Deep Phenotyping of Cutaneous Lupus Erythematosus

NCT06411106 | Recruiting

• 2 other identifiers: CHDR2307NL84645.056.23
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

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).

Conditions

Cutaneous Lupus Erythematosus

Keywords

CLE; Cutaneous lupus erythematosus; Deep phenotyping; Immune challenge; Healthy volunteers

Outcome Measures

Primary Outcomes (12)

• Skin punch biopsies

  Skin punch biopsies (4mm) will be taken from (non-)lesional skin and healthy for histology and RNA-sequencing analysis.

  Day 15

• 3D Multispectral imaging

  The redness and superficial morphology of (non-)lesional skin sites and healthy skin will be determined using a 3D multispectral imaging system.

  Day 1 - 15

• Laser Speckle Contrast Imaging (LSCI)

  The cutaneous microcirculation of (non-)lesional skin sites and healthy skin will be monitored over a 40 second timespan with a laser speckle contrast imager.

  Day 1 - 15

• Line-Field Confocal Optical Coherence Tomography (LC-OCT)

  LC-OCT is a non-invasive optical imaging technique based on a combination of the optical principles of optical coherence tomography and reflectance confocal microscopy with line-field illumination, which can generate cell-resolved images of the skin, in vivo, in vertical section, horizontal section and in three dimensions.

  Day 1 - 15

• Skin barrier function by Trans-Epidermal Water Loss (TEWL)

  The barrier status by trans epidermal water loss of (non-)lesional skin and healthy skin will be determined using TEWL.

  Day 1 - 15

• Cutaneous microbiome

  The cutaneous microbiome of (non-)lesional skin and healthy skin is collected by swabbing.

  Day 15

• Lipidomics of the stratum corneum and OLINK

  Tape stripping will be performed on (non-)lesional skin and healthy skin for extraction of lipids for analysis and analysis will be performed using OLINK.

  Day 15

• Blister immune cell subsets

  Blisters will be induced on the (non-)lesional skin and healthy skin, and the blister fluid will be aspirated. The blister fluid will be analyzed for the presence of immune cells using flow cytometry.

  Day 15

• Faecal microbiome (optional for patients)

  The bacterial composition of a stool samples will be determined.

  Day 15

• Circulating cytokines

  Blood will be drawn using a venipuncture and analyzed for cytokines.

  Day 15

• Interferon (IFN) signature

  Blood will be drawn using a venipuncture and analyzed for gene expression related to interferon (IFN).

  Day 15

• User experience and subjective burden questionnaire

  Measures the user experience and subjective burden of the different assessments performed in this study.

  Day 15

Secondary Outcomes (3)

• Ex vivo response to imiquimod

  Day 15

• In vivo response to imiquimod

  Day 1 - 4 (Part B)

• Patient reported outcomes

  Day 1- 4 (Part B)

Study Arms (1)

Arm

EXPERIMENTAL

CDLE patients and healthy volunteers In part B of this study, 5 mg imiquimod (100 mg Aldara®) per skin area (in total two skin areas) will be applied for two consecutive days under occlusion.

Drug: IMIQUIMOD cream 50mg/g

Interventions

IMIQUIMOD cream 50mg/g DRUG

5 mg imiquimod (100mg Aldara®) per treatment site with a 12mm Finn chamber

Also known as: Aldara

Arm

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed informed consent prior to any study-mandated procedure.
• Male or female subjects, 18 to 65 years of age at the time of signing informed consent; in general, stable good health as per judgement of the investigator based upon the results of a medical history, physical examination, vital signs, ECG, and laboratory assessments performed at screening. Repeated laboratory testing may be performed at the discretion of the clinical investigator.
• Body mass index (BMI) \> 18.0 and \< 32.0 kg/m2
• Fitzpatrick skin type I-III (Caucasian).
• Subjects and their partners of childbearing potential must use effective contraception for the duration of the study.
• No clinically significant skin disease as judged by the investigator.
• No history of hypertrophic scarring or keloid.
• Subject is willing to refrain from application of any topical product (e.g., ointments, cream or washing lotions) on the target lesion(s)skin 24 hours prior to every study visit day.
• Subject has the ability to communicate well with the investigator in the Dutch language and is willing to comply with the study requirements.
• Signed informed consent prior to any study-mandated procedure.
• Male or female CLE patients, 18 to 65 years of age at the time of signing informed consent; in general, stable good health as per judgement of the investigator based upon the results of a medical history, physical examination, vital signs, ECG, and laboratory assessments performed at screening. Repeated laboratory testing may be performed at the discretion of the clinical investigators.
• Body mass index (BMI) \> 18.0 and \< 35.0 kg/m2.
• Only applicable for CDLE patients who will also participate in part B: Fitzpatrick skin type I-III (Caucasian).
• Subjects and their partners of childbearing potential must use effective contraception for the duration of the study.
• Patient has the ability to communicate well with the investigator in the Dutch language and is willing to comply with the study requirements.

You may not qualify if:

• (History of) immunological abnormality (e.g., immune suppression) that may interfere with study objectives, in the opinion of the investigator.
• Have any current and/or recurrent clinically significant skin condition, including tattoos.
• Antibiotic use, operation, or clinically significant intervention by surgeon/dentist within one month before Day 1.
• Positive hepatitis B surface antigen (HbsAg), hepatitis C antibody (HCV ab), or human immunodeficiency virus antibody (HIV ab) at screening.
• Participation in an investigational drug study within 3 months prior to screening or more than 4 times a year.
• Loss or donation of blood over 500mL within three months prior to screening.
• Subject is willing to refrain from the use of any medication within 28 days prior to Day 1, if the investigator judges it may interfere with the study objectives.
• History of alcohol abuse or consumption exceeding 5 standard drinks per day on average within 3 months of screening.
• Positive urine test for drugs or history of abuse at screening. Urine drug test may be repeated at the discretion of the investigator.
• Pregnant, a positive pregnancy test, intending to become pregnant during the study conduct, or breastfeeding.
• (A history of) any clinically significant medical condition, factor or abnormality that might interfere with study conduct or interpretation, as judged by the investigator.
• Previous use of Aldara (imiquimod cream) 3 months prior to the Day 1 visit in part B.
• Any active or chronic and/or uncontrolled condition that, in the opinion of the investigator, may influence study conduct or interpretation
• Presence of a relevant skin infection or disease in the target areas other than the observational disease (CLE), inclusively, but not limited to atopic dermatitis, psoriasis vulgaris and dermatomycosis.
• Having received treatments for CLE or any other disease within the following intervals prior to Day 1:

Sponsors & Collaborators

• Centre for Human Drug Research, Netherlands: lead

Study Sites (1)

Centre for Human Drug Research

Leiden, South Holland, 2333CL, Netherlands

RECRUITING

MeSH Terms

Conditions

Lupus Erythematosus, Cutaneous

Interventions

Imiquimod

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Skin Diseases

Intervention Hierarchy (Ancestors)

Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• R. Rissmann, RPh, PhD

  Centre for Human Drug Research

  PRINCIPAL INVESTIGATOR

Central Study Contacts

R. Rissmann, RPh, PhD

CONTACT

+31715246400; clintrials@chdr.nl

D. T. de Bruin, MD

CONTACT

+31715246400; clintrials@chdr.nl

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Part A of the study is observational and Part B has an intervention. In Part B, the intervention is a challenge with imiquimod. All patients and healthy volunteers will receive the same challenge.

Study Record Dates

• First Submitted: May 8, 2024
• First Posted: May 13, 2024
• Study Start: June 1, 2024
• Primary Completion: September 1, 2025
• Study Completion: September 1, 2025
• Last Updated: May 13, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)