Blood Exosomal Multi-omics and Lung Radiomics for Predicting Efficacy and Prognosis of Severe Eosinophilic ACOS With Biologics (ACOS)
21. maj 2026 opdateret af: Yang Jin, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
Blood Exosomal Multi-omics and Lung Radiomics for Predicting Efficacy and Prognosis of Severe Eosinophilic ACOS (Asthma-COPD Overlap Syndrome) Treated With Different Biologics: A Real-World Observational Study
Firstly, to screen blood exosomal multi-omics (transcriptomics, proteomics, metabolomics) and lung radiomics (HRCT, Xe129MRI) biomarkers that can predict efficacy and prognosis in severe eosinophilic ACOS (asthma-COPD overlap) patients treated with different biologics (benralizumab, mepolizumab, dupilumab).
Then, to prospectively follow patients for 48 weeks after biologic initiation and collect clinical data, blood samples, and imaging features.
Finally, to build a multi-dimensional predictive model for efficacy and prognosis of severe eosinophilic ACOS.
Studieoversigt
Status
Ikke rekrutterer endnu
Betingelser
Detaljeret beskrivelse
Firstly, eligible patients (age ≥14 years, diagnosis of severe eosinophilic ACOS, blood eosinophils ≥150/μL within 3 months or ≥300/μL within 1 year, and clinician decision to start a biologic) will be enrolled. Exclusion criteria include concurrent trial participation, allergy to biologics, malignancy, or prior biologic use.
Then, patients are followed for 48 weeks after the first biologic dose. Visits occur at weeks 0, 1, 2, 4, 8, 16, 24, 40, and 48. Data collected include demographics, medical history, ACQ-6, MiniAQLQ, pre-BD FEV1, exacerbations, medication use, adverse events, and blood routine tests (residual samples for exosome analysis). HRCT and Xe129MRI are optional.
Next, the primary outcome is the composite endpoint of efficacy and prognosis at week 48, defined as: no ACOS exacerbation, no oral corticosteroids, pre-BD FEV1 improvement ≥100 mL from baseline, and ACQ-6 score <1.5 (or ≤0.75). Secondary outcomes include changes in ACQ-6, FEV1, annualized exacerbation rate, MiniAQLQ, OCS dose reduction, and blood exosomal multi-omics and lung radiomics biomarkers.
Finally, statistical analyses include descriptive statistics, paired t-test/Wilcoxon, ANOVA/Kruskal-Wallis, mixed-effects model for repeated measures (MMRM), differential expression analysis (DESeq2/limma), pathway enrichment, machine learning (LASSO, random forest), ROC curves, logistic regression, and Cox regression. A total of 500 patients will be enrolled from multiple centers in China.
Undersøgelsestype
Observationel
Tilmelding (Anslået)
500
Kontakter og lokationer
Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.
Studiekontakt
- Navn: Qi Huang
- Telefonnummer: +86 15827329098
- E-mail: huangqi66@126.com
Studiesteder
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Hubei
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Wuhan, Hubei, Kina, 430022
- Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
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Kontakt:
- Qi Huang
- Telefonnummer: +86 15827329098
- E-mail: huangqi66@126.com
-
-
Deltagelseskriterier
Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.
Berettigelseskriterier
Aldre berettiget til at studere
- Barn
- Voksen
- Ældre voksen
Tager imod sunde frivillige
Ingen
Prøveudtagningsmetode
Ikke-sandsynlighedsprøve
Studiebefolkning
Patients aged 14 years or older with a confirmed diagnosis of severe eosinophilic ACOS (asthma-COPD overlap) who are prescribed a biologic (benralizumab, mepolizumab, or dupilumab) by their treating physician according to routine clinical practice.
The study population is recruited from outpatient and inpatient respiratory departments of multiple hospitals in China, including Union Hospital (Tongji Medical College, Huazhong University of Science and Technology) and its collaborating centers.
Beskrivelse
Inclusion Criteria:
- Age ≥ 14 years
- Clinician decision to start biologic (benralizumab, mepolizumab, or dupilumab) for severe eosinophilic ACOS
- Blood eosinophils ≥150/μL within 3 months prior to informed consent, or ≥300/μL within 1 year prior
- Signed written informed consent
Exclusion Criteria:
- Currently participating in any other interventional clinical trial
- Known allergy or hypersensitivity to any component of the study drugs
- Any type of malignancy
- Prior or current biologic treatment for ACOS
Studieplan
Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
Kohorter og interventioner
Gruppe / kohorte |
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Benralizumab Group
Patients with severe eosinophilic ACOS receiving benralizumab as prescribed by their treating physician according to routine clinical practice.
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Mepolizumab Group
Patients with severe eosinophilic ACOS receiving mepolizumab as prescribed by their treating physician according to routine clinical practice.
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Dupilumab Group
Patients with severe eosinophilic ACOS receiving dupilumab as prescribed by their treating physician according to routine clinical practice.
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Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
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Composite efficacy and prognosis endpoint at week 48 in severe eosinophilic ACOS
Tidsramme: 48 weeks after the first dose of biologic
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We define the composite endpoint as achieving ALL of the following at week 48: (1) no ACOS exacerbation (worsening of respiratory symptoms requiring systemic corticosteroids ≥3 days, emergency visit <24h, or hospitalization ≥24h); (2) no use of oral corticosteroids (OCS); (3) pre-bronchodilator FEV1 improvement ≥100 mL from baseline; (4) ACQ-6 score <1.5 (or ≤0.75).
The proportion of patients meeting all four criteria will be calculated.
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48 weeks after the first dose of biologic
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Sekundære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
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Change in Asthma Control Questionnaire-6 (ACQ-6) score
Tidsramme: Baseline to 48 weeks
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ACQ-6 is a validated questionnaire (6 items, score 0-6, lower = better control).
Change from baseline will be assessed at weeks 1,2,4,8,16,24,40,48.
Mean difference and standard deviation will be reported.
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Baseline to 48 weeks
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Change in pre-bronchodilator FEV1 (mL)
Tidsramme: Baseline to 48 weeks
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FEV1 (forced expiratory volume in 1 second) will be measured using spirometry according to international standards (ATS/ERS).
Change in mL from baseline will be calculated at weeks 8, 16, and 48.
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Baseline to 48 weeks
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Annualized rate of ACOS exacerbations
Tidsramme: 48 weeks
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Number of ACOS exacerbations per year during the 48-week follow-up.
Exacerbation defined as worsening of respiratory symptoms requiring systemic corticosteroids (≥3 days), emergency department visit (<24 hours), or hospitalization (≥24 hours).
Rate = (total exacerbations × 365.25) / follow-up days.
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48 weeks
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Change in Mini Asthma Quality of Life Questionnaire (MiniAQLQ) score
Tidsramme: Baseline to 48 weeks
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MiniAQLQ is a 15-item questionnaire (score 1-7, higher = better quality of life).
Change from baseline will be assessed at weeks 8, 16, 24, and 48.
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Baseline to 48 weeks
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Change in blood exosomal multi-omics biomarkers
Tidsramme: Baseline to 48 weeks
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Residual blood from routine tests (2-3 mL per time point at weeks 0,4,8,16,24,40,48) will be used to isolate exosomes.
Transcriptomics (RNA-seq), proteomics (mass spectrometry), and metabolomics (LC-MS) profiles will be compared between baseline and week 48.
Differentially expressed features (|log2FC|>1, FDR<0.05) will be reported.
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Baseline to 48 weeks
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Change in lung radiomics features
Tidsramme: Baseline to 48 weeks
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For patients who undergo HRCT or Xe129MRI (optional), radiomics features (e.g., texture, shape, intensity) will be extracted using standard software.
Changes from baseline to week 24 and 48 will be analyzed.
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Baseline to 48 weeks
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Samarbejdspartnere og efterforskere
Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.
Datoer for undersøgelser
Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.
Studer store datoer
Studiestart (Anslået)
1. juni 2026
Primær færdiggørelse (Anslået)
1. juni 2028
Studieafslutning (Anslået)
1. juli 2028
Datoer for studieregistrering
Først indsendt
17. maj 2026
Først indsendt, der opfyldte QC-kriterier
21. maj 2026
Først opslået (Faktiske)
22. maj 2026
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Faktiske)
22. maj 2026
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
21. maj 2026
Sidst verificeret
1. maj 2026
Mere information
Begreber relateret til denne undersøgelse
Andre undersøgelses-id-numre
- XHJY202605
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