NCT06411106

Deep Phenotyping of Cutaneous Lupus Erythematosus

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
• Phase: N/A
• Study type: Interventional
• Enrollment: 40 (estimated)
• Sponsor: Centre for Human Drug Research, Netherlands · Academic / Other
• Sex: All
• Age: 18 Years – 65 Years
• Healthy volunteers: Accepted

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) i.e., 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.

Conditions

• Cutaneous Lupus Erythematosus

Interventions

Type	Name	Description
DRUG	IMIQUIMOD cream 50mg/g	5 mg imiquimod (100mg Aldara®) per treatment site with a 12mm Finn chamber

Timeline

• Start date: 2024-06-01
• Primary completion: 2025-09-01
• Completion: 2025-09-01
• First posted: 2024-05-13
• Last updated: 2024-05-13

Locations

1 site across 1 country: Netherlands