Atopic DermatitisPhase 4NCT05578482
Staphylococcus Aureus and The Skin Microbiome During Flare And Resolution Of Atopic Dermatitis
A Phase 4 study testing Dicloxacillin Oral Capsule and Elocon 0.1 % Topical Cream in people with Atopic Dermatitis and Atopic Dermatitis Eczema, run by Jacob Pontoppidan Thyssen at 1 site in Denmark.
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… Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Atopic Dermatitis, Atopic Dermatitis Eczema, Atopic Dermatitis Flare
- What is being tested?
- Dicloxacillin Oral Capsule and Elocon 0.1 % Topical Cream
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 45 participants
- Where
- 1 siteDenmark
- Study dates
- 24 Oct 2022to May 2023
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 15Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
Denmark1 site, 1 recruiting
- Recruiting
Department of Dermatology
Copenhagen NV, 2100
Jacob Thyssen, MD, Phd, DMSci, 38 63 61 73, jacob.pontoppidan.thyssen@regionh.dk
Amalie Rønnstad, MD, 25790995, amalie.thorsti.moeller.roennstad@regionh.dk
About this study
Official title: 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?
Read more
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.
Read the 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?
- Being tested
- Dicloxacillin Oral Capsule, Elocon 0.1 % Topical Cream
- Keywords
- Atopic dermatitis, Atopic dermatitis flare, Skin microbiome, Skin barrier markers, RCT, Antibiotics, Topical corticosteroids, Staphylococcus aureus
- Medical subject headings
- Dermatitis, Atopic, Staphylococcal Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Dicloxacillin Oral CapsuleDrug
Also called Elocon (Mometasone furoate 0.1%)
Randomized to either systemic dicloxacillin \& elocon or placebo \& elocon
Elocon 0.1 % Topical CreamDrug
Also called Mometasone furoate 0.1%
Both groups are treated with elocon for five days.
| Study group | Role | What they receive |
|---|---|---|
| Dicillin & Elocon | Active comparator | 20 of the participating patients are randomized to the active arm where systemic dicloxacillin and elocon creme (mometasone furoate 0.1%) is received. Receives: Drug: Dicloxacillin Oral Capsule; Drug: Elocon 0.1 % Topical Cream |
| Placebo & Elocon | Placebo comparator | 20 of the participating patients are randomized to the placebo arm where placebo and elocon creme (mometasone furoate 0.1%) is received. Receives: Drug: Elocon 0.1 % Topical Cream |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Through study completion, an average of 1 year
Secondary outcomes (11)
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
Measured: 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
Measured: 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
Measured: 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
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Through study completion, an average of 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Oct 2022
- Study start24 Oct 2022
- Primary completionMay 2023 (estimated)
- Study completionMay 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Atopic DermatitisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Randomized Controlled Trial, Double Blinded
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 45 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Jacob Pontoppidan Thyssen
- Sponsor type
- University, hospital or other
- Collaborators
- The Novo Nordic Foundation
- Responsible party
- Sponsor-investigator, Jacob Pontoppidan Thyssen, Bispebjerg Hospital
- Investigators
- Jacob Thyssen, Professor, MD, DMSc, Principal investigator, Professor, Department of Dermatology, Bispebjerg Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05578482
- Sponsor's protocol ID
- AR-AB-AD
- Other IDs
- 2021-006883-25
- Status last verified
- Dec 2022
- First submitted
- 30 Sep 2022
- Last updated
- 21 Dec 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Due to Danish data protection law sharing IPD is not planned. Data outcomes should be anonymized without any recognizable information.
Publications
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.
PubMed 36806068
Study at a glance
From the registry record, last updated by the sponsor on 21 Dec 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Pathogenic Role Of Staphylococcus Aureus And The Skin Microbiome During Flare And Resolution Of Atopic Dermatitis
- ClinicalTrials.gov ID
- NCT05578482
- Acronym / sponsor ID
- AR-AB-AD
- Keywords
- Atopic dermatitis, Atopic dermatitis flare, Skin microbiome, Skin barrier markers, RCT, Antibiotics, Topical corticosteroids, Staphylococcus aureus
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 45 participants (estimated)
- Lead sponsor
- Jacob Pontoppidan ThyssenUniversity, hospital or other
- Collaborators
- The Novo Nordic Foundation
- Study start
- 24 Oct 2022 (actual)
- Primary completion
- May 2023 (estimated)
- Study completion
- May 2023 (estimated)
- First posted
- 13 Oct 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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?
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
- Model description
- Randomized Controlled Trial, Double Blinded
| Arm | Type | Receives |
|---|---|---|
| Dicillin & Elocon | Active comparator | Drug: Dicloxacillin Oral Capsule, Drug: Elocon 0.1 % Topical Cream20 of the participating patients are randomized to the active arm where systemic dicloxacillin and elocon creme (mometasone furoate 0.1%) is received. |
| Placebo & Elocon | Placebo comparator | Drug: Elocon 0.1 % Topical Cream20 of the participating patients are randomized to the placebo arm where placebo and elocon creme (mometasone furoate 0.1%) is received. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (15 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Dicloxacillin Oral CapsuleAlso: Elocon (Mometasone furoate 0.1%)Randomized to either systemic dicloxacillin \& elocon or placebo \& elocon | Drug | Dicillin & Elocon |
| Elocon 0.1 % Topical CreamAlso: Mometasone furoate 0.1%Both groups are treated with elocon for five days. | Drug | Dicillin & Elocon, Placebo & Elocon |
Primary outcome
Change in The Total Lesion Symptom Scale (TLSS) score improvement
Time frame: 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.
11 secondary outcomes
Changes in the skin microbiome measured as community composition (beta-diversity) visualised as PCOA plots
Time frame: 1 year
Changes in the skin microbiome measured as alfa-diversity (Shannon diversity)
Time frame: 1 year
Changes in the skin microbiome measured as relative abundance (%) of baterial genera
Time frame: 1 year
Changes in the amount of cytokines
Time frame: 1 year
Changes in itch with peak pruritus 24 hours
Time frame: 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)
Time frame: 1 year
The effects of treatment on markers of bone resorption and formation with N-terminal propeptide of type 1 procollagen (P1NP)
Time frame: 1 year
The effects of treatment on markers of bone resorption and formation with parathyroid hormone (PTH)
Time frame: 1 year
Changes in sleep-Numeric rating scale
Time frame: Through study completion, an average of 1 year
Changes in pain-Numeric rating scale
Time frame: Through study completion, an average of 1 year
The Eczema Area and Severity Index (EASI)
Time frame: Through study completion, an average of 1 year
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Dec 2022.
- Derived from this study: PubMed 36806068Ronnstad 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.
- Individual participant dataSharing planned: No. Due to Danish data protection law sharing IPD is not planned. Data outcomes should be anonymized without any recognizable information.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jacob Thyssen, Professor, MD, DMSc principal investigator
Professor, Department of Dermatology, Bispebjerg Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Dicloxacillin Oral Capsule and Elocon 0.1 % Topical Cream in people with Atopic Dermatitis and Atopic Dermatitis Eczema, run by Jacob Pontoppidan Thyssen at 1 site in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 21 Dec 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Jacob Thyssen, Professor, MD, DMSc (38636173, jacob.pontoppidan.thyssen@regionh.dk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in The Total Lesion Symptom Scale (TLSS) score improvement (time frame: Through study completion, an average of 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05578482, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Dec 2022.