Clinical trial NCT04215458: Microbiota in Skin and Mucosa of Patients With Inflammatory Skin Diseases
Official title: Microbiota in Skin and Mucosa of Patients With Inflammatory Skin Diseases
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Fungal Infection
Inflammatory Skin Disease
Yeast Infection Skin
Keywords: fungal colonization
inflammatory skin disease
yeast infection in skin
Lead sponsor: Zealand University Hospital
Sponsor class: OTHER
First posted: 2020-01-02
Enrollment: 700
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: case-control study
Primary purpose: BASIC_SCIENCE

Brief summary: The pathogeneses of many inflammatory diseases are not completely understood, yet, dysregulation of the human microbiota is increasingly being investigated as a possible contributing factor. The human microbiota includes bacteria, archaea, viruses and fungi. In general, little is known about the fungal colonization in inflammatory skin diseases.

This study aims to examine the prevalence of microbiome in skin and oral mucosa of a variety of patients and healthy volunteers visiting the Dermatological outpatient clinic.

The study is designed as a case-control study comparing the incidence of colonization or infection in skin and oral mucosa of patients with different skin diseases and healthy volunteers.

Patients with selected skin diseases, staff at Zealand University Hospital in Roskilde, relatives to staff and students with relation to the Dermatologic Department will be asked to fill out a short questionnaire and have swaps taken from oral mucosa, as well as skin scrapings and tape strips from lesional skin (only patients) and non-lesional skin (all).

Detailed description: Background and aim The pathogeneses of many inflammatory diseases are not completely understood, yet, dysregulation of the human microbiota is increasingly being investigated as a possible contributing factor. The human microbiota includes bacteria, archaea, viruses and fungi. In general, little is known about the fungal colonization in inflammatory skin diseases although Candida species in oral mucosa, skin and feces seem to be increased in patients with psoriasis and atopic dermatitis. Inflammation is also an important part of the pathogenesis in other skin diseases such as hidradenitis suppurativa, acne, vasculitis and inflammatory ulcers. Possibly, increased fungal colonization may be present in many inflammatory skin diseases, yet, this has not previously been investigated. Studies of inflammatory diseases involving other body areas such as systemic lupus erythematosus, Sjögren's disease, multiple sclerosis, and spondyloarthritis have also demonstrated increased colonization with Candida species. However, it is unclear, whether colonization with Candida is a cause or a result of inflammatory disease. Treatment of inflammatory diseases with systemic immune-modulating drugs or recurrent antibiotic therapy may also affect yeast colonization. Emergence of biological therapies that directly or indirectly modulates the Interleukin (IL) 17-pathway emphasizes the need for further knowledge, since the IL-17 pathway is involved in the defense against yeast infections in healthy individuals. Until now, investigations of yeast colonization have primarily focused on Candida and Malassezia. Whether other species of yeasts may be of interest is still uncertain.

This study aims to examine the prevalence of microbiome and infection in skin and oral mucosa of a variety of patients and healthy volunteers visiting the Dermatological outpatient clinic.

Methods Study execution The project is carried out as a collaboration between Dermatological Department, Roskilde University Hospital and Statens Serum Institut (SSI) under the leadership of primary investigator, Senior Doctor in Dermatology, PhD, Ditte Marie Lindhardt Saunte. The project is supported by Medical Doctor in Dermatology, PhD Elisabeth Hjardem Taudorf, Dermatological study nurse Helle Anette Jensen, and the established research group at the Dermatological Department. The samples will be analyzed at SSI at the Dpt. of bacteria, parasites, and fungi under PhD Henrik Vedel Nielsen and Head of Microbial Bioinformatics, Department of Bacteria, Parasites and Fungi, PhD Marc Stegger.

Study design A case-control study comparing the incidence of yeast colonization or infection in skin and oral mucosa of patients with different skin diseases and healthy volunteers. Patients with selected skin diseases, staff at Zealand University Hospital in Roskilde, relatives to staff and students with relation to the Dermatologic Department will be asked to fill out a short questionnaire and have swaps taken from oral mucosa, as well as skin scrapings and tape strips from lesional skin (only patients) and non-lesional skin (all).

Swaps will be examined at Dept. of Microbial Bioinformatics, Department of Bacteria, Parasites and Fungi, Statens Serum Institut. The subgroup of patients initiating systemic therapy for their skin disease at the first examination will be asked to repeat the questionnaire, swaps, skin scrapings and tape strips after approximately three months.

Clinical photos of lesional skin or mucosa will be taken and stored at a secure IT site (Sharepoint and in SP clinical report) after written consent.

Statistics Prevalence and Odds Ratios (OR) will be determined. With a two-sided significance level of 95%, a power of 80 %, an expected ratio of healthy controls vs. patients with skin disease of 0.5 and an expected OR of 2.73 a minimum sample size of 127 patients per skin disease and 64 healthy controls are needed. We aim to include approximately of 130 patients per skin disease. In total, a maximum of 700 individuals will be included, of which 70 will be healthy controls. Inclusion of patients with rare skin diseases may necessitate fewer patients in some groups.

Risks, side effects and drawbacks All samples consist of non-invasive mucosal swaps, skin scrapings or superficial tape strips which holds no risk of known adverse effects. It may be associated with minimal discomfort during sample collection and participants may use an additional 15 minutes of their time in order to receive information regarding the project. Apart from that, this project causes no known risks, side effects or drawbacks.

Biologic material Swaps from mucosal membranes and skin. There is no biobank involved in this project.

Economy The Dermatologic Department, Roskilde University Hospital provides sample materials and Department of Bacteria, Parasites and Fungi, Statens Serum Institute, Copenhagen analyzes the samples. Both departments cover their own expenses. The project is completely independent and does not receive financial support from third parties. None of the involved research workers receive payment for participation or has conflicts of interest related to the project.

Remuneration for trial participants Participants will not receive any remuneration or compensation related to study participation.

Recruitment of trial participants and informed consent Patients, relatives and staff associated to the Dermatologic Department in Roskilde will be asked to participate. Patients and relatives will be recruited during a routine visit to the clinic, while staff will be offered participation during a regular staff meeting. A private consultation will take place, where each participant will receive individual oral and written information about the project in a quiet atmosphere. The participant can bring a bystander and will be offered time for consideration. If requested, an extra interview with repeated possibility to bring a bystander will be provided. If a person wants to participate in the project and meet criteria for inclusion, informed consent will be signed, a short questionnaire filled out and samples will be collected during their regular outpatient visit or by individual appointment.

Publication of results Positive as well as negative results will be published in relevant international Scientific Journals and presented at Scientific meetings and congresses.

Research ethics Many patients, staffs and relatives will be asked to participate in this case-control study, spend a short amount of extra time during an appointment at the clinic and may experience minimal discomfort during collection of samples. In contrast, information about microbiome in different skin diseases may provide a completely new insight and form the basis for further studies to detect the possible causality between microbiome and inflammatory skin diseases. Thus, the potential small disadvantages for project participants can by far be justified by the large amount of new knowledge obtained.

Eligibility criteria: Inclusion Criteria:

* Legally competent women and men
* Age 18 years or older

Exclusion Criteria

* Actual systemic or topical antifungal therapy
* Pregnant or lactating women

Primary outcomes:
measure: prevalence of yeast colonization
timeFrame: at baseline
Secondary outcomes:
measure: subtyping the possible yeasts found on the skin
timeFrame: at baseline
Other outcomes:
Locations:
city: Roskilde
country: Denmark
facility: Zealand University Hospital Roskilde
Study officials:
References: