Study of Skin Microbiome in AD and PS Patients

Longitudinal "Real-World" Changes in Skin Microbial Ecology in Atopic Dermatitis (AD) and Psoriasis (PS) Patients

Everybody's skin has bacteria that normally lives on it. Previous research has shown that people with eczema (or atopic dermatitis [AD]) have much higher concentrations of a certain bacteria (S. aureus), especially when their disease is active but little is known about the role that this bacteria plays in psoriasis (i.e. disease severity, biomarkers and skin barrier function). The overarching purpose of this longitudinal study is to understand how the abundance of skin S. aureus (and several commensal bacteria) change as a consequence of standard of care treatment in the URMC dermatology clinics. Other assays and biospecimens will also be collected to address a number of questions.

Study Overview

• Status: Recruiting
• Conditions: Psoriasis; Atopic Dermatitis
• Intervention / Treatment: Other: Skin swab, TEWL with tape stripping, and serum (adults)

Detailed Description

We believe that as this skin diseases (AD and Psoriasis) are effectively managed with topical and/or systemic therapies, the levels of C. acnes (and/or production of lantibiotics) will increase and this will subsequently be followed by reductions in S. aureus and these changes will be reflected in skin barrier improvements and changes in biomarkers. We have several aims.

Aim 1 - Determine how the abundance (assessed by polymerase chain reaction [PCR]) of S. aureus, other relevant coagulase-negative Staphylococcus species [CONS], and C. acnes on the skin surface varies as a function of time and/or disease activity in AD, plaque stage psoriasis (PS) and healthy, non-atopics (NA).

Aim 2 - Validate whether a serum biomarker (or panel) identifies subjects with greater S. aureus burden (e.g., abundance).

Aim 3 - Identify a serum biomarker (or panel) that predicts clinical improvement observed in our AD subjects.

Aim 4 - Quantify S. aureus virulence factors from skin swabs of all three subject populations.

Aim 5 - Develop a skin bacterial repository (optional). Aim 5.1 - Specifically focus on a repository of S. aureus, C. acnes, and CONS isolates from AD and PS patients, and age- and gender-matched healthy NAs.

Aim 5.2 - Determine if C. acnes isolates obtained from skin swabs of AD, PS, and NA patients exhibit anti-S. aureus properties in vitro by monitoring S. aureus growth curves in response to exposure to C. acnes or C. acnes-conditioned media.

Aim 5.3 - Perform whole genome DNA sequencing of C. acnes isolates from all patients to analyze whether C. acnes' genome harbors distinct gene(s) that correlate with the anti- S. aureus properties observed in Aim 5.2.

Aim 6 - Develop a repository of skin tape strips for biomarker and protease assays.

• Study Type: Observational
• Enrollment (Estimated): 230

Contacts and Locations

• Study Contact: Name: Kimberly Leffler; Phone Number: 585-273-4195; Email: kimberly_leffler@urmc.rochester.edu

Study Locations

• United States
  • New York
    • Rochester, New York, United States, 14642
      • Recruiting
      • University of Rochester Medical Center
      • Contact: Lisa Beck, MD; Phone Number: 585-275-7546; Email: lisa_beck@urmc.rochester.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 13 years to 65 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

The healthy population will be defined as individuals with no personal history of or active case of any atopic disorder (e.g. atopic dermatitis, allergic rhinitis, asthma, hay fever). These patients will be individuals seen in URMC Dermatology clinic for a non-infectious condition that does not affect the skin of the extremities.

AD subjects must have moderate-to-severe disease defined as an Eczema Area and Severity Index (EASI) of ≥ 12. The psoriasis subjects will have moderate-to-severe disease defined as a Psoriasis Area and Severity Index of ≥ 7. The healthy controls will be recruited to be age- and gender-matched to those with inflammatory skin diseases. Subjects will be recruited from URMC Dermatology clinics at Red Creek and Collegetown.

Description

Inclusion Criteria:

• ≥13 to 65 years of age (inclusive), male or female; can be 65+ in AD cohort
• Able to understand protocol and give consent
• Able to keep clinic/study appointments and comply with study related procedures
• Must be able to read, speak, and understand English
• Chronic AD, according to the American Academy of Dermatology (AAD) Consensus Criteria, that has been present for at least 1 year before the enrollment visit
• Chronic PS, according to the AAD Consensus Criteria, that has been present for at least 1 year before the enrollment visit.
• AD subjects: have active lesions on upper extremities, lower extremities, or trunk and a total disease severity of high moderate-to-severe (EASI ≥12)
• PS subjects: have active lesions on upper extremities, lower extremities, or trunk and a total disease severity of high moderate-to-severe (PASI ≥7)

Exclusion Criteria:

• Unwilling and/or unable to complete informed consent process
• <13 or > 65 years of age
• AD subjects: disease without upper extremity, lower extremity, or trunk lesions
• AD subjects: total disease severity less than moderate (EASI <12), depending on enrollment
• PS subjects: disease without upper extremity, lower extremity, or trunk lesions
• PS subjects: total disease severity less than moderate (PASI <7), depending on enrollment
• Control subjects: diagnosed with an inflammatory skin disease and/or history of atopy (atopic dermatitis, allergic rhinitis, asthma, hay fever)
• Severe concomitant illness(es) that, in the investigator's judgment, would adversely affect the individual's participation in the study (Ex: HIV infection, autoimmune disease, severe heart failure, Hx of malignancy (other than in situ cervical cancer or basosquamous skin cancer), etc.)
• Recent bacterial, fungal, or viral infection requiring systemic therapies (PO, IV or IM) within the last month.
• Patients with a history of serious life-threatening reaction to tape or adhesives may be enrolled but cannot undergo transepidermal water loss (TEWL) measurements.
• AD subjects 18 years or older and healthy control subjects only: unwilling and/or unable to undergo 30-cc blood draw

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Healthy control; No intervention Ages:13-65 yrs of age, all genders, races and ethnicities	Other: Skin swab, TEWL with tape stripping, and serum (adults); Skin will be swabbed to collect samples for bacterial analysis. Transepidermal water loss (TEWL) will be measured at 4 time points: before tape stripping, after application of 5 D-squame tapestrips, after application of 10 D-squame tapestrips, and after application of 15 D-squame tapestrips (total tapestrips per site = 15).; Other Names: skin barrier function
Psoriasis; Intervention is whatever Rx the URMC dermatologist thinks is best suited to the subject as part of "real-world" disease management in her clinic. Ages:13-65 yrs of age, all genders, races and ethnicities	Other: Skin swab, TEWL with tape stripping, and serum (adults); Skin will be swabbed to collect samples for bacterial analysis. Transepidermal water loss (TEWL) will be measured at 4 time points: before tape stripping, after application of 5 D-squame tapestrips, after application of 10 D-squame tapestrips, and after application of 15 D-squame tapestrips (total tapestrips per site = 15).; Other Names: skin barrier function
Atopic Dermatitis; Intervention is whatever Rx the URMC dermatologist thinks is best suited to the subject as part of "real-world" disease management in her clinic.; Ages:13-65 yrs of age, all genders, races and ethnicities; Additional 65+ age group, all genders, races and ethnicities	Other: Skin swab, TEWL with tape stripping, and serum (adults); Skin will be swabbed to collect samples for bacterial analysis. Transepidermal water loss (TEWL) will be measured at 4 time points: before tape stripping, after application of 5 D-squame tapestrips, after application of 10 D-squame tapestrips, and after application of 15 D-squame tapestrips (total tapestrips per site = 15).; Other Names: skin barrier function

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Abundance of colony forming units of Cutibacterium acnes (C. acnes)	Skin swabs will be collected and cultured in anaerobic and aerobic conditions in the laboratory. The number of colonies of Cutibacterium acnes, Staphylococcus aureus and other coagulase-negative Staphylococci will be counted. The proportion of C. acnes relative to the other bacteria counted will be calculated.	year 3
Abundance of colony forming units of Staphylococcus aureus (S. aureus)	Skin swabs will be collected and cultured in anaerobic and aerobic conditions in the laboratory. The number of colonies of Cutibacterium acnes, Staphylococcus aureus and other coagulase-negative Staphylococci will be counted. The proportion of S. aureus relative to the other bacteria counted will be calculated.	year 3

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Identify serum biomarker (or biomaker panel) that associates with disease severity or S. aureus abundance	Serum collected longitudinally will be measured by a multianalyte method	Years 3-5
Measure S. aureus virulence factors from skin swabs	We will determine whether any one or panel of these S. aureus virulence factors associate with AD or PS severity, barrier function or serum biomarkers	Years 3-5
Measure host/patient biomarkers from skin tape strips (or skin swabs)	We will evaluate whether host response to bacteria are increased in tape strips or skin swabs as a function of reductions in S. aureus abundance.	Years 3-5

Collaborators and Investigators

• Sponsor: University of Rochester
• Investigators: Principal Investigator: Lisa A Beck, MD, University of Rochester

Study record dates

Study Major Dates

• Study Start (Actual): April 17, 2019
• Primary Completion (Estimated): April 1, 2024
• Study Completion (Estimated): April 1, 2024

Study Registration Dates

• First Submitted: November 18, 2019
• First Submitted That Met QC Criteria: November 18, 2019
• First Posted (Actual): November 20, 2019

Study Record Updates

• Last Update Posted (Actual): March 25, 2024
• Last Update Submitted That Met QC Criteria: March 22, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: staphylococcus, microbiome, atopic dermatitis, cutibacterium
• Additional Relevant MeSH Terms: Skin Diseases; Immune System Diseases; Hypersensitivity, Immediate; Genetic Diseases, Inborn; Skin Diseases, Genetic; Skin Diseases, Papulosquamous; Hypersensitivity; Skin Diseases, Eczematous; Psoriasis; Dermatitis; Eczema; Dermatitis, Atopic
• Other Study ID Numbers: 3830

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No