Mechanisms of Action of Photo(Chemo)Therapy in Skin Diseases

Study Overview
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Brief Summary
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The molecular mechanisms of action of photo(chemo)therapy in skin diseases are investigated in this study. The phototherapeutic modalities employed include UVB (ultraviolet B), UVA (ultraviolet A), PUVA (psoralen+UVA) and/or extracorporeal photochemotherapy (photopheresis). The study will address whether and how photo(chemo)therapy affects specific biologic pathways in different skin disorders and search for predictive biomarkers.

Detailed Description
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This study is performed in order to investigate the molecular mechanisms of action of photo(chemo)therapy in skin diseases, including psoriasis, cutaneous T-cell lymphoma, other lymphoproliferative disorders of the skin, eczema, lichen planus, prurigo/pruritus, polymorphic light eruption, mastocytosis, graft-versus-host disease, vitiligo and other photo(chemo)therapy-responsive diseases. Twenty patients will be enrolled per diagnosis group. The phototherapeutic modalities administered will be UVB, UVA, PUVA and/or extracorporeal photochemotherapy (photopheresis). The severity of disease and clinical response to treatment will be assessed with scores including dermatological quality of life (DLQI) and disease-specific scores such as PASI (psoriasis area and severity index), mSWAT (modified severity-weighted assessment tool), SCORAD (scoring atopic dermatitis), scleroderma score and/or different visual analog scale (VAS) scores for pruritus. The effect of treatment on a variety of laboratory endpoints will be investigated in blood samples and optionally also skin samples. Those endpoints include among others the regulation of cytokines/chemokines, immune function, clonality of immune cells, vitamin D, and serum lipids. The study will address whether and how photo(chemo)therapy affects specific biologic pathways in the different disorders and determine whether predictive biomarkers for therapeutic response exist.

Official Title
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Explorative Investigations on the Mechanisms of Action of Photo(Chemo)Therapy in Skin Diseases

Conditions
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Eczema, Lichen Planus, Prurigo, Pruritus, Polymorphic Light Eruption, Graft Vs Host Disease, Mastocytosis, Vitiligo, Psoriasis, Cutaneous T Cell Lymphoma, Lymphoproliferative Disorders

Intervention / Treatment
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* Other: Photo(chemo)therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age > 18 years Skin disorder to be treated with photo(chemo)therapy Exclusion Criteria: Pregnancy and breastfeeding Poor general health status

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Interventional Model Description: Biomarker search;
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Other: Photo(chemo)therapy|Treatment with photo(chemo)therapy, including UVB, UVA, PUVA and photopheresis|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Correlation of soluble factors in the serum with clinical response, as measured by disease severity | Serum levels of cytokines, chemokine and other factors, as measured in pg/ml, will be correlated to the clinical response to treatment at the time points specified below to identify potential predictive biomarkers. Disease-specific scores such as PASI, mSWAT, SCORAD, scleroderma score and VAS pruritus scores will be used depending on the condition to carry-out correlation analysis, comparing the change from baseline to end of observation. | Day 14 to 0; week 4; week 8-12; week 12-16 (or month 6-12 for photopheresis) | 
| Correlation of cellular markers of peripheral lymphocytes with clinical response, as measured by disease severity | Expression of cellular markers including CD (cluster of differentiation) 1a, CD3, CD4, CD8, CD11c, CD25, CD45, CD56, CD68, CD103, CD163, FoxP3, as measured by flow cytometry will be correlated to the clinical response to treatment at the time points specified below to identify potential predictive biomarkers. Disease-specific scores such as PASI, mSWAT, SCORAD, scleroderma score and VAS pruritus scores will be used depending on the condition to carry-out correlation analysis, comparing the change from baseline to end of observation. | Day 14 to 0; week 4; week 8-12; week 12-16 (or month 6-12 for photopheresis) | 
| Evaluation of T cell receptor repertoire | Diversity of the T cell repertoire will be assessed by high-throughput sequencing of the T cell receptor and correlated to the clinical response to treatment at the time points specified below to identify its potential predictive value. Disease-specific scores such as PASI, mSWAT, SCORAD, scleroderma score and VAS pruritus scores will be used depending on the condition to carry-out correlation analysis, comparing the change from baseline to end of observation. | Day 14 to 0; week 4; week 8-12; week 12-16 (or month 6-12 for photopheresis) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Vitamin D concentration in serum | Vitamin D levels in serum will be assessed by immunoassay | Day 14 to 0; week 4; week 8-12; week 12-16 (or month 6-12 for photopheresis) | 
| Lipoprotein composition in serum | High density lipoprotein composition in serum will be investigated by proteomics and cholesterol efflux analysis | Day 14 to 0; week 4; week 8-12; week 12-16 (or month 6-12 for photopheresis) | 
| microRNA levels in serum | Levels of micro RNA (133, 206 207, 320, 99a, 150, 197 203 220, 423 and others) will be assessed by microarray assays | Day 14 to 0; week 4; week 8-12; week 12-16 (or month 6-12 for photopheresis) |