized Controlled Trial, Double Blinded

Masking:

Double (Participant, Investigator)

Masking Description:

The investigators as well as the participating patients are blinded during the RCT of Dicloxacillin/Placebo & Elocon

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Oct 24, 2022

Anticipated Primary Completion Date :

May 1, 2023

Anticipated Study Completion Date :

May 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: 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.	Drug: Dicloxacillin Oral Capsule Randomized to either systemic dicloxacillin & elocon or placebo & elocon Other Names: Elocon (Mometasone furoate 0.1%) Drug: Elocon 0.1 % Topical Cream Both groups are treated with elocon for five days. Other Names: Mometasone furoate 0.1%
Placebo Comparator: Placebo & Elocon 20 of the participating patients are randomized to the placebo arm where placebo and elocon creme (mometasone furoate 0.1%) is received.	Drug: Elocon 0.1 % Topical Cream Both groups are treated with elocon for five days. Other Names: Mometasone furoate 0.1%

Arm

Intervention/Treatment

Active Comparator: 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.

Drug: Dicloxacillin Oral Capsule

Randomized to either systemic dicloxacillin & elocon or placebo & elocon

Other Names:

Elocon (Mometasone furoate 0.1%)

Drug: Elocon 0.1 % Topical Cream

Both groups are treated with elocon for five days.

Other Names:

Mometasone furoate 0.1%

Placebo Comparator: Placebo & Elocon

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

Drug: Elocon 0.1 % Topical Cream

Both groups are treated with elocon for five days.

Other Names:

Mometasone furoate 0.1%

Outcome Measures

Primary Outcome Measures

Change in The Total Lesion Symptom Scale (TLSS) score improvement [Through study completion, an average of 1 year]
The primary endpoint is to describe if addition of systemic dicloxacillin treatment (1000 mg x 3 times a day) to topical treatment with mometasone furoate 0.1% cream once daily increases the rapidity and depth of the treatment response measured as changes in The Total Lesion Symptom Scale (TLSS) score improvement. The score is a numerical scale from 0-15.

Secondary Outcome Measures

Changes in the skin microbiome measured as community composition (beta-diversity) visualised as PCOA plots [1 year]
Describe changes in the skin microbiome measured as community composition during i) treatment with systemic dicloxacillin treatment (1000 mg x 3 times a day) and mometasone furoate 0.1% cream once daily ii) treatment with mometasone furoate 0.1% cream once daily iii) cutaneous application of respectively SEB and S. aureus from the patient's self, compared to vehicle
Changes in the skin microbiome measured as alfa-diversity (Shannon diversity) [1 year]
Describe changes in the skin microbiome measured as immune response during i) treatment with systemic dicloxacillin treatment (1000 mg x 3 times a day) and mometasone furoate 0.1% cream once daily ii) treatment with mometasone furoate 0.1% cream once daily iii) cutaneous application of respectively SEB and S. aureus from the patient's self, compared to vehicle
Changes in the skin microbiome measured as relative abundance (%) of baterial genera [1 year]
During i) treatment with systemic dicloxacillin treatment (1000 mg x 3 times a day) and mometasone furoate 0.1% cream once daily ii) treatment with mometasone furoate 0.1% cream once daily iii) cutaneous application of respectively SEB and S. aureus from the patient's self, compared to vehicle
Changes in the amount of cytokines [1 year]
Describe changes in the epidermal barrier disruption through changes in cytokines (to Il-1a, IL-4, IL-13, IL-1RA, CXCL-9, IL-22, IL-31, IL-8, IL-18, CCL-17, CCL-18, CCL-20, CCL-22, CXCL-10, VEGF-A) during i) treatment with systemic dicloxacillin treatment (1000 mg x 3 times a day) and mometasone furoate 0.1% cream once daily ii) treatment with mometasone furoate 0.1% cream once daily iii) cutaneous application of respectively SEB and S. aureus from the patient's self, compared to vehicle
Changes in itch with peak pruritus 24 hours [Through study completion, an average of 1 year]
Changes in itch on a scale from 0-10 during i) treatment with systemic dicloxacillin treatment (1000 mg x 3 times a day) and mometasone furoate 0.1% cream once daily ii) treatment with mometasone furoate 0.1% cream once daily iii) cutaneous application of respectively SEB and S. aureus from the patient's self, compared to vehicle.
The effects of treatment on markers of bone resorption and formation with C-terminal telopeptide of type I collagen (CTX) [1 year]
The investigators aim to investigate the effects of treatment on markers of bone resorption and formation including C-terminal telopeptide of type I collagen (CTX) because TCS such as mometasone furoate may increase bone resorption as seen in a large epidemiologic study.
The effects of treatment on markers of bone resorption and formation with N-terminal propeptide of type 1 procollagen (P1NP) [1 year]
The investigators aim to investigate the effects of treatment on markers of bone resorption and formation including N-terminal propeptide of type 1 procollagen (P1NP) because TCS such as mometasone furoate may increase bone resorption as seen in a large epidemiologic study.
The effects of treatment on markers of bone resorption and formation with parathyroid hormone (PTH) [1 year]
The investigators aim to investigate the effects of treatment on markers of bone resorption and formation including parathyroid hormone (PTH), because TCS such as mometasone furoate may increase bone resorption as seen in a large epidemiologic study.
Changes in sleep-Numeric rating scale [Through study completion, an average of 1 year]
Changes in sleep on a numerical rating scale from 0-10 during: i) treatment with systemic dicloxacillin treatment (1000 mg x 3 times a day) and mometasone furoate 0.1% cream once daily ii) treatment with mometasone furoate 0.1% cream once daily iii) cutaneous application of respectively SEB and S. aureus from the patient's self, compared to vehicle.
Changes in pain-Numeric rating scale [Through study completion, an average of 1 year]
Changes in pain on a numerical rating scale from 0-10 during: i) treatment with systemic dicloxacillin treatment (1000 mg x 3 times a day) and mometasone furoate 0.1% cream once daily ii) treatment with mometasone furoate 0.1% cream once daily iii) cutaneous application of respectively SEB and S. aureus from the patient's self, compared to vehicle.
The Eczema Area and Severity Index (EASI) [Through study completion, an average of 1 year]
Changes in EASI score during: i) treatment with systemic dicloxacillin treatment (1000 mg x 3 times a day) and mometasone furoate 0.1% cream once daily ii) treatment with mometasone furoate 0.1% cream once daily iii) cutaneous application of respectively SEB and S. aureus from the patient's self, compared to vehicle.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts 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