The Pathogenic Role Of Staphylococcus Aureus And The Skin Microbiome During Flare And Resolution Of Atopic Dermatitis
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 发起方
- 入组人数
- 45
- 试验地点
- 1
- 主要终点
- Change in The Total Lesion Symptom Scale (TLSS) score improvement
研究概览
简要总结
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.
详细描述
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?
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
盲法说明
The investigators as well as the participating patients are blinded during the RCT of Dicloxacillin/Placebo & Elocon
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- 未提供
研究组 & 干预措施
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.
干预措施: Dicloxacillin Oral Capsule (Drug)
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.
干预措施: Elocon 0.1 % Topical Cream (Drug)
Placebo & Elocon
20 of the participating patients are randomized to the placebo arm where placebo and elocon creme (mometasone furoate 0.1%) is received.
干预措施: Elocon 0.1 % Topical Cream (Drug)
结局指标
主要结局
Change in The Total Lesion Symptom Scale (TLSS) score improvement
时间窗: 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.
次要结局
- Changes in the skin microbiome measured as community composition (beta-diversity) visualised as PCOA plots(1 year)
- Changes in the skin microbiome measured as alfa-diversity (Shannon diversity)(1 year)
- Changes in the skin microbiome measured as relative abundance (%) of baterial genera(1 year)
- Changes in the amount of cytokines(1 year)
- Changes in itch with peak pruritus 24 hours(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)(1 year)
- The effects of treatment on markers of bone resorption and formation with N-terminal propeptide of type 1 procollagen (P1NP)(1 year)
- The effects of treatment on markers of bone resorption and formation with parathyroid hormone (PTH)(1 year)
- Changes in sleep-Numeric rating scale(Through study completion, an average of 1 year)
- Changes in pain-Numeric rating scale(Through study completion, an average of 1 year)
- The Eczema Area and Severity Index (EASI)(Through study completion, an average of 1 year)
研究者
Jacob Pontoppidan Thyssen
Professor, Jacob Pontoppidan Thyssen
Bispebjerg Hospital