ICS+LABA Vs. ICS+LABA+Omalizumab: Impact on Asthma Control and Gene Expression

NCT06869382 | Completed Phase 4 DMC

• 1 other identifier: IRB number 10-XD-154
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

Brief Summary

Asthma is a chronic respiratory disease characterized by airway inflammation and obstruction, leading to wheezing, breathlessness, chest tightness, and coughing. Uncontrolled asthma impairs daily activities and reduces quality of life, making it a significant global health concern affecting 334 million people worldwide. Proper management is essential to minimize its impact. The Global Initiative for Asthma (GINA) recommends inhaled corticosteroids (ICS) combined with long-acting beta-agonists (LABA) as a cornerstone therapy for moderate to severe asthma, reducing inflammation and providing sustained bronchodilation. This combination improves symptom control and prevents exacerbations more effectively than ICS alone. For severe asthma inadequately controlled with ICS+LABA, biologics such as omalizumab (Xolair®) may be added. Omalizumab, a monoclonal antibody targeting immunoglobulin E (IgE), inhibits allergic inflammation by preventing IgE binding to mast cells and basophils. Clinical studies show it reduces asthma attacks, improves lung function, and decreases corticosteroid dependence. While ICS+LABA is the primary treatment, omalizumab is often introduced when control remains insufficient. However, transcriptomic differences between these treatments remain unclear. Investigating mRNA expression changes may provide insights for optimizing asthma management. Research purposes: This study aims to compare transcriptomic expression profiles in patients with allergic asthma treated with ICS+LABA versus those receiving ICS+LABA with the addition of omalizumab. By analyzing RNA expression differences, the investigators seek to identify key molecular pathways influenced by these treatments, investigate omalizumab's impact on airway inflammation and immune regulation, and explore potential biomarkers for predicting treatment response. Understanding these transcriptomic changes may provide insights into optimizing therapeutic strategies and improving personalized asthma management. The main inclusion and exclusion conditions of the study: Participants were adults over 18 years old with a confirmed asthma diagnosis via a provocation test, receiving treatment according to GINA guidelines. The ICS+LABA group included asthma patients classified as stage III, while the ICS+LABA+omalizumab group consisted of patients with poor asthma control despite ICS+LABA therapy and elevated IgE levels. Exclusion criteria included current smokers, individuals with other lung diseases (e.g., lung cancer, COPD, bronchiectasis, ILD), or systemic conditions such as diabetes, hypertension, myocardial infarction, or heart failure. Those who declined participation were also excluded. Healthy controls had no history of asthma, systemic diseases, or medication use. Research Methods and Procedures: Pulmonary Function Tests PFTs followed American Thoracic Society guidelines using a Medical Graphics Corporation spirometer. Measured parameters included forced vital capacity (FVC), forced expiratory volume in one second (FEV1), mid-maximum expiratory flow (MMEF), and peak expiratory flow rate (PEFR). Blood Tests Comprehensive blood tests included RNA transcriptome analysis, allergen panel, IgE levels, complete blood count with differentials, hemoglobin, liver and kidney function tests, C-reactive protein (CRP), electrolytes, and chest X-rays. Asthma Control Assessment The Chinese-language Asthma Control Test (ACT) was used to evaluate asthma control, with scores ranging from 0 to 25, where higher scores indicate better management. Library Preparation and Sequencing RNA libraries were prepared using the TruSeq Stranded mRNA Library Prep Kit (Illumina), followed by mRNA extraction, fragmentation, cDNA synthesis, adapter ligation, and purification. Library quality was assessed using the Agilent Bioanalyzer 2100 system and real-time PCR. Sequencing was performed on the Illumina NovaSeq 6000 platform, generating 150 bp paired-end reads. Bioinformatics Analysis Raw sequence data were processed using Fastp for quality control, aligned to reference genomes using STAR, and quantified with RSEM. Differential gene expression was analyzed with edgeR, while Gene Ontology (GO) and KEGG pathway enrichment were performed using clusterProfiler and ShinyGO. RNA sequencing data are available at the National Center for Biotechnology Information (NCBI).

Conditions

Asthma Patients

Keywords

asthma; airway inflammation; omalizumab; RNA transcriptome

Outcome Measures

Primary Outcomes (1)

• Gene Expression Profiles and Differentially Expressed Genes (DEGs) Identified by RNA Sequencing

  Purified RNA was used to generate sequencing libraries with the TruSeq Stranded mRNA Library Prep Kit (Illumina, San Diego, CA, USA). mRNA was extracted from 1 µg of total RNA using oligo(dT)-coupled magnetic beads, followed by heat fragmentation into smaller fragments. First-strand cDNA synthesis was performed using reverse transcriptase and random primers, followed by second-strand synthesis. After adenylation at the 3' ends, adapter ligation, and purification with the AMPure XP system (Beckman Coulter, Beverly, USA), library quality was assessed using the Agilent Bioanalyzer 2100 system and real-time PCR. Qualified libraries were sequenced on the Illumina NovaSeq 6000 platform, generating 150 bp paired-end reads. Raw sequencing data were processed using the Fastp program (version 0.23.4) to remove adapter sequences and low-quality bases. Gene expression levels were quantified and normalized as transcripts per million (TPM). Differential gene expression analysis was performed by co

  From enrollment to the end of treatment at 12 weeks

Secondary Outcomes (8)

• Pulmonary function test

  From enrollment to the end of treatment at 12 weeks

• Serum IgE Concentration

  From enrollment to the end of treatment at 12 weeks

• Asthma control test

  From enrollment to the end of treatment at 12 weeks

• Body Mass Index (BMI)

  From enrollment to the end of treatment at 12 weeks

• Complete Blood Count (CBC)

  From enrollment to the end of treatment at 12 weeks

Study Arms (3)

ICS+LABA therapy

EXPERIMENTAL

ICS+LABA therapy refers to the combination of inhaled corticosteroids (ICS) and long-acting beta-agonists (LABA) in the treatment of asthma

Drug: Foster BDP/Formoterol

ICS+LABA+Omalizumab

EXPERIMENTAL

ICS+LABA+Omalizumab therapy is a combination treatment used for patients with moderate to severe asthma that is not well-controlled with inhaled corticosteroids (ICS) and long-acting beta-agonists (LABA) alone

Drug: Foster BDP/Formoterol; Drug: Omalizimab

control group

NO INTERVENTION

healthy subjects

Interventions

Foster BDP/Formoterol DRUG

Foster is a combination therapy containing beclometasone dipropionate (an inhaled corticosteroid, or ICS) and formoterol fumarate (a long-acting beta-agonist, or LABA), which is used for managing asthma and chronic obstructive pulmonary disease (COPD).

ICS+LABA therapy; ICS+LABA+Omalizumab

Omalizimab DRUG

Omalizumab is a monoclonal antibody that specifically targets immunoglobulin E (IgE), a key mediator in allergic asthma. By binding to free IgE in the bloodstream, omalizumab prevents it from attaching to FcεRI receptors on mast cells and basophils, inhibiting the allergic inflammatory cascade that contributes to asthma exacerbations and bronchoconstriction. This intervention is particularly useful in patients with severe allergic asthma, who have high levels of IgE and have not responded well to conventional therapies such as inhaled corticosteroids (ICS) and long-acting beta-agonists (LABA).

ICS+LABA+Omalizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• years old with a confirmed asthma diagnosis via a provocation test
• The treatment of asthma was according to GINA guideline. ICS with LABA group are patients of asthma presented as stage III. The adding of omalizuamb is patients with poor control of ICS with LABA with high IgE.

You may not qualify if:

• age less than 18 years old
• current smokers
• individuals with other lung diseases (such as lung cancer, chronic obstructive pulmonary disease, bronchiectasis, or interstitial lung disease)
• those with systemic conditions like diabetes, hypertension, myocardial infarction, or congestive heart failure.
• Individuals who opted not to participate were also excluded.

Sponsors & Collaborators

• Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation: lead

Study Sites (1)

Taipei Tzu Chi Hospital

New Taipei City, None Selected, 23142, Taiwan

Location

MeSH Terms

Conditions

Asthma

Condition Hierarchy (Ancestors)

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

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 25, 2025
• First Posted: March 11, 2025
• Study Start: January 1, 2023
• Primary Completion: December 31, 2023
• Study Completion: March 31, 2024
• Last Updated: March 11, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

TW (1)