Ignite Creation Date:
2024-05-19 @ 5:34 PM
Last Modification Date:
2024-10-26 @ 3:29 PM
Study NCT ID:
NCT06411106
Status:
RECRUITING
Last Update Posted:
2024-05-13
First Post:
2024-05-08
Brief Title:
Deep Phenotyping of Cutaneous Lupus Erythematosus
Sponsor:
Centre for Human Drug Research Netherlands
Organization:
Centre for Human Drug Research Netherlands
Study Overview
Official Title:
An Exploratory Single-center Two-part Study to Characterize Cutaneous Lupus Erythematosus and Investigate the Effect of an Immune Challenge by Comparing CLE Patients With Healthy Volunteers
Status:
RECRUITING
Status Verified Date:
2024-05
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Cutaneous lupus erythematosus CLE is an autoimmune disease of which the pathogenesis and pathophysiology are not fully understood Given the complex and heterogeneous character of the disease identification and development of specific biomarkers for diagnosis disease subtyping disease severity and treatment response in CLE is challenging Therefore the main objective of the current study is to further characterize CLE by using a deep phenotyping approach Moreover the role of TLR7 activation in the pathophysiology of the various clinical subtypes of CLE will be specifically studied With this approach the investigators aim to characterize objectively measured disease characteristics and detect novel biomarkers for CLE-subtypes
Detailed Description:
Cutaneous lupus erythematosus CLE is a rare but burdensome autoimmune disease that includes various subtypes including acute cutaneous LE ACLE subacute cutaneous LE SCLE intermittent cutaneous LE ICLE ie lupus tumidus LET and chronic cutaneous LE CCLE These subtypes differ in lesion morphology and histopathology however disease stratification is often a challenge
Knowledge on mechanisms involved in the pathogenesis and pathophysiology of CLE is growing however much remains unknown The current concept regarding the onset of the disease comprises a genetic background predisposing to CLE triggered by factors such as UV light what leads to cellular stress and eventually to the release of DNA components in keratinocytes Fetter et al 2022 Activation of both Toll-like receptor TLR-dependent and TLR-independent inflammatory signalling cascades leads to increased expression of several cytokines in particular type I interferon IFN Type I interferon mediates increased expression of proinflammatory chemokines via the JAK-STAT pathway leading to recruitment of immune cells release of cytokines and a chronic reactivation of innate immune pathways
Findings on the pathogenesis of the disease have led to the development of several targeted therapies that are currently being investigated in clinical trials However blockage of one important pathway might not suffice for decreasing disease activity given the limited efficacy of selective IFN antibodies in clinical trials Kalunian et al 2016 Khamashta et al 2016 Werth et al 2017
Only few biomarkers for CLE have been validated and widely incorporated into clinical practice Zhu et al 2021 Type I interferon-inducible proteins can be potentially used to assess disease severity of SCLE and CDLE Braunstein et al 2013 Furthermore low complement in CLE patients may be related to poor prognosis and increased risk of developing systemic disease Vera et al 2010 Vera et al 2010
Therefore the objectives of the current study are to evaluate disease-related characteristics in CLE patients and to evaluate the variability between patients using a deep phenotyping approach and to investigate the immune response of CLE patients following an ex vivo and in vivo imiquimod skin challenge The study consists of an observational part A and interventional part B part in CLE patients and healthy volunteers- With this approach the investigators aim to characterize objectively measured disease characteristics and detect novel biomarkers for CLE-subtypes
This study is part of the Next Generation Immuno Dermatology consortium SKINERGY trials
Knowledge on mechanisms involved in the pathogenesis and pathophysiology of CLE is growing however much remains unknown The current concept regarding the onset of the disease comprises a genetic background predisposing to CLE triggered by factors such as UV light what leads to cellular stress and eventually to the release of DNA components in keratinocytes Fetter et al 2022 Activation of both Toll-like receptor TLR-dependent and TLR-independent inflammatory signalling cascades leads to increased expression of several cytokines in particular type I interferon IFN Type I interferon mediates increased expression of proinflammatory chemokines via the JAK-STAT pathway leading to recruitment of immune cells release of cytokines and a chronic reactivation of innate immune pathways
Findings on the pathogenesis of the disease have led to the development of several targeted therapies that are currently being investigated in clinical trials However blockage of one important pathway might not suffice for decreasing disease activity given the limited efficacy of selective IFN antibodies in clinical trials Kalunian et al 2016 Khamashta et al 2016 Werth et al 2017
Only few biomarkers for CLE have been validated and widely incorporated into clinical practice Zhu et al 2021 Type I interferon-inducible proteins can be potentially used to assess disease severity of SCLE and CDLE Braunstein et al 2013 Furthermore low complement in CLE patients may be related to poor prognosis and increased risk of developing systemic disease Vera et al 2010 Vera et al 2010
Therefore the objectives of the current study are to evaluate disease-related characteristics in CLE patients and to evaluate the variability between patients using a deep phenotyping approach and to investigate the immune response of CLE patients following an ex vivo and in vivo imiquimod skin challenge The study consists of an observational part A and interventional part B part in CLE patients and healthy volunteers- With this approach the investigators aim to characterize objectively measured disease characteristics and detect novel biomarkers for CLE-subtypes
This study is part of the Next Generation Immuno Dermatology consortium SKINERGY trials
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| NL8464505623 | OTHER | CCMO | None |