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

Primary Purpose

Atopic Dermatitis, Atopic Dermatitis Eczema, Atopic Dermatitis Flare

Status
Recruiting
Phase
Phase 4
Locations
Denmark
Study Type
Interventional
Intervention
Dicloxacillin Oral Capsule
Elocon 0.1 % Topical Cream
Sponsored by
Jacob Pontoppidan Thyssen
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Atopic Dermatitis focused on measuring Atopic dermatitis, Atopic dermatitis flare, Skin microbiome, Skin barrier markers, RCT, Antibiotics, Topical corticosteroids, Staphylococcus aureus

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

  • Department of DermatologyRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Dicillin & Elocon

Placebo & Elocon

Arm Description

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

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

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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
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
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
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
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.
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.
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.
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.
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.
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.
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.

Full Information

First Posted
September 30, 2022
Last Updated
December 20, 2022
Sponsor
Jacob Pontoppidan Thyssen
Collaborators
The Novo Nordic Foundation
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1. Study Identification

Unique Protocol Identification Number
NCT05578482
Brief Title
Staphylococcus Aureus and The Skin Microbiome During Flare And Resolution Of Atopic Dermatitis
Official Title
The Pathogenic Role Of Staphylococcus Aureus And The Skin Microbiome During Flare And Resolution Of Atopic Dermatitis
Study Type
Interventional

2. Study Status

Record Verification Date
December 2022
Overall Recruitment Status
Recruiting
Study Start Date
October 24, 2022 (Actual)
Primary Completion Date
May 2023 (Anticipated)
Study Completion Date
May 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Jacob Pontoppidan Thyssen
Collaborators
The Novo Nordic Foundation

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. 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.
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?

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Model Description
Randomized Controlled Trial, Double Blinded
Masking
ParticipantInvestigator
Masking Description
The investigators as well as the participating patients are blinded during the RCT of Dicloxacillin/Placebo & Elocon
Allocation
Randomized
Enrollment
45 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Dicillin & Elocon
Arm Type
Active Comparator
Arm Description
20 of the participating patients are randomized to the active arm where systemic dicloxacillin and elocon creme (mometasone furoate 0.1%) is received.
Arm Title
Placebo & Elocon
Arm Type
Placebo Comparator
Arm Description
20 of the participating patients are randomized to the placebo arm where placebo and elocon creme (mometasone furoate 0.1%) is received.
Intervention Type
Drug
Intervention Name(s)
Dicloxacillin Oral Capsule
Other Intervention Name(s)
Elocon (Mometasone furoate 0.1%)
Intervention Description
Randomized to either systemic dicloxacillin & elocon or placebo & elocon
Intervention Type
Drug
Intervention Name(s)
Elocon 0.1 % Topical Cream
Other Intervention Name(s)
Mometasone furoate 0.1%
Intervention Description
Both groups are treated with elocon for five days.
Primary Outcome Measure Information:
Title
Change in The Total Lesion Symptom Scale (TLSS) score improvement
Description
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.
Time Frame
Through study completion, an average of 1 year
Secondary Outcome Measure Information:
Title
Changes in the skin microbiome measured as community composition (beta-diversity) visualised as PCOA plots
Description
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
Time Frame
1 year
Title
Changes in the skin microbiome measured as alfa-diversity (Shannon diversity)
Description
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
Time Frame
1 year
Title
Changes in the skin microbiome measured as relative abundance (%) of baterial genera
Description
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
Time Frame
1 year
Title
Changes in the amount of cytokines
Description
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
Time Frame
1 year
Title
Changes in itch with peak pruritus 24 hours
Description
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.
Time Frame
Through study completion, an average of 1 year
Title
The effects of treatment on markers of bone resorption and formation with C-terminal telopeptide of type I collagen (CTX)
Description
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.
Time Frame
1 year
Title
The effects of treatment on markers of bone resorption and formation with N-terminal propeptide of type 1 procollagen (P1NP)
Description
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.
Time Frame
1 year
Title
The effects of treatment on markers of bone resorption and formation with parathyroid hormone (PTH)
Description
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.
Time Frame
1 year
Title
Changes in sleep-Numeric rating scale
Description
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.
Time Frame
Through study completion, an average of 1 year
Title
Changes in pain-Numeric rating scale
Description
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.
Time Frame
Through study completion, an average of 1 year
Title
The Eczema Area and Severity Index (EASI)
Description
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.
Time Frame
Through study completion, an average of 1 year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jacob Thyssen, Professor, MD, DMSc
Phone
38636173
Email
jacob.pontoppidan.thyssen@regionh.dk
First Name & Middle Initial & Last Name or Official Title & Degree
Amalie Rønnstad, MD
Phone
25790995
Email
amalie.thorsti.moeller.roennstad@regionh.dk
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jacob Thyssen, Professor, MD, DMSc
Organizational Affiliation
Professor, Department of Dermatology, Bispebjerg Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Department of Dermatology
City
Copenhagen NV
ZIP/Postal Code
2100
Country
Denmark
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jacob Thyssen, MD, Phd, DMSci
Phone
38 63 61 73
Email
jacob.pontoppidan.thyssen@regionh.dk
First Name & Middle Initial & Last Name & Degree
Amalie Rønnstad, MD
Phone
25790995
Email
amalie.thorsti.moeller.roennstad@regionh.dk

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing Plan Description
Due to Danish data protection law sharing IPD is not planned. Data outcomes should be anonymized without any recognizable information.

Learn more about this trial

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

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