PGE2/IL-22 Pathway in Various Forms of Eczema
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|ClinicalTrials.gov Identifier: NCT04133506|
Recruitment Status : Not yet recruiting
First Posted : October 21, 2019
Last Update Posted : October 21, 2019
Objectives: Eczema is a chronic inflammatory skin condition characterised immunologically by T cellmediated inflammation. The pathogenic mechanisms involved in its development are incompletely understood and targeted treatment options are limited. The investigators will study the Prostaglandin E2 (PGE2)/IL22/IL17 pathway which plays an important role in murine model chronic skin inflammation. The investigators wish to identify subtypes of human eczema in which this pathway may be involved and to determine whether manipulation of this pathway may offer effective new treatments.
Design, tissue/cells, techniques and measurements: To address these objectives, the investigators will measure the expression of IL22, IL17A and PGE2 synthases and receptors in skin biopsies from eczema and psoriasis patients using immunohistochemistry (confirming this with RT-PCR). IL22/IL17 producing Tcells (from peripheral blood) and their skin-homing capability (by ex-vivo cell culture and flow cytometry) will be measured. Deriving immune cells from skin biopsies using Villanova's technique1, the investigators will determine the T-cell response to PGE2 looking at PGE2 receptors and cytokine expression, interrogating these cells by flow cytometry. To determine the sequence and kinetics of activation of the PGE2/IL22/IL17 pathway the investigators will measure each immune mediator at specific time points by recruiting healthy volunteers inducing irritant and allergic contact dermatitis using dithranol and DNCB respectively. The investigators will repeat the experiment dividing volunteers into two arms, one pre-treated for one week with a non-specific prostaglandin inhibitor (aspirin) and the second with a placebo control.
|Condition or disease||Intervention/treatment|
|Eczema||Drug: Aspirin 300mg|
|Study Type :||Observational|
|Estimated Enrollment :||60 participants|
|Official Title:||Defining a PGE2 Pathway in Regulating Eczema|
|Estimated Study Start Date :||November 2019|
|Estimated Primary Completion Date :||February 2022|
|Estimated Study Completion Date :||February 2022|
acute eczema patients with eczema <72 hours no drugs
chronic eczema with eczema > 72 hours no drugs
allergic contact dermatitis
allergic contact dermatitis with a clear allergen identified no drugs
patients with plaque psoriasis no drugs
dithranol or DNCB (used to induce irritant or allergic eczema used safely in similar research studies for decades) aspirin to half the group to assess the effects on downstream mediators
Drug: Aspirin 300mg
see earlier (only half of healthy volunteers receive aspirin)
- Laboratory assessment of skin and blood of patients [ Time Frame: 3 years ]We wish to determine if PGE2 and IL22 levels in skin and blood are elevated in specific subtypes of eczema by measuring this in their skin and blood when not receiving any treatments. This will take the form of measuring protein levels of PGE2 and IL-22 in blood and skin. This will allow us to stratify patients according to those in whom PGE2 and IL-22 is over-expressed (we don't expect this to be elevated in all patients) and will enable us to determine who we could treat in clinical trial in the future with future therapies.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04133506
|Contact: Fiona Cunningham, MB BCh||0131 242 6593 ext firstname.lastname@example.org|
|Contact: Richard Weller, MB BCh||0131 536 3229 ext 01315363229|
|Principal Investigator:||Richard Weller, MB BCh||NHS and University of Edinburgh|