Multi-omics in Severe Asthma From Olive Pollen Allergy

NCT07721376 | Active Not Recruiting

• 1 other identifier: FCO-DPT-2024-01
• Study Type: observational
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

Patients with severe olive pollen allergy exhibit characteristic sensitization profiles, marked by strong recognition of minor allergens like Ole e 7, and, more importantly, show poor clinical responses to pharmacological treatments and immunotherapy. Previous studies have revealed that these patients experience a permanent immunological dysfunction (notably, dysregulated effector T-cell function) leading to a systemic inflammatory state that persists beyond the pollen season. The hypothesis is that short-term treatment (6 months) with Dupilumab can stabilize and reverse the inflammatory state in patients with severe olive pollen allergy (Project PI22/01737), enabling them to transition to conventional allergen immunotherapy. This study aims to deepen our understanding of the mechanisms underlying this immunological stabilization through multi-omics profiling (metabolomics, proteomics, transcriptomics) to explain the resolution of inflammation. Specifically, the goal is to restore an effective regulatory T-cell response, allowing for allergen-specific immunotherapy, which can be administered for three years in routine clinical practice as the only treatment capable of altering the disease's progression. Since immunotherapy relies on functional regulatory T-cell responses, this approach could validate a therapeutic strategy for these patients that modifies the disease long-term, breaking the cycle of chronic inflammation. This would reduce dependency on costly biologic treatments and significantly improve the quality of life.

Conditions

Severe Asthma; Allergy and Asthma; Pollen; Allergy, Asthma

Keywords

Severe asthma; Dupilumab; olive pollen allergy; immunotherapy

Outcome Measures

Primary Outcomes (6)

• Targeted serum metabolomic profile

  A targeted serum metabolomic profile associated with allergic inflammation will be assessed using a validated targeted metabolomics platform to evaluate changes induced by allergen immunotherapy.

  Baseline T0 (March 2024) and annually during the 3-year allergen immunotherapy period T1 (October 2024), T2, and T3, with additional assessments at 1 and 2 years after treatment completion (T4 and T5).

• Serum proteomic profile

  Serum levels of proteins involved in allergic inflammation and immune regulation will be quantified to evaluate changes during allergen immunotherapy. Protein quantification will be performed using a validated proximity extension assay (PEA).

  Baseline (T0), T1 (October 2024), annually during the 3-year allergen immunotherapy (T2-T3), and 1 and 2 years after treatment completion (T4-T5).

• Transcriptomic profile

  Gene expression profiles associated with allergic inflammation and immune regulation will be assessed by RNA sequencing to evaluate changes during allergen immunotherapy.

  Baseline (T0), T1 (October 2024), annually during the 3-year allergen immunotherapy (T2-T3), and 1 and 2 years after treatment completion (T4-T5).

• Asthma Control Test (ACT) score

  Asthma control will be assessed using the validated Asthma Control Test (ACT). Changes in ACT score during allergen immunotherapy will be evaluated.

  Every 4 weeks during the first 6 months (T0), annually during each olive pollen season the 3-year immunotherapy period (T1-T3), and at 1 and 2 years post-treatment (T4-T5).

• Asthma symptom and medication score

  Asthma symptoms and rescue medication use will be assessed using the predefined study score during each olive pollen season.

  Every 2 weeks during olive pollen season at T0, annually during each olive pollen (5 assessments) season the 3-year immunotherapy period (T1-T3), and at 1 and 2 years post-treatment (T4-T5).

• Peripheral T-cell immunophenotype

  Peripheral effector and regulatory T-cell subsets will be quantified by multiparametric flow cytometry to evaluate immunological changes during allergen immunotherapy.

  Baseline (T0), T1 (October 2024), annually during the 3-year allergen immunotherapy (T2-T3), and 1 and 2 years after treatment completion (T4-T5).

Secondary Outcomes (7)

• Baseline demographic characteristics

  Baseline (T0)

• Body mass index (BMI)

  Baseline (T0) and annually at T1-T5.

• Asthma control according to GEMA

  Every 2 weeks during olive pollen season at T0, annually during each olive pollen (5 assessments) season the 3-year immunotherapy period (T1-T3), and at 1 and 2 years post-treatment (T4-T5).

• Asthma treatment step according to GEMA

  Every 2 weeks during olive pollen season at T0, annually during each olive pollen (5 assessments) season the 3-year immunotherapy period (T1-T3), and at 1 and 2 years post-treatment (T4-T5).

• Rhinoconjunctivitis symptom and medication score

  Every 2 weeks during olive pollen season at T0, annually during each olive pollen (5 assessments) season the 3-year immunotherapy period (T1-T3), and at 1 and 2 years post-treatment (T4-T5).

Study Arms (2)

Dupilumab Pre-treated

Severe Phenotype Olive Pollen Allergy Patients Treated with Conventional Therapy plus Dupilumab

Conventional Treated

Severe Phenotype Olive Pollen Allergy Patients Treated with Conventional Therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

study with prospective follow-up medication , aimed at analyzing the inflammatory status of a group of asthmatic patients allergic to olive pollen with a severe phenotype during treatment with immunotherapy under routine clinical practice conditions and following the technical data sheet, in a group of patients who have previously received a short cycle of dupilumab and another group who have not received this treatment. The initiation and maintenance phase of immunotherapy is administered in our Immunotherapy Unit.

You may qualify if:

• Patients ≥ 18 years old, residing in areas with high olive pollen exposure (exceeding 10,000 grains/m³ during the past five pollen seasons).
• Proven allergy to olive pollen with predominant or isolated sensitization to Ole e 7.
• Diagnosis of asthma that remains uncontrolled despite completing steps 5-6 of the GEMA guidelines during the olive pollen season.
• Controlled asthma with a forced expiratory volume in 1 second (FEV1) \> 80% of the predicted normal value before starting subcutaneous immunotherapy (SCIT).

You may not qualify if:

• Having received allergen immunotherapy or biological treatment in the last 5 years.
• Pregnant women.
• Relevant comorbidity: cancer, myocardial infarction, severe immunological disorder .
• Contraindications contained in the official technical data sheet for Dupixent® (dupilumab).
• Contraindications of SCIT.

Sponsors & Collaborators

• Maimónides Biomedical Research Institute of Córdoba: lead
• CEU San Pablo University: collaborator

Study Sites (1)

Hospital Universitario Reina Sofia

Córdoba, Cordoba, 14004, Spain

Location

Related Publications (1)

• Escribese MM, Gomez-Casado C, Barber D, Diaz-Perales A. Immune Polarization in Allergic Patients: Role of the Innate Immune System. J Investig Allergol Clin Immunol. 2015;25(4):251-8.

  PMID: 26310039 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Blood

MeSH Terms

Conditions

Asthma; Hypersensitivity

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Immune System Diseases

Study Officials

• Berta Ruiz-Leon, MD., Ph.D.

  Hospital Universitario Reina Sofia de Cordoba

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 30, 2024
• First Posted: July 23, 2026
• Study Start: October 28, 2024
• Primary Completion (Estimated): November 30, 2029
• Study Completion (Estimated): November 30, 2029
• Last Updated: July 23, 2026

Record last verified: 2026-07

Locations

ES (1)