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Trial record 67 of 154 for:    Dermatitis, Atopic, 8

Effect of Sublingual Immunotherapy in Patients With Atopic Dermatitis

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03388866
Recruitment Status : Active, not recruiting
First Posted : January 3, 2018
Last Update Posted : January 17, 2019
Sponsor:
Collaborator:
Fundação de Amparo à Pesquisa do Estado de São Paulo
Information provided by (Responsible Party):
Fabio Carmona, Casa Espirita Terra de Ismael

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

Condition or disease Intervention/treatment Phase
Atopic Dermatitis Effects of Immunotherapy Drug: Mite extract sublingual immunotherapy (SLIT) Other: Placebo Phase 4

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) and severity (SCORAD less than 50 and greater / equal 50), performed by 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 selected during the SCORAD, of 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.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 91 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
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).

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 by 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.
Primary Purpose: Treatment
Official Title: Effect of Sublingual Immunotherapy With Mite Extract in Patients With Atopic Dermatits: Placebo-controlled Double-blind Randomized Study
Actual Study Start Date : May 2, 2018
Estimated Primary Completion Date : October 2019
Estimated Study Completion Date : May 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Eczema

Arm Intervention/treatment
Active Comparator: 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

Drug: Mite extract sublingual immunotherapy (SLIT)
Administration of increasing weekly doses of extracts of mites Dermatophagoides pteronyssinus in the treatment group.
Other Names:
  • Allergen specific sublingual immunotherapy
  • Sublingual immunotherapy (SLIT)

Placebo Comparator: 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

Other: 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).
Other Name: Diluent of the allergenic extract




Primary Outcome Measures :
  1. 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 Outcome Measures :
  1. EASI (Eczema Area and Severity Index) [ Time Frame: 3, 6, 9, 12, 15 and 18 months ]

    EASI is based on the extension and severity of Atopic Dermatitis. To obtain EASI, the proportion of body areas are taken into consideration, with head being equivalent to 10%, trunk 30%, upper extremities 20% and lower extremities 40%. The percentage of involvement of these four regions is determined using a scale of 0 to 6. Clinical signs including erythema, infiltration and/or papulation, excoriation, and lichenification are evaluated each on a scale of 0 to 3.

    Final score is calculated using the formula below. Severity is classified as: 0 = clear; 0.1 - 1.0 = almost clear; 1.1-7.0 = mild; 7.1-21.0 = moderate; 21.1-50.0 = severe; 50.1-72.0 = very severe. Any reduction in the EASI score will be accepted as a positive outcome.


  2. IGA (Investigator Global Assessment) [ Time Frame: 3,6,9,12,15 and 18 months ]

    IGA consists of evaluation of the severity of Atopic Dermatitis considering the inflammatory signs of the disease (erythema, papulation and infiltration). IGA is calculated according to the following scale: clear; almost clear; mild disease; moderate disease; severe disease; and very severe disease.

    Any reduction in the IGA score will be accepted as a positive outcome.


  3. DLQI (Dermatology Life Quality Index) [ Time Frame: 3, 6, 9, 12,15 and 18 months ]

    The DLQI is a questionnaire of 10 questions used to measure how much skin problems affect patient´s life in the past seven days.

    The scoring of each question is as follows:

    Very much, score of 3; A lot, score of 2; A little, score of 1; Not at all, score of 0; Not relevant, score of 0. Question 7, 'prevented work or studying', score of 3. The DLQI is calculated by summing the score for each question resulting in a maximum of 30 and a minimum of 0. The higher the score, the more quality of life is impaired.

    How to interpret meaning of DLQI scores:

    0 - 1 no effect at all on patient's life; 2 - 5 small effect on patient's life; 6 - 10 moderate effect on patient's life; 11 - 20 very large effect on patient's life; 21 - 30 extremely large effect on patient's life.

    The decrease of 4 or more points in DLQI is a secondary outcome measure.


  4. Analog Visual Scale of Symptoms [ Time Frame: 3, 6, 9, 12,15 and 18 months ]

    The analog visual scale consists of three questions that can be answered using a scale of 0 to 10, as described below:

    How much your skin itched last week? How much your skin peeled last week? How atopic dermatitis interfered with last week's sleep? Any reduction in the analog visual scale will be accepted as a positive outcome


  5. Pruritus scale [ Time Frame: 3, 6, 9, 12, 15 and 18 months ]

    Patients will provide information on their perception of pruritus in their daily life. The evaluation is subjective, varying from absence of pruritus to severe pruritus.

    Any reduction in the Pruritus scale will be accepted as a positive outcome


  6. IgG4 antibodies to mite allergens Der p 1, Der p 2 and Der p 10 [ Time Frame: 0 and 18 months ]
    It has been consistently shown that both subcutaneous and sublingual immunotherapy increase levels of specific IgG4 antibodies. Therefore, we expect to find an increase in levels of IgG4 to mite allergens at the end of treatment. IgG4 specific to Der p 1, Der p 2 and Der p 10 can be measured by ImmunoCAP.

  7. Specific IgE antibodies to purified allergens and to Staphylococcal allerg [ Time Frame: 0 and 18 months ]
    IgE antibodies to a panel of purified allergens will be assessed by ImmunoCAP and ImmunoCAP-ISAC, including Dermatophagoides pteronyssinus allergens rDer p1, rDer p 2 e rDer p 10. In addition, levels of specific IgE to Staphylococcal enterotoxins, including enterotoxins A, B, C and TSST, will be determined in patients' sera before and after treatment. It is expected that levels of IgE antibodies to mite allergens and to Staphylococcal enterotoxins will be decreased at the end of treatment

  8. Type 2 and regulatory cytokines [ Time Frame: 0, 9 and 18 months ]
    Reduction in type 2 cytokine group (IL4, IL5, IL9 and IL13) Regulatory cytokines [Time Frame: 0, 9 and 18 months] Increase of regulatory cytokines (IL-10 and TGF-beta)



Information from the National Library of Medicine

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Ages Eligible for Study:   3 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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;

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03388866


Locations
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Brazil
Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto
Ribeirão Preto, Sao Paulo, Brazil, 14048-900
Sponsors and Collaborators
Casa Espirita Terra de Ismael
Fundação de Amparo à Pesquisa do Estado de São Paulo
Investigators
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Study Director: Karla L Arruda, PhD Faculdade de Medicina de Ribeirão Preto

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Responsible Party: Fabio Carmona, Head of Medical School of Ribeirão Preto - University of São Paulo Children´s Hospital, Casa Espirita Terra de Ismael
ClinicalTrials.gov Identifier: NCT03388866     History of Changes
Other Study ID Numbers: SLIT_AD1
First Posted: January 3, 2018    Key Record Dates
Last Update Posted: January 17, 2019
Last Verified: January 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Fabio Carmona, Casa Espirita Terra de Ismael:
inhaled aeroallergens
eczema
pruritus
life quality
immunotheraphy
atopic dermatitis
Additional relevant MeSH terms:
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Dermatitis, Atopic
Dermatitis
Eczema
Skin Diseases
Skin Diseases, Genetic
Genetic Diseases, Inborn
Skin Diseases, Eczematous
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Immunologic Factors
Physiological Effects of Drugs