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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Atopic Dermatitis; Atopic Dermatitis Eczema; Atopic Dermatitis Flare
• Intervention / Treatment: Drug: Dicloxacillin Oral Capsule; Drug: Elocon 0.1 % Topical Cream

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 Type: Interventional
• Enrollment (Anticipated): 45
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Jacob Thyssen, Professor, MD, DMSc; Phone Number: 38636173; Email: jacob.pontoppidan.thyssen@regionh.dk
• Study Contact Backup: Name: Amalie Rønnstad, MD; Phone Number: 25790995; Email: amalie.thorsti.moeller.roennstad@regionh.dk

Study Locations

• Denmark
  • Copenhagen NV, Denmark, 2100
    • Recruiting
    • Department of Dermatology
    • Contact: Amalie Rønnstad, MD; Phone Number: 25790995; Email: amalie.thorsti.moeller.roennstad@regionh.dk
    • Contact: Jacob Thyssen, MD, Phd, DMSci; Phone Number: 38 63 61 73; Email: jacob.pontoppidan.thyssen@regionh.dk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / 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%

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in The Total Lesion Symptom Scale (TLSS) score improvement	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.	Through study completion, an average of 1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in the skin microbiome measured as community composition (beta-diversity) visualised as PCOA plots	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	1 year
Changes in the skin microbiome measured as alfa-diversity (Shannon diversity)	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	1 year
Changes in the skin microbiome measured as relative abundance (%) of baterial genera	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	1 year
Changes in the amount of cytokines	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	1 year
Changes in itch with peak pruritus 24 hours	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.	Through study completion, an average of 1 year
The effects of treatment on markers of bone resorption and formation with C-terminal telopeptide of type I collagen (CTX)	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.	1 year
The effects of treatment on markers of bone resorption and formation with N-terminal propeptide of type 1 procollagen (P1NP)	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.	1 year
The effects of treatment on markers of bone resorption and formation with parathyroid hormone (PTH)	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.	1 year
Changes in sleep-Numeric rating scale	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.	Through study completion, an average of 1 year
Changes in pain-Numeric rating scale	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.	Through study completion, an average of 1 year
The Eczema Area and Severity Index (EASI)	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.	Through study completion, an average of 1 year

Collaborators and Investigators

• Sponsor: Jacob Pontoppidan Thyssen
• Collaborators: The Novo Nordic Foundation
• Investigators: Principal Investigator: Jacob Thyssen, Professor, MD, DMSc, Professor, Department of Dermatology, Bispebjerg Hospital

Study record dates

Study Major Dates

• Study Start (Actual): October 24, 2022
• Primary Completion (Anticipated): May 1, 2023
• Study Completion (Anticipated): May 1, 2023

Study Registration Dates

• First Submitted: September 30, 2022
• First Submitted That Met QC Criteria: October 10, 2022
• First Posted (Actual): October 13, 2022

Study Record Updates

• Last Update Posted (Actual): December 21, 2022
• Last Update Submitted That Met QC Criteria: December 20, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Keywords: Antibiotics; RCT; Staphylococcus aureus; Atopic dermatitis; Atopic dermatitis flare; Skin microbiome; Skin barrier markers; Topical corticosteroids
• Additional Relevant MeSH Terms: Skin Diseases; Immune System Diseases; Hypersensitivity, Immediate; Genetic Diseases, Inborn; Skin Diseases, Genetic; Hypersensitivity; Skin Diseases, Eczematous; Dermatitis; Eczema; Dermatitis, Atopic; Anti-Infective Agents; Anti-Inflammatory Agents; Dermatologic Agents; Anti-Bacterial Agents; Anti-Allergic Agents; Mometasone Furoate; Dicloxacillin
• Other Study ID Numbers: AR-AB-AD; 2021-006883-25 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: Due to Danish data protection law sharing IPD is not planned. Data outcomes should be anonymized without any recognizable information.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No