Clinical trial NCT03327116: Effect of Methotrexate on Inflammatory Response in Adult Atopic Dermatitis Patients
Official title: Evaluation of the Effect of Methotrexate on Cytokines and Chemokines Involved in the Inflammatory Response in Adult Patients With Atopic Dermatitis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Atopic Dermatitis
Keywords: atopic dermatitis
pruritus
methotrexate
inflamation
IL-31
Lead sponsor: University of Sao Paulo General Hospital
Sponsor class: OTHER
Collaborators: name: FUNADERSP (Foundation for Research Support of the State of São Paulo)
First posted: 2017-10-31
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

Brief summary: Atopic dermatitis (AD) is a chronic inflammatory skin disease associated with pruritus. Methotrexate can be used to treat refractory disease to conventional therapy.

It will be conducted a single arm trial with twelve adult patients with moderate to severe AD on methotrexate for 24 weeks.

Investigators intend to evaluate the effect methotrexate on cytokines and chemokines involved in the inflammatory response, on IgE levels, on pruritus, and on EASI and SCORAD severity scores.

Detailed description: Introduction: Atopic dermatitis (AD) is a chronic inflammatory skin disease associated with pruritus. Methotrexate (MTX) can be used to treat refractory disease to conventional therapy, but there are few studies showing its effect on the profile of cytokines involved in the inflammatory response.

Objectives: To assess the effect of MTX on the cytokines involved in the inflammatory response of adult AD patients treated with methotrexate for 24 weeks. As specific objectives, investigators intend to assess the evolution of serum IgE levels, the EASI (Eczema Area and Severity Index) and SCORAD (Scoring Atopic Dermatitis) severity scores and pruritus in them.

Methods: It will be conducted an open, prospective study with twelve adult patients with moderate to severe AD on MTX for 24 weeks. Each participant is expected to attend 7 visits during 6 months of follow-up. In clinical healthy and injured skin, two assessments will be performed: 1) mRNA expression of IL-4, IL-10, IL-17A, IL-22, IL-31, oncostatin M receptor (OSMR), alpha subunit IL-31 (IL-31RA) receptor, TNF-α, IFN-γ, TSLP, TARC and MDC by Real Time-PCR at the initial week and week 24; 2) expression of IL-31, IL-31RA, OSMR, TSLP and Ki67 by immunohistochemistry at the initial week and week 24.

Skin samples from non-atopic subjects will be utilized as controls for the assays, paired by gender and age.

Additional analysis of serum levels of IgE (nephelometric method) at the initial week and week 24 of the study will be performed.

AD severity scores (EASI and SCORAD) will be tested and pruritus will be analyzed by a visual analog scale at the initial, week 12 and week 24.

Eligibility criteria: Inclusion Criteria:

* AD (Hanifin and Rajka criteria) moderate to severe (EASI ≥ 7.1 and SCORAD ≥ 25);
* Age ≥ 18 years;
* Women without the potential to become pregnant or using an effective method of contraception and with a negative pregnancy blood test;
* Men without a desire of pregnancy and who use condom in sexual intercourse.

Exclusion Criteria:

* Hepatic and / or renal insufficiency;
* Anemia, thrombocytopenia and / or leukopenia;
* Use of concomitant hepatotoxic drug;
* Active infection;
* Allergy to MTX;
* Excessive alcohol intake;
* Difficulty to understand how to take methotrexate;
* HIV infection or other immunosuppression condition;
* Therapy with UVA or UVB, corticoid, cyclosporine, immunobiological, azathioprine within 12 weeks prior to introduction of methotrexate.

Primary outcomes:
measure: Change from baseline of cytokines and chemokines expression at 24 weeks
timeFrame: week 24
Secondary outcomes:
measure: Change from baseline of IgE level at 24 weeks
timeFrame: week 24
measure: Change from baseline of Pruritus at 12 weeks
timeFrame: week 12
measure: Change from baseline of Pruritus at 24 weeks
timeFrame: week 24
measure: Change from baseline of SCORAD severity score at 12 weeks
timeFrame: week 12
measure: Change from baseline of SCORAD severity score at 24 weeks
timeFrame: week 24
measure: Change from baseline of EASI severity score at 12 weeks
timeFrame: week 12
measure: Change from baseline of EASI severity score at 24 weeks
timeFrame: week 24
Other outcomes:
Locations:
city: São Paulo
country: Brazil
facility: Hospital das Clínicas of the University of São Paulo Medical School, Department of Dermatology
state: SP
Study officials:
References: