The Role of Confocal Microscopy in Estimating Dupilumab Treatment Response for Moderate/Severe Atopic Dermatitis

NCT ID: NCT07098000

Last Updated: 2025-08-01

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Total Enrollment: 40 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2024-04-24
• Study Completion Date: 2026-04-12

Brief Summary

Atopic dermatitis (AD) is recognized as the most prevalent chronic inflammatory skin disease across all age groups. The introduction of reflectance confocal microscopy (RCM) signifies a substantial leap forward in the non-invasive skin assessment at a cellular level. This advancement holds the potential to diminish the need for skin biopsies in diagnosing and monitoring skin diseases. Given the variability in the efficacy of systemic treatments for AD among patients, RCM emerges as an attractive tool for real-time monitoring of treatment response. This capability enables the treating physician to customize treatment approaches accordingly. There exists a lack of data concerning the subsurface characteristics of the skin explored with RCM before, during, and after dupilumab treatment in patients with moderate to severe AD.

Hypothesis: The characteristics of AD skin at the cellular level evaluated by RCM correlate with treatment response with dupilumab Overall objectives: To evaluate the association between skin characteristics assessed by basal RCM and changes in EASI and vIGA-AD scores at 24 weeks in individuals with mod/sev AD treated with dupilumab.

Methods: Prospective cohort study. Forty patients with mod/sev AD starting dupilumab will be enrolled. Basal and periodic clinimetry, PROs, and evaluation of the affected skin through RCM will be done.

Expected results: To describe RCM phenotypes of responders and not responders to dupilumab Impact: Offering the medical community a non-invasive tool to improve phenotypic characterization for tailoring clinical decisions. The investigators strongly believe this could mark the initial stride towards adopting personalized medicine, ultimately resulting in enhanced therapeutic selection, dosage precision, optimized intervals, increased patient adherence, and reducing need for skin biopsies, particularly in infants.

Detailed Description

Study Design and Setting

This is a prospective cohort study conducted at Hospital Italiano de Buenos Aires, a high-complexity, non-profit institution with a longstanding commitment to patient care, medical education, and research. The Department of Dermatology spans over 17 clinical sites and is one of the largest in Argentina, with 155,000 annual consultations and a strong focus on immune-mediated skin disorders, including atopic dermatitis (AD). The Division of Immune Skin Diseases includes 12 board-certified dermatologists specialized in managing complex inflammatory skin conditions. Our department actively participates in the Atopic Dermatitis Quality of Care Initiative and collaborates with local and international networks such as the Argentine Society of Dermatology, Pediatric Dermatology Society, and Project ECHO® AD group.

Study Population and Recruitment Strategy

The study will enroll patients from the Buenos Aires Metropolitan Area (population ~14 million), where an estimated 3% of adults and 5% of children are affected by AD, with moderate-to-severe cases representing approximately 0.3%-0.5%. Dermatologists and allergists across all sectors-public, private, and social security-will be invited to refer eligible patients prior to dupilumab treatment initiation. Inclusion will not be restricted by insurance status or care setting, ensuring demographic and socioeconomic diversity.

Study Procedures

Patients will be referred to Hospital Italiano, where the study team will conduct consent and baseline evaluations. Study duration is up to 48 weeks, including four visits: baseline, week 12 and week 24. Systemic treatment will be prescribed independently by the referring physician, allowing the study to observe real-world therapeutic strategies. The coordinating center will manage clinimetric assessments, patient-reported outcomes (PROs), and imaging.

Baseline Assessments:

Demographics and medical history. Clinimetry: vIGA-AD, EASI, BSA, SCORAD, PGIS, PGIC. PROs: PP-NRS, SP-NRS, Sleep-NRS, POEM, ADCT, DLQI. Documentation of prescribed treatment: molecule, route, dose, schedule. RCM imaging of selected lesions (trunk, limbs, face), excluding hyperkeratotic or eroded acral lesions.

RCM Imaging Protocol:

Equipment: Vivascope 1500 and 3000 (Caliber ID). Mosaic acquisition (5x5 mm) at four skin depths: stratum corneum, stratum spinosum, dermoepidermal junction, and superficial dermis.

Stacked images collected from the corneal layer to ~250 μm depth. Facial lesions will be imaged with the handheld Vivascope 3000 when needed. Images stored in a secured, structured database.

Follow-Up Visits (Weeks 12 and 24):

Repeat clinimetry and PRO assessments. Treatment adherence and adverse event monitoring. Repeat RCM imaging on the same anatomical sites.

Predictive and Descriptive Variables:

RCM features: parakeratosis, hyperkeratosis, spongiosis, vesicles, acanthosis, exocytosis, non-edged dermal papillae, DEJ morphology, vascular dilation, dermal infiltration, melanophages.

Clinical: phenotype (e.g., classical, nummular, generalized lichenoid), comorbidities, prior therapies, IgE levels, family history.

Sample Size and Sampling Strategy

This exploratory study does not have a formal sample size estimation. The investigators expect to include 40 consecutive patients on dupilumab therapy, at least ten patients with the main phenotypes:

1. Classical: Lichenified/exudative flexural dermatitis, almost always associated with head-and-neck eczema and hand eczema

2. Generalized eczema with a lichenoid pattern: lichenification, excoriations, crusts, and xerosis

3. Nummular eczema with round, inflamed sores.

Statistical Analysis

Descriptive statistics will include frequencies for categorical variables and medians with interquartile ranges for continuous variables.

Primary analysis: Linear regression using the change (Δ) in EASI and vIGA-AD from baseline to week 24 as outcomes; baseline RCM features as predictors.

Secondary analysis: Logistic regression for binary clinical responses (e.g., achieving EASI-75), reporting odds ratios (ORs) with 95% confidence intervals (CIs).

All analyses will be conducted using STATA v14.1.

Conditions

Atopic Dermatitis

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Dupilumab treated patients

Dupilumab treated patients

No interventions assigned to this group

Control

10 healthy controls, five males and five females

No interventions assigned to this group

Eligibility Criteria

Inclusion Criteria

• ≥6 months of age.
• Diagnosis of AD based on Hanifin and Rajka criteria.
• Moderate-to-severe AD defined by: EASI >16, BSA >10%, SCORAD >25, or vIGA-AD 3-4.
• Starting dupilumab for AD indicated and initiated by the attending physician.
• Signed informed consent or assent with guardian approval.
• In those with previous systemic treatment (jaki, oral steroids, methotrexate and phototherapy), a predefined wash-out time of 4 weeks must be guaranteed.

Exclusion Criteria

• Inability to comply with study procedures.
• Refusal to provide informed consent.

• Minimum Eligible Age: 6 Months
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Hospital Italiano de Buenos Aires

OTHER

Sponsor Role: lead

Responsible Party

LUIS DANIEL MAZZUOCCOLO

Head of Department of Dermatology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Luis D Mazzuoccolo, MD

Role: PRINCIPAL_INVESTIGATOR

Hospital Italiano de Buenos Aires

Locations

Hospital Italiano de Buenos Aires

Buenos Aires, , Argentina

Countries

Argentina

References

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Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

6955

Identifier Type: -

Identifier Source: org_study_id