Clinical Trial Details
— Status: Recruiting
Administrative data
NCT number |
NCT04750161 |
Other study ID # |
CRFSJ0133 |
Secondary ID |
|
Status |
Recruiting |
Phase |
|
First received |
|
Last updated |
|
Start date |
March 2, 2021 |
Est. completion date |
June 2021 |
Study information
Verified date |
March 2021 |
Source |
St. James's Hospital, Ireland |
Contact |
Matthew Coalter, MB BCh BAO MSc |
Phone |
0858351212 |
Email |
coalterm[@]tcd.ie |
Is FDA regulated |
No |
Health authority |
|
Study type |
Observational
|
Clinical Trial Summary
Pro-inflammatory cytokines are critically important drivers of inflammatory and autoimmune
diseases and cytokine-targeted biologics have been transformative in the treatment of several
inflammatory and autoimmune diseases. As the diversity of approved cytokine-targeted biologic
therapies grows, it will become increasingly important to stratify patients on the basis of
specific genetic or disease biomarker phenotypes to ensure that patients receive the
appropriate cytokine-targeted biologic, at the appropriate dose, and at the appropriate time.
This project aims to explore patterns of pro-inflammatory cytokine/chemokine expression
within normal versus (i) psoriatic, (ii) eczematic, (iii) ichthyotic human skin, as well as
in human and mouse models of skin inflammation, with the objective of identifying cytokine
response profiles ('cytokine fingerprints') that will provide a molecular basis for (a) the
stratification of patients into disease subtypes that (b) enable cytokine-directed biologics
to be targeted towards patients that are most likely to benefit from them. The investigators
anticipate that 'cytokine fingerprinting' will aid in the selection of the most appropriate
biologics in patients that are most likely to benefit from such therapies.
Description:
Neutrophils, the 'first responder' cells of the immune system are recruited rapidly to sites
of infection or inflammation. Neutrophil granule proteases, cathepsin G, elastase and
proteinase-3, are thought to function as anti-microbial effectors, cooperatively working to
kill microorganisms during infection. However, evidence also suggests that these enzymes play
an important role in the coordination and escalation of inflammatory reactions, but how this
is achieved has remained obscure. IL-1 family cytokines are important initiators of
inflammation but require processing by enzymes for activation. The IL-1 cytokine family is
made up of 11 members, but this study will focus on the processing and activation of 7 of
these pro-inflammatory cytokines (IL-1a, IL-1b, IL-18, IL-33, IL-36a, IL-36b and IL-36g).
Members of the extended IL-1 family are found at high levels in barrier surfaces such as the
skin, and thought to play a role in conditions such as psoriasis, atopic dermatitis/eczema
and ichthyosis. Psoriasis particularly is associated with massive neutrophil influx. This
study aims to investigate the physiological relevance of neutrophil proteases in the
activation of IL-1 family cytokines in skin disorders.
The investigators plan to study the contribution of neutrophil proteases to inflammation in
normal skin versus lesions from areas of skin affected by the conditions described above. The
investigators are interested in measuring the levels of active neutrophil proteases in normal
healthy skin versus skin lesions from affected sites compared to non-lesional, unaffected
skin. The investigators also are interested to see if levels of neutrophil proteases found in
lesions from affected skin sites are able to process and activate IL-1 family cytokines and
contribute to inflammation in this way.
The investigators plan to include up to 80 participants; 20 healthy volunteers, 20
participants who will have a diagnosis of psoriasis, 20 participants who have a diagnosis of
atopic dermatitis and 20 patients who have a diagnosis of ichthyosis with active lesions on
their arms. Skin samples from normal versus lesional and non-lesional, unaffected skin will
be taken by tape stripping method.