An Explorative Psoriasis Biomarker Study
- Registration Number
- NCT04394936
- Lead Sponsor
- Centre for Human Drug Research, Netherlands
- Brief Summary
Plaque psoriasis may be an ideal model disease to explore potential therapeutic effects of immunosuppressive agents, given the easy accessibility of inflammatory lesions. In this study, the applicability of a systems dermatology approach is investigated in order to better assess the efficacy of psoriasis treatments at an early clinical stage. Up to this point, the clinical manifestation and regression of psoriasis is not yet sufficiently characterized with a multimodal state-of-the-art evaluation tool. The in-house developed 'DermaToolbox' enables the determination and subsequent integration of different diseaserelated biomarkers, including clinical, biophysical, molecular, cellular, and imaging markers as well as patient reported outcomes
- Detailed Description
Psoriasis is a common skin disorder affecting up to an estimated 3% of the world's population. The most prevalent form of psoriasis, called psoriasis vulgaris or plaque psoriasis, is characterized by the presence of sharply demarcated erythematous plaques covered with white scales. These lesions can occur all over the body, but are most often seen on the extensor surface of the joints, nether regions and on the scalp. Patients can experience excessive itch, pain and sometimes bleeding of the lesions. Moreover, the visual appearance of psoriatic lesions can severely impact the patients psychological state and quality of life. An abundancy of different factors contributes to the pathogenesis of psoriasis. However, aberrant inflammatory reactions in the skin are thought to be the underlying cause. Excessive infiltration of immune cells in the skin and their interactions with cutaneous resident cells results in the hyper proliferation of keratinocytes and subsequent thickening of the epidermis. Indeed, more and more immunosuppressive biologicals targeting specific components of the immune system, like tumor necrosis factor alpha (TNFα), interleukin (IL-)17 and IL-23, have shown excellent efficacy in treating psoriasis Plaque psoriasis may be an ideal model disease to explore potential therapeutic effects of immunosuppressive agents, given the easy accessibility of inflammatory lesions and the good willingness of patients to participate in clinical studies. In this study, the applicability of a systems dermatology approach is investigated in order to better assess the efficacy of psoriasis treatments at an early clinical stage. Up to this point, the clinical manifestation and regression of psoriasis is not yet sufficiently characterized with a multimodal state-of-the-art evaluation tool. The in-house developed 'DermaToolbox' enables the determination and subsequent integration of different disease-related biomarkers, including clinical, biophysical, molecular, cellular, and imaging markers as well as patient-reported outcomes
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 50
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebos Sodiumchloride 0,9% solution for injection, subcutaneous injection, administered on day 0, 28 and 84. Guselkumab Guselkumab Guselkumab 100 mg/ml in prefilled syringe, subcutaneous injection, administered on day 0, 28 and 84.
- Primary Outcome Measures
Name Time Method Erythema measurement of the skin from day -14 to day 168 Redness of the skin will be determined using a colorimeter
Multispectral imaging from day -14 to day 168 The redness and superficial morphology of (non-)lesional skin sites will be determined using a multispectral imaging system
Psoriasis Area and Severity Index (PASI) Assessment from day -14 to day 168 Psoriasis Area and Severity Index (PASI) combines the assessment of the severity of lesions and the area affected into a single score in the range 0 (no disease) to 72 (maximal disease).
Activity Tracking Heartrate from day -14 to day 168 Subjects are requested to wear a smartwatch at all times which heart rate (beats per minute)
Blister immune cell subsets from day 0 to day 112 Blisters will be induced on the non-lesional skin and the blister exudate aspirated. Blister exudate will be analyzed for the presence of immune cells (e.g. CD4+ and CD8+ T-Cells) using flow cytometry
Physicians Global Assesment (PGA) Assessment from day -14 to day 168 Physicians Global Assesment (PGA) is a 4-point scale ranging from 0 (no disease) to 4 (maximal disease).
Percentage body surface affected (%BSA) Assessment from day -14 to day 168 Percentage body surface affected (%BSA) is the area of lesional skin as a percentage of the total body surface
Laser Speckle Contrast imaging from day -14 to day 168 The cutaneous microcirculation of (non-)lesional skin sites will be monitored over a 30 second timespan with a laser speckle contrast imager
Patient reported outcomes from day -14 to day 168 Patients will be asked to report on their condition through an NRS scale (0 (better)- 10 (worse)) for sleeplessness, itch and quality of life. Additionally, patients image their lesions on a daily basis using a mobile device.
Cutaneous microbiome from day -14 to day 112 The microbiome is collected by swabbing. The abundance of bacteria is thereafter determined using next-generation sequencing.
Fecal microbiome from day 0 to day 112 The bacterial composition of stool samples is determined using next-generation sequencing.
digital PASI from day -14 to day 168 Digital Psoriasis Area and Severity Index (dPASI) calculated from standardized total body photography
Thermography from day -14 to day 168 Body surface temperature of (non-)lesional skin will be determined using a thermal imaging infrared camera
Activity Tracking Steps from day -14 to day 168 Subjects are requested to wear a smartwatch at all times which register steps (amount of steps taken)
Anti-drug antibodies from day 0 to day 168 The occurrence of antibodies directed against guselkumab will be monitored during the treatment period (ng/ml)
Skin surface biomarkers from day -14 to day 112 Superficial protein biomarkers are samples using a FibroTx Patch. Afterwards, these patches are extracted and the presence of protein biomarkers (e.g. HBD-3) determined using ELISA.
Skin barrier function from day -14 to day 168 The trans epidermal water loss of (non-)lesional skin will be determined as function of the inside-out barrier function of the skin. (g/m2/h)
Transcriptome of biopsies day 0 to day 112 Biopsies will be analyzed with an untargeted next-generation sequencing approach.
Activity Tracking Sleep from day -14 to day 168 Subjects are requested to wear a smartwatch at all times which register sleep (hrs, minutes, seconds of rest)
Cells/ml; Circulating immune cell subsets from day -14 to day 168 Blood be drawn during using a venipuncture during visits and analyzed for the presence of immune cells (e.g. CD4+ and CD8+ T-Cells) using flow cytometry
Circulating protein biomarkers from day -14 to day 168 Blood be drawn during using a venipuncture during visits and analyzed for the presence of various chemokines and cytokines (e.g. CCL20, CCL17, CXCL8)
Blister protein biomarkers from day 0 to day 112 Blisters will be induced on the non-lesional skin and blister fluid aspirated. Blister fluid will be analyzed for the presence of various chemokines and cytokines (e.g. CCL20, CCL17, CXCL8) (ng/ml)
Immunohistochemistry of biopsies day 0 to day 112 Biopsies will be sectioned and stained for the determination of the epidermal homeostasis (proliferation, differentiation and thickness) and infiltration of cellular immune subsets (e.g. presence of CD4 and CD8).
Lipidomics of the stratum corneum from day -14 to day 112 Tape stripping will be performed on (non-)lesional skin and lipids are subsequently extracted from the tape and analyzed using Liquid Chromatogrpahy-Mass Spectormetry. (ng/cm2)
Patient genotyping day -14 A whole blood sample will be used to scan for common mutations in genes implicated in psoriasis using next-generation sequencing.
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (1)
Centre for Human Drug Research
🇳🇱Leiden, Netherlands