Molecular Signatures in Inflammatory Skin Disease

Recruiting

• Conditions: Atopic Dermatitis; Psoriasis
• Interventions: Drug: Ustekinumab; Drug: Brodalumab; Drug: Ixekizumab; Drug: Baricitinib; Drug: Infliximab; Drug: Secukinumab; Drug: Dupilumab; Drug: Tralokinumab; Drug: Abrocitinib; Drug: Upadacitinib

• Registration Number: NCT03358693
• Lead Sponsor: Prof. Dr. Stephan Weidinger

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.

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 Timeline

• Study Start: 2017-01-20
• Study First Submitted: 2017-11-04
• Study First Submitted QC: 2017-11-29
• Study First Posted: 2017-11-30
• Status Verified: 2024-12
• Last Update Submitted: 2024-12-03
• Last Update Posted: 2024-12-04
• Primary Completion: 2027-12-31
• Study Completion: 2028-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 300

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.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Psoriasis patients receiving ustekinumab	Ustekinumab	Ustekinumab
Psoriasis patients receiving brodalumab	Brodalumab	Brodalumab
Psoriasis patients receiving Ixekizumab	Ixekizumab	Ixekizumab
Atopic dermatitis patients receiving baricitinib	Baricitinib	Baricitinib
Psoriasis patients receiving infliximab	Infliximab	Infliximab
Psoriasis patients receiving secukinumab	Secukinumab	Secukinumab
Atopic dermatitis patients receiving dupilumab	Dupilumab	Dupilumab
Atopic dermatitis patients receiving tralokinumab	Tralokinumab	Tralokinumab
Atopic dermatitis patients receiving abrocitinib	Abrocitinib	Abrocitinib
Atopic dermatitis patients receiving upadacitinib	Upadacitinib	Upadacitinib

Primary Outcome Measures

Name	Time	Method
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 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 treatment response	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

Secondary Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (1)

Department of Dermatology, University Hospital Schleswig Holstein, Campus Kiel; 🇩🇪 Kiel, Germany