Clinical trial NCT04878770: NMF-CsA-Dupi Trial
Official title: Use of the NMF Biomarker as Predictive Diagnostic for Effective Use of Cyclosporine and Dupilumab in the Treatment of Atopic Dermatitis
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Dermatitis, Atopic
Keywords: natural moisturizing factor
systemic treatment
Lead sponsor: Erasmus Medical Center
Sponsor class: OTHER
Collaborators: name: ZonMw: The Netherlands Organisation for Health Research and Development
First posted: 2021-05-07
Enrollment: 318
Sex: ALL
Minimum age (years): 2
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This is a partially-blinded randomized controlled trial that investigates if NMF-biomarker status has an effect on the effectiveness of systemic treatment with CsA in children with moderate-to-severe AD. It also investigates whether stratification on the NMF biomarker results in an improvement of efficiency in the use of systemic treatment with CsA in the treatment of moderate-to-severe AD.
Primary purpose: TREATMENT

Brief summary: The goal of this study is to investigate whether stratification of children with atopic dermatitis on the NMF biomarkers results in an improvement of effectiveness and efficiency in the use of systemic treatment (ciclosporin and dupilumab) in moderate-to-severe atopic dermatitis.


Eligibility criteria: Inclusion Criteria:

* Children and adolescents, aged 2-18 years, with moderate-to-severe atopic dermatitis (diagnosed according to the UK working party criteria)
* Patient and parents/guardians able to participate in the study and willing to give written informed consent
* EASI (Eczema Area Severity Index) ≥ 6 at screening and baseline (corresponding with moderate-to-severe disease)
* IGA (Investigator Global Assessment) ≥ 3 at screening and baseline (corresponding with moderate-to-severe disease)

Exclusion Criteria:

* Children under the age of 2 years and patients older than 18 years
* Contraindication for ciclosporin
* Contraindication for dupilumab
* Patient (or one of the parents/guardians) not willing to be randomized
* Children with a history of any known primary immunodeficiency disorder
* Children with a history of cancer
* EASI \< 6 at screening or baseline
* IGA \< 3 at screening or baseline

Primary outcomes:
measure: EASI
timeFrame: t = 0, 1 month, 2 months, 3 months and 6 months
Secondary outcomes:
measure: EASI75
timeFrame: t = 1 month, 2 months, 3 months and 6 months
measure: IGA 0 or IGA 1
timeFrame: t = 0, 1 month, 2 months, 3 months and 6 months
measure: NRS-11 reduction for itch ≥ 4 points
timeFrame: t = 0, 1 month, 2 months, 3 months and 6 months
measure: POEM
timeFrame: t = 0, 1 month, 2 months, 3 months and 6 months
measure: SCORAD
timeFrame: t = 0, 1 month, 2 months, 3 months and 6 months
measure: RECAP
timeFrame: t = 0, 1 month, 2 months, 3 months and 6 months
Other outcomes:
measure: CDLQI ≥4 years
timeFrame: t = 0, 3 months and 6 months
measure: IDQoL <4 years
timeFrame: t = 0, 3 months and 6 months
measure: Emollients and steroid use in frequency and tubes used
timeFrame: t = 0, 1 month, 2 months, 3 months, 4 months, 5 months and 6 months
measure: Healthcare costs related to the treatment of AD
timeFrame: Over the course of 6 months
measure: Adverse events
timeFrame: Over the course of 6 months
measure: NMF measured via Raman spectroscopy
timeFrame: t = - 2 weeks, 0, 3 months and 6 months
measure: Microbiome profile
timeFrame: t = 0, 3 months and 6 months
measure: Humoral blood panel (systemic arms)
timeFrame: t = 0, 1 month, 3 months and 6 months
measure: Humoral blood panel (topical arm)
timeFrame: t = 0 and 6 months
measure: Cellular blood panel (systemic arm)
timeFrame: t = 0, 1 month, 3 months and 6 months
measure: FLG null mutations
timeFrame: t = 0
measure: Activity of atopy
timeFrame: t = 0, 3 months and 6 months
measure: Psychosocial factors (CBCL)
timeFrame: t = 0
measure: Psychosocial factors (OBVL)
timeFrame: t = 0
Locations:
city: Rotterdam
country: Netherlands
facility: Erasmus MC - Sophia Children's Hospital
state: Zuid-Holland
Study officials:
References: