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

Atopic Dermatitis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05578482
• Other study ID #: AR-AB-AD
• Secondary ID: 2021-006883-25
• Status: Recruiting
• Phase: Phase 4
• Start date: October 24, 2022
• Est. completion date: May 2023

Study information

• Verified date: December 2022
• Source: Bispebjerg Hospital
• Contact: Jacob Thyssen, Professor, MD, DMSc
• Phone: 38636173
• Email: jacob.pontoppidan.thyssen[@]regionh.dk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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?

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 45
• Est. completion date: May 2023
• Est. primary completion date: May 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Atopic Dermatitis
• Atopic Dermatitis Eczema
• Dermatitis
• Dermatitis, Atopic
• Eczema

Intervention

Drug:
• Dicloxacillin Oral Capsule
Randomized to either systemic dicloxacillin & elocon or placebo & elocon
• Elocon 0.1 % Topical Cream
Both groups are treated with elocon for five days.

Locations

Country	Name	City	State
Denmark	Department of Dermatology	Copenhagen NV

Sponsors (2)

Lead Sponsor	Collaborator
Jacob Pontoppidan Thyssen	The Novo Nordic Foundation

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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