Effect of Sublingual Immunotherapy in Patients With Atopic Dermatitis

NCT ID: NCT03388866

Last Updated: 2020-08-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 91 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-05-02
• Study Completion Date: 2020-06-26

Brief Summary

Atopic dermatitis (AD) is a chronic and recurrent inflammatory disease, prevalent between 1 and 20% in the world population, with a predominance of childhood, but which may be present in adult life. AD results from a complex interaction between genetic and environmental factors, with the presence of a defect in the skin barrier and deregulation of the immune response, culminating in an inflammatory response in the skin predominantly type 2. Disease control is based on restoring skin hydration, smoothing itching and controlling the process specific sensitizing agents such as inhalant allergens and foods that may pathogenesis of the disease. In selected patients who present IgE mediated response to inhalant allergens, allergen-specific immunotherapy can be effective. Classically, the subcutaneous route is the most used, however, sublingual immunotherapy (SLIT) has been used in increasing form. There are still few studies on the efficacy and safety of SLIT in atopic dermatitis. Therefore, the present study aims to to investigate the role of SLIT in the management of patients with AD allergic mites, through a randomized, double-blind and placebo-controlled study

Detailed Description

A total of 94 patients, 3 years of age or older, with clinical diagnosis of AD, without distinction of gender, ethnicity or social group, will be selected at HCFMRP-USP Allergy and Dermatology outpatient clinics. These patients will undergo clinical evaluation and laboratory tests, including blood count, total IgE, inhalant panel specific IgE, and immediate hypersensitivity skin tests, and mite allergen-specific IgG4 (Der p 1 and Der p 2), before of the study. To calculate the sample size, a response rate to the medication was defined as a 15 - point decrease in SCORAD (a score that includes lesion extent, intensity and subjective symptoms such as pruritus and sleep), which was determined through the experience of the service. It was estimated that 40% of the patients in the treatment group and 15% of the placebo group reached the proposed rate through a test with 80% power, and the need for 47 individuals in each group was defined.

Patients in the treatment group will undergo allergen-specific immunotherapy sublingually, with weekly doses of extracts of mites Dermatophagoides pteronyssinus and Dermatophagoides farinae (60% and 40% respectively), according to the scheme described in Tables 1 and 2. Patients in the control group will be submitted to the same administration schedule, but with the diluent of the allergenic extract (doubly distilled water solution and glycerin). Patients will be divided into groups according to randomization.

Subjects will be randomly divided into blocks of random size 4 or 6 and stratified according to age (less than 12 years and greater / equal 12 years), performed through the RedCap platform, available at FMRPUSP. This process will be performed by laboratory staff who will provide the extracts and the researchers will not have access to the lists of patients in each group. As for blinding, the bottles with extract and placebo will be provided by the already coded laboratory, and the team will only be responsible for the delivery and storage of the same.

Table 1 - Weekly dose schedule Monday Wednesday Friday

1. st week 1 drop 2 drops 4 drops

2. nd week 6 drops 8 drops 8 drops

Table 2 - Monthly Dilution Schedule Dilution of mite extract

1st and 2nd weeks (1st month) 1: 1000000 v: v 3rd and 4th weeks (1st month) 1: 100000 v: v

1st and 2nd weeks (2nd month)1: 10000 v: v 3rd and 4th weeks (2nd month) 1:1000 v: v

1st and 2nd weeks (3rd month) 1: 100 v:v 3rd and 4th weeks (3rd month) 1:10 v:v 3rd to 18th month 1:10 v: v

Individuals will be the outpatient clinics of the Allergy and Dermatology Service of the HCFMRP-USP. All medical records and clinical and dermatological examination will be recorded in medical records, as well as clinical evaluation by SCORAD , quality of life questionnaire and personal scale of symptoms, being evaluated at the beginning of treatment, after two, three, six, nine, twelve, fifteen and eighteen months of evolution.

Serum levels of IgG4 specific mite for Der p 1 and Der p 2 will be determined by ImmunoCAP and evaluated at the beginning and the end of treatment. Interleukins 4, 5, 9, 10 13, 17, TNFα, TGFβ and interferon-γ will be performed in plasma in the beginning, with 9 months of evolution and at the end of the study.

Conditions

Atopic Dermatitis; Effects of Immunotherapy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Mite extract sublingual immunotherapy

Use of mite extract sublingual immunotherapy (SLIT) with increasing weekly doses of extracts of mite Dermatophagoides pteronyssinus, as represented below:

Weekly dose schedule Monday Wednesday Friday

1. st week 1 drop 2 drops 4 drops

2. nd week 6 drops 8 drops 8 drops

Monthly Dilution Schedule Dilution of mite extract

1st and 2nd weeks (1st month) 1: 1000000 v: v 3rd and 4th weeks (1st month) 1: 100000 v: v

1st and 2nd weeks (2nd month)1: 10000 v: v 3rd and 4th weeks (2nd month) 1:1000 v: v

1st and 2nd weeks (3rd month) 1: 100 v:v 3rd and 4th weeks (3rd month) 1:10 v:v 3rd to 18th month 1:10 v: v

Group Type: ACTIVE_COMPARATOR

Mite extract sublingual immunotherapy (SLIT)

Intervention Type: DRUG

Administration of increasing weekly doses of extracts of mites Dermatophagoides pteronyssinus in the treatment group.

SLIT placebo

Patients in the control group will be submitted to the same administration schedule, but with allergen extract diluent (doubly distilled water solution and glycerin), as described below:

Weekly dose schedule Monday Wednesday Friday

1. st week 1 drop 2 drops 4 drops

2. nd week 6 drops 8 drops 8 drops

Intervention: Placebo - Immunotherapy allergen diluent

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

Placebo group will be submitted to administration of increasing weekly doses, but with diluent of the allergenic extract (doubly distilled water solution and glycerin).

Interventions

Mite extract sublingual immunotherapy (SLIT)

Administration of increasing weekly doses of extracts of mites Dermatophagoides pteronyssinus in the treatment group.

Intervention Type: DRUG

Placebo

Placebo group will be submitted to administration of increasing weekly doses, but with diluent of the allergenic extract (doubly distilled water solution and glycerin).

Intervention Type: OTHER

Other Intervention Names

Allergen specific sublingual immunotherapy; Sublingual immunotherapy (SLIT); Diluent of the allergenic extract

Eligibility Criteria

Inclusion Criteria

• Diagnosis of AD according to Hanifin and Rajka criteria;
• Age greater than or equal to 3 years;
• SCORAD equal to or greater than 15 points;
• Presence of skin tests and / or specific IgE positive for Dermatophagoides pteronyssinus and / or Dermatophagoides farinae;

Exclusion Criteria

• Pregnancy or breastfeeding;

• Minimum Eligible Age: 3 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Fundação de Amparo à Pesquisa do Estado de São Paulo

OTHER_GOV

Sponsor Role: collaborator

Casa Espirita Terra de Ismael

OTHER

Sponsor Role: lead

Responsible Party

Fabio Carmona

Head of Medical School of Ribeirão Preto - University of São Paulo Children´s Hospital

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Karla L Arruda, PhD

Role: STUDY_DIRECTOR

Faculdade de Medicina de Ribeirão Preto

Locations

Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto

Ribeirão Preto, São Paulo, Brazil

Countries

Brazil

Other Identifiers

SLIT_AD1

Identifier Type: -

Identifier Source: org_study_id