MSID: Molecular Signatures in Inflammatory Skin Disease

Sponsor

Prof. Dr. Stephan Weidinger (Other)

Overall Status

Recruiting

CT.gov ID

NCT03358693

Collaborator

(none)

300

Enrollment

Location

143.3

Anticipated Duration (Months)

2.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This pilot project intends to examine the utility of a systems medicine approach to identify regulatory networks and their perturbation in psoriasis and atopic dermatitis, and to obtain a comprehensive perspective on disease and disease control by integrating and modelling data across multiple cellular levels and time following specific blockade of single pathophysiological factors through use of licensed biologics during routine care as systems biology challenge. To this end, ultra-deep phenotyping and prospective molecular characterization in short time-intervals and different disease equilibrium states will be carried out in targeted small sets of patients. The different layers and types of clinical and molecular information will then be integrated (integrative personal omics profiling iPOP) for generating insights into disease pathways and for extraction of molecular signatures that correspond to clinical severity scores. It will provide a good starting point for planning future trials aimed at identifying biological patterns useful for guiding targeted treatment.

Condition or Disease	Intervention/Treatment	Phase
Atopic Dermatitis Psoriasis	Drug: Ustekinumab Drug: Infliximab Drug: Secukinumab Drug: Dupilumab Drug: Brodalumab Drug: Ixekizumab Drug: Baricitinib Drug: Abrocitinib Drug: Upadacitinib Drug: Tralokinumab

Detailed Description

This is an exploratory study with the aim to identify molecular profiles and signatures in skin and blood that correlate with inflammatory skin disease, disease activity and disease progression, and that are associated with possible disease subtypes/endotypes. Primary target variables are differentially expressed genes (alone or in combination), secondary target variables are genetic, immunological and microbiological signatures. Influencing variables of interest include age of manifestation, disease duration, disease activity/severity, disease progression, comorbidities and therapy/treatment. Obtained biomaterial will be used for molecular profiling including DNA/RNA sequencing, ELISA, mass spectrometry, flow cytometry to identify markers and/or signatures that can correlate with individual disease courses.

Study Design

Study Type:

Observational

Anticipated Enrollment :

300 participants

Observational Model:

Case-Only

Time Perspective:

Prospective

Official Title:

Systematic Profiling of Anti-cytokine Signatures in the Treatment of Chronic Inflammatory Skin Disorders

Actual Study Start Date :

Jan 20, 2017

Anticipated Primary Completion Date :

Dec 31, 2027

Anticipated Study Completion Date :

Dec 31, 2028

Arms and Interventions

Arm	Intervention/Treatment
Psoriasis patients receiving ustekinumab Ustekinumab	Drug: Ustekinumab Subject receives Ustekinumab open-label as per guidelines
Psoriasis patients receiving infliximab Infliximab	Drug: Infliximab Subject receives Infliximab open-label as per guidelines
Psoriasis patients receiving secukinumab Secukinumab	Drug: Secukinumab Subject receives Secukinumab open-label as per guidelines
Atopic dermatitis patients receiving dupilumab Dupilumab	Drug: Dupilumab Subject receives Dupilumab open-label as per guidelines
Psoriasis patients receiving brodalumab Brodalumab	Drug: Brodalumab Subject receives Brodalumab open-label as per guidelines
Psoriasis patients receiving Ixekizumab Ixekizumab	Drug: Ixekizumab Subject receives Ixekizumab open-label as per guidelines
Atopic dermatitis patients receiving tralokinumab Tralokinumab	Drug: Tralokinumab Subject receives Tralokinumab open-label as per guidelines
Atopic dermatitis patients receiving baricitinib Baricitinib	Drug: Baricitinib Subject receives Baricitinib open-label as per guidelines
Atopic dermatitis patients receiving abrocitinib Abrocitinib	Drug: Abrocitinib Subject receives Abrocitinib open-label as per guidelines
Atopic dermatitis patients receiving upadacitinib Upadacitinib	Drug: Upadacitinib Subject receives Upadacitinib open-label as per guidelines

Outcome Measures

Primary Outcome Measures

Changes of molecular profiles over time [Baseline and week 1, week 2, week 12, week 52]
Changes of immune cell composition, transcriptome, proteome and microbiome signatures
Changes of molecular profiles associated with disease severity/remission [Baseline and week 1, week 2, week 12, week 52]
Changes of immune cell composition, transcriptome, proteome and microbiome signatures
Changes of molecular profiles associated with treatment [Baseline and day 1, day 7, day 14, day 84, day 364]
Changes of immune cell composition, transcriptome, proteome and microbiome signatures
Changes of molecular profiles associated with treatment response [Baseline and week 1, week 2, week 12, week 52]
Changes of immune cell composition, transcriptome, proteome and microbiome signatures

Secondary Outcome Measures

Change in Eczema Area and Severity Index (EASI) score [Baseline and week 1, week 2, week 12, week 52]
Clinical severity score
Change in Score of Atopic Dermatitis (SCORAD) [Baseline and week 1, week 2, week 12, week 52]
Clinical severity score
Change in Psoriasis Area Severity Index (PASI) score [Baseline and week 1, week 2, week 12, week 52]
Clinical severity score

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Ability to provide written informed consent and comply with the protocol
Diagnosis of chronic psoriasis or atopic dermatitis
PASI score ≥ 10 or EASI score ≥ 16
Investigator Global Assessment (IGA) ≥ 3
Subject receives systemic therapy within routine care (in-label use of biologics)

Exclusion Criteria:

Subject is unable to provide written informed consent or comply with the protocol.
Having used immunosuppressive/immunomodulating therapy or phototherapy within 4 weeks before the baseline visit.
Treatment of selected skin areas to be examined with topical corticosteroid or topical calcineurin inhibitor within 1 week before the baseline visit.