Effect of Methotrexate on Inflammatory Response in Adult Atopic Dermatitis Patients

Atopic Dermatitis Clinical Trial

Official title:

Evaluation of the Effect of Methotrexate on Cytokines and Chemokines Involved in the Inflammatory Response in Adult Patients With Atopic Dermatitis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03327116
• Other study ID #: 13.368
• Status: Completed
• Phase: N/A
• Start date: November 1, 2017
• Est. completion date: December 1, 2018

Study information

• Verified date: December 2019
• Source: University of Sao Paulo General Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: December 1, 2018
• Est. primary completion date: July 1, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Atopic Dermatitis
• Dermatitis
• Dermatitis, Atopic
• Eczema

Intervention

Drug:
• Methotrexate
oral, 15 mg per week, 24 weeks

Locations

Country	Name	City	State
Brazil	Hospital das Clínicas of the University of São Paulo Medical School, Department of Dermatology	São Paulo	SP

Sponsors (2)

Lead Sponsor	Collaborator
University of Sao Paulo General Hospital	FUNADERSP (Foundation for Research Support of the State of São Paulo)

Country where clinical trial is conducted

Brazil, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from baseline of cytokines and chemokines expression at 24 weeks	mRNA expression of IL-4, IL-6, IL-10, IL-31, TSLP, INF-gamma, TNF-alpha, TARC and MDC by Real Time-PCR.; Immunohistochemistry with antibodies against IL-31, IL-31RA, OSMR, TSLP and Ki67	week 24
Secondary	Change from baseline of IgE level at 24 weeks	Nephelometric method	week 24
Secondary	Change from baseline of Pruritus at 12 weeks	Visual analogue scale (VAS). The VAS was used as a 10-cm long horizontal line with a starting point as "no itch" (0 points) and ending with "worst imaginable itch".	week 12
Secondary	Change from baseline of Pruritus at 24 weeks	Visual analogue scale (VAS). The VAS was used as a 10-cm long horizontal line with a starting point as "no itch" (0 points) and ending with "worst imaginable itch".	week 24
Secondary	Change from baseline of SCORAD severity score at 12 weeks	The SCORAD (Scoring atopic dermatitis) is a severity score used for atopic dermatitis.; To measure the extent of AD, the rule of nines is applied on a front/back drawing of the patient's inflammatory lesions. The extent can be graded from 0 to 100.; The intensity part of the SCORAD consists of 6 items: erythema, oedema/papulation, excoriations, lichenification, oozing/crusts and dryness. Each item can be graded on a scale from 0 to 3.; The subjective items include daily pruritus and sleeplessness. The SCORAD Index formula is: A/5 + 7B/2 + C. In this formula, A is defined as the extent (0-100), B is defined as the intensity (0-18) and C is defined as the subjective symptoms (0-20). The minimal score of SCORAD is 0 and the maximal score is 103 (most severe).	week 12
Secondary	Change from baseline of SCORAD severity score at 24 weeks	The SCORAD (Scoring atopic dermatitis) is a severity score used for atopic dermatitis.; To measure the extent of AD, the rule of nines is applied on a front/back drawing of the patient's inflammatory lesions. The extent can be graded from 0 to 100.; The intensity part of the SCORAD consists of 6 items: erythema, oedema/papulation, excoriations, lichenification, oozing/crusts and dryness. Each item can be graded on a scale from 0 to 3.; The subjective items include daily pruritus and sleeplessness. The SCORAD Index formula is: A/5 + 7B/2 + C. In this formula, A is defined as the extent (0-100), B is defined as the intensity (0-18) and C is defined as the subjective symptoms (0-20). The minimal score of SCORAD is 0 and the maximal score is 103 (most severe).	week 24
Secondary	Change from baseline of EASI severity score at 12 weeks	Eczema Area and Severity Index (EASI) is a tool for the measurement of severity of atopic dermatitis.; It ranges from 0 (no eczema) to 72 (most severe).; EASI is one of the core outcome instruments recommended to be included in all clinical trials on atopic dermatitis.	week 12
Secondary	Change from baseline of EASI severity score at 24 weeks	Eczema Area and Severity Index (EASI) is a tool for the measurement of severity of atopic dermatitis.; It ranges from 0 (no eczema) to 72 (most severe).	week 24