Clinical trial NCT03388866: Effect of Sublingual Immunotherapy in Patients With Atopic Dermatitis
Official title: Effect of Sublingual Immunotherapy With Mite Extract in Patients With Atopic Dermatits: Placebo-controlled Double-blind Randomized Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Atopic Dermatitis
Effects of Immunotherapy
Keywords: inhaled aeroallergens
eczema
pruritus
life quality
immunotheraphy
atopic dermatitis
Lead sponsor: Casa Espirita Terra de Ismael
Sponsor class: OTHER
Collaborators: name: Fundação de Amparo à Pesquisa do Estado de São Paulo
First posted: 2018-01-03
Enrollment: 91
Sex: ALL
Minimum age (years): 3
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model 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 / or immediate hypersensitivity skin tests, and mite allergen specific IgG4 (Der p 1 and Der p 2), before of the study.

Patients in the treatment group will undergo sublingual allergen-specific immunotherapy with weekly and weekly doses of extracts of Dermatophagoides pteronyssinus and Dermatophagoides farinae mites (60% and 40% respectively), according to the predetermined schedule. Patients in the control group will be submitted to the same administration schedule, but with allergen extract diluent (doubly distilled water solution and glycerin).
Primary purpose: TREATMENT

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.

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;

Primary outcomes:
measure: Decrease in Severity Scoring of Atopic Dermatitis (SCORAD)
timeFrame: Measures at baseline and after 18 months
Secondary outcomes:
measure: EASI (Eczema Area and Severity Index)
timeFrame: 3, 6, 9, 12, 15 and 18 months
measure: IGA (Investigator Global Assessment)
timeFrame: 3,6,9,12,15 and 18 months
measure: DLQI (Dermatology Life Quality Index)
timeFrame: 3, 6, 9, 12,15 and 18 months
measure: Analog Visual Scale of Symptoms
timeFrame: 3, 6, 9, 12,15 and 18 months
measure: Pruritus scale
timeFrame: 3, 6, 9, 12, 15 and 18 months
measure: IgG4 antibodies to mite allergens Der p 1, Der p 2 and Der p 10
timeFrame: 0 and 18 months
measure: Specific IgE antibodies to purified allergens and to Staphylococcal allerg
timeFrame: 0 and 18 months
measure: Type 2 and regulatory cytokines
timeFrame: 0, 9 and 18 months
Other outcomes:
Locations:
city: Ribeirão Preto
country: Brazil
facility: Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto
state: Sao Paulo
Study officials:
affiliation: Faculdade de Medicina de Ribeirão Preto
name: Karla L Arruda, PhD
role: STUDY_DIRECTOR
References: