Molecular Allergen Component Resolved Diagnosis to Decide Immunotherapy (CRD-AIT)

Molecular Allergen Based Diagnosis Impact on Clinical Efficacy of Aeroallergen Immunotherapy- a Pragmatic Randomized Clinical Trial

Allergen immunotherapy (AIT) is used for the control of allergic diseases that are not completely responsive to avoidance strategies and/or pharmacotherapy. It is also considered the main treatment with the potential to modify allergic disease evolution. It's efficacy and safety in allergic rhinitis and asthma is supported by large systematic reviews and is recommended as a cornerstone treatment option in allergic disease. Molecular based allergy diagnosis has greatly evolved and the knowledge of molecular allergen sensitization pattern has been used to better define the allergen extract composition of AIT. However, uncertainty remains if this strategy is related to an increase of efficacy. Regulation of allergen extracts for allergen immunotherapy are currently underway in Europe, but there is still lack of standardization of relevant allergens and important differences are seen between allergenic contents.

Therefore, we aim to evaluate, in a real-life setting, the impact of using molecular-based diagnosis versus standard diagnostic tools in the efficacy of aeroallergen immunotherapy, using a pragmatic randomized controlled trial design and also to address the impact of the discrepancy between individual aeroallergen sensitization profiles and the major allergen molecular content of aeroallergen immunotherapy.

Study Overview

• Status: Recruiting
• Conditions: Asthma; Rhinitis, Allergic
• Intervention / Treatment: Diagnostic test: Standard diagnosis; Diagnostic test: Component resolved diagnosis

• Study Type: Interventional
• Enrollment (Anticipated): 210
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Diana M Silva, PhD; Phone Number: 964021365; Email: dianapereirasilva@chsj.min-saude.pt

Study Locations

• Portugal
  • Porto, Portugal
    • Recruiting
    • Faculty of Medicine Porto University/Centro Hospitalar de São João
    • Contact: Diana Silva, PhD; Phone Number: 964021365
    • Principal Investigator: Diana Silva, PhD
    • Sub-Investigator: Maria João Vasconcelos
    • Sub-Investigator: Daniela Brandão
    • Sub-Investigator: Mariana Bragança
    • Sub-Investigator: Diogo Mota

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 years and older (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Individuals with medical indication for aeroallergen immunotherapy(AIT) for allergic rhinoconjunctivitis or asthma, accordingly to the AIT guidelines;
• Over 5 years of age;
• Evidence of IgE-sensitization (positive skin prick tests and / or serum specific-IgE)
• Patients have indication to AIT to house dust mites and/or grass pollen, association with other allergens is not an exclusion criteria

Exclusion Criteria:

• Previously performed allergen immunotherapy
• Need the use of molecular allergen diagnosis to decide treatment and diagnostic strategy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: DIAGNOSTIC
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Standard diagnosis; Patients followed in the allergy clinic with indication for allergen immunotherapy using only standard diagnosis.	Diagnostic test: Standard diagnosis; Physicians will only have access to standard diagnostic tools namely skin prick tests and sIgE sensitization (not molecular IgE) and clinical history.
EXPERIMENTAL: CRD diagnosis; Patients followed in the allergy clinic with indication for allergen immunotherapy decided with standard diagnostic tools and molecular based diagnosis.	Diagnostic test: Component resolved diagnosis; Physicians in this group will have access to allergen molecular component sensitization profile, using ImmunoCAP ISAC E112i and to all standard diagnostic tolls

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of combined symptom and medication score (CSMS) at 52 weeks	Differences, in the mean change at 52 weeks, of CSMS between groups that were treated with AIT in the component resolved diagnosis versus standard diagnosis groups. CSMS is the sum of the daily symptom score (dSS, score 0 to 3) plus daily medication score (dMS; score 0 to 6)	0 to 52 weeks
Change of combined symptom and medication score (CSMS) at 24 weeks	Difference, in the mean change at 24 weeks, of CSMS between groups were treated with AIT in the component resolved diagnosis versus standard diagnosis groups.	0 to 24 weeks
Change of rhinitis symptoms using visual analogue scale at 52 weeks	Difference between groups(control vs intervention) in the mean change at 52 weeks, in the psychometric response scale. This scale is used to assess rhinoconjunctivitis discomfort and its impacts on symptom severity and need of treatment.	0 to 52 weeks
Change of rhinitis symptoms using visual analogue scale at 24 weeks	Difference between groups(control vs intervention) in the mean change at 52 weeks, in the psychometric response scale. This scale is used to assess rhinoconjunctivitis discomfort and its impacts on symptom severity and need of treatment.	0 to 24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Control of Allergic Rhinitis and Asthma Test (CARAT) at 52 weeks	Differences between groups (control vs intervention) in the mean change at 52 weeks in the scores obtained on the self-administered Portuguese validated questionnaire that assess symptoms and control of both allergic rhinitis and asthma in the previous 4 weeks. The final score ranges from 0 to 30, with scores over 24 indicating good control of asthma and allergic rhinitis, a four-point changes will be considered the minimal important difference	0 to 52 weeks
Change in Control of Allergic Rhinitis and Asthma Test (CARAT) at 24 weeks	Differences between groups (control vs intervention) in the mean change at 24 weeks in the scores obtained on the self-administered Portuguese validated questionnaire that assess symptoms and control of both allergic rhinitis and asthma in the previous 4 weeks. The final score ranges from 0 to 30, with scores over 24 indicating good control of asthma and allergic rhinitis, a four-point changes will be considered the minimal important difference.	0 to 24 weeks
Change in Asthma Control Test (ACT) at 52 weeks	Differences between control and intervention group of change in the self-report questionnaire regarding asthma symtoms that includes 5 items assessing each of the following for the previous 4 weeks. ACT score ranges from 5 (poor control of asthma) to 25 (complete control of asthma)	0 to 52 weeks
Change in Asthma Control Test (ACT) at 24 weeks	Differences between control and intervention group of change in the self-report questionnaire regarding asthma symtoms that includes 5 items assessing each of the following for the previous 4 weeks. ACT score ranges from 5 (poor control of asthma) to 25 (complete control of asthma)	0 to 24 weeks
Change in quality of life related with rhinitis and asthma at 52 weeks	Difference between groups regarding self-administered version of Rhinoconjunctivitis Quality of Life Questionnaire which is validated in Portuguese for patients over 12 years at 52 weeks. A change greater than 0.5 will be considered a critically clinically significant difference	0 to 52 weeks
Change in quality of life related with rhinitis and asthma at 24 weeks	Differences between groups regarding the self-administered version of Rhinoconjunctivitis Quality of Life Questionnaire which is validated in Portuguese for patients over 12 years at 24 weeks. A change greater than 0.5 will be considered a critically clinically significant difference	0 to 24 weeks
Change in ESPIA score- patient reported opinion allergen immunotherapy at 52 weeks	Differences between intervention and control groups in the self-administered questionnaire with 16 questions distributed in 4 dimensions: perception of effectiveness, activities and environment, cost-benefit balance and general satisfaction at 52 weeks	0 to 52 weeks
Change in ESPIA score- patient reported opinion allergen immunotherapy at 24 weeks	Differences in the self-administered questionnaire with 16 questions distributed in 4 dimensions: perception of effectiveness, activities and environment, cost-benefit balance and general satisfaction at 24 weeks	0 to 24 weeks
Change in the cost impact between groups	Direct and indirect healthcare related costs will be assessed in each of the groups before and after treatment and compared	0 and 52 weeks

Collaborators and Investigators

• Sponsor: Universidade do Porto
• Collaborators: Sociedade Portuguesa de Alergologia e Imunologia Clinica
• Investigators: Principal Investigator: Diana Silva, Faculty of Medicine Porto University

Publications and helpful links

General Publications

• Roberts G, Pfaar O, Akdis CA, Ansotegui IJ, Durham SR, Gerth van Wijk R, Halken S, Larenas-Linnemann D, Pawankar R, Pitsios C, Sheikh A, Worm M, Arasi S, Calderon MA, Cingi C, Dhami S, Fauquert JL, Hamelmann E, Hellings P, Jacobsen L, Knol EF, Lin SY, Maggina P, Mosges R, Oude Elberink JNG, Pajno GB, Pastorello EA, Penagos M, Rotiroti G, Schmidt-Weber CB, Timmermans F, Tsilochristou O, Varga EM, Wilkinson JN, Williams A, Zhang L, Agache I, Angier E, Fernandez-Rivas M, Jutel M, Lau S, van Ree R, Ryan D, Sturm GJ, Muraro A. EAACI Guidelines on Allergen Immunotherapy: Allergic rhinoconjunctivitis. Allergy. 2018 Apr;73(4):765-798. doi: 10.1111/all.13317. Epub 2017 Oct 30.
• Matricardi PM, Dramburg S, Potapova E, Skevaki C, Renz H. Molecular diagnosis for allergen immunotherapy. J Allergy Clin Immunol. 2019 Mar;143(3):831-843. doi: 10.1016/j.jaci.2018.12.1021.
• Dhami S, Nurmatov U, Arasi S, Khan T, Asaria M, Zaman H, Agarwal A, Netuveli G, Roberts G, Pfaar O, Muraro A, Ansotegui IJ, Calderon M, Cingi C, Durham S, van Wijk RG, Halken S, Hamelmann E, Hellings P, Jacobsen L, Knol E, Larenas-Linnemann D, Lin S, Maggina P, Mosges R, Oude Elberink H, Pajno G, Panwankar R, Pastorello E, Penagos M, Pitsios C, Rotiroti G, Timmermans F, Tsilochristou O, Varga EM, Schmidt-Weber C, Wilkinson J, Williams A, Worm M, Zhang L, Sheikh A. Allergen immunotherapy for allergic rhinoconjunctivitis: A systematic review and meta-analysis. Allergy. 2017 Nov;72(11):1597-1631. doi: 10.1111/all.13201. Epub 2017 Jul 14.

Study record dates

Study Major Dates

• Study Start (ACTUAL): July 30, 2022
• Primary Completion (ANTICIPATED): September 30, 2023
• Study Completion (ANTICIPATED): December 30, 2023

Study Registration Dates

• First Submitted: April 21, 2022
• First Submitted That Met QC Criteria: July 1, 2022
• First Posted (ACTUAL): July 7, 2022

Study Record Updates

• Last Update Posted (ACTUAL): November 15, 2022
• Last Update Submitted That Met QC Criteria: November 14, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Immune System Diseases; Hypersensitivity, Immediate; Otorhinolaryngologic Diseases; Respiratory Hypersensitivity; Hypersensitivity; Nose Diseases; Rhinitis; Rhinitis, Allergic
• Other Study ID Numbers: 2017-21

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No