Effect of Sublingual Immunotherapy With Mite Extract in Patients With Atopic Dermatits: Placebo-controlled Double-blind Randomized Study
Trial Snapshot
- Phase
- Phase 4
- Status
- Completed
- Enrollment
- 91
- Locations
- 1
- Primary Endpoint
- Decrease in Severity Scoring of Atopic Dermatitis (SCORAD)
Study Overview
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
- st week 1 drop 2 drops 4 drops
- nd week 6 drops 8 drops 8 drops
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Triple (Participant, Care Provider, Investigator)
Masking Description
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) and severity (SCORAD less than 50 and greater / equal 50)**, 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.
** Initial SCORAD was not part of the stratification because it was part of the primary outcome variable.
Eligibility Criteria
- Ages
- 3 Years to — (Child, Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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;
Arms & Interventions
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
- st week 1 drop 2 drops 4 drops
- 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
Intervention: Mite extract sublingual immunotherapy (SLIT) (Drug)
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
- st week 1 drop 2 drops 4 drops
- nd week 6 drops 8 drops 8 drops
Intervention: Placebo - Immunotherapy allergen diluent
Intervention: Placebo (Other)
Outcomes
Primary Outcomes
Decrease in Severity Scoring of Atopic Dermatitis (SCORAD)
Time Frame: Measures at baseline and after 18 months
The SCORAD is calculated using the extent of the injury, intensity and subjective symptoms, the formula used for the calculation is A / 5 + 7B / 2 + C (A - extent B - intensity C-subjective symptoms). The extent can vary from zero to 100, applying the nine rule also used in large burned patients. The intensity varies from zero to 18, divided into six items, including erythema, edema, excoriation, lichenification, and dryness. Subjective symptoms range from zero to 30 evaluated by means of analog pruritus scale and sleep. The SCORAD severity rating is: 0-20 mild 20-40 moderate \> 40 severe Based on our clinical experience, it was decided to consider as the main outcome a 15-point decrease in SCORAD,in any degree of severity, in 40% of subjects in the treatment group and 15% in the placebo group.
Secondary Outcomes
- Analog Visual Scale of Symptoms(3, 6, 9, 12,15 and 18 months)
- IgG4 antibodies to mite allergens Der p 1, Der p 2 and Der p 10(0 and 18 months)
- Specific IgE antibodies to purified allergens and to Staphylococcal allerg(0 and 18 months)
- Type 2 and regulatory cytokines(0, 9 and 18 months)
- EASI (Eczema Area and Severity Index)(3, 6, 9, 12, 15 and 18 months)
- IGA (Investigator Global Assessment)(3,6,9,12,15 and 18 months)
- DLQI (Dermatology Life Quality Index)(3, 6, 9, 12,15 and 18 months)
- Pruritus scale(3, 6, 9, 12, 15 and 18 months)
Investigators
Fabio Carmona
Head of Medical School of Ribeirão Preto - University of São Paulo Children´s Hospital
Casa Espirita Terra de Ismael