Clinical trial NCT04961060: Drivers of Eosinophilic COPD Exacerbations
Official title: Drivers of Eosinophilic COPD Exacerbations
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: COPD Exacerbation
Eosinophilia
Lead sponsor: University Medical Center Groningen
Sponsor class: OTHER
Collaborators: name: Maastricht University
name: GlaxoSmithKline
First posted: 2021-07-14
Enrollment: 100
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients admitted to the UMCG or MUMC for a COPD exacerbation.

Brief summary: Main objective: investigate gene expression differences in nasal epithelium and sputum between eosinophilic COPD exacerbations and other subtypes.

Detailed description: Main objective: investigate gene expression differences in nasal epithelium and sputum between eosinophilic COPD exacerbations and other subtypes to better understand why some patients are more at risk for eosinophilic COPD exacerbations. Secondary objectives:

1. Investigate differences in microbiome composition and immunophenotyping profiles in peripheral blood per subtype.
2. Assess for clinical differences between all COPD exacerbation subtypes.
3. Assess if and how baseline meta-transcriptomics either in nasal epithelium or sputum and blood immunophenotyping can be utilized to predict COPD exacerbation subtype.
4. Determine if the microbiome in sputum and nasal epithelial material are comparable.
5. Determine if different subtypes of COPD exacerbations respond differently to standard treatment with oral prednisolone (40 mg daily) with or without antibiotics.
6. To evaluate if metabolic responses during recovery are different in patients with increased systemic inflammation compared to patients without systemic inflammation at exacerbation

Eligibility criteria: Inclusion Criteria:

1. COPD patient admitted to the hospital for an acute exacerbation of COPD
2. Physician diagnosed COPD according to the GOLD 2020 guidelines, including symptoms consistent with COPD, post-bronchodilator FEV1 \< 80% predicted and FEV1/FVC \< 70%.
3. Age \> 40 years.
4. Smoker or ex-smoker, ≥ 10 pack years of smoking.

Exclusion Criteria:

1. Current asthma, or prior physician diagnosis of asthma without a symptom- free interval of at least 10 years before the age of 40.
2. Chronic use of prednisolone.
3. Use of systemic corticosteroids ≥4 days prior to hospital admission.
4. Necessity (upon hospitalization) for non-invasive ventilation or ICU admission.
5. Pneumonia at presentation documented by chest roentgenography.
6. Any other clinically relevant lung disease deemed to interfere with the concept of the study design.
7. Allergy to systemic corticosteroids or to antibiotics.
8. Females of childbearing potential without an efficient contraception unless they meet the following definition of post-menopausal: 12 months of natural (spontaneous) amenorrhea or 6 months of spontaneous amenorrhea with serum FSH \>40 mIU/mL or the use of one or more of the following acceptable methods of contraception:

   1. Surgical sterilization (e.g. bilateral tubal ligation, hysterectomy).
   2. Hormonal contraception (implantable, patch, oral, injectable).
   3. Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/cream/suppository.
   4. Continuous abstinence
9. Pregnancy or lactation.
10. Known immunodeficiency.
11. Life expectancy less than 60 days

Primary outcomes:
measure: Change in gene expression profiles in sputum by RNA sequencing
timeFrame: At admission and after 6-8 weeks after discharge.
measure: Change in gene expression profiles in nasal epithelium by using RNA sequencing
timeFrame: At admission and after 6-8 weeks after discharge.
Secondary outcomes:
measure: Microbiome composition in sputum by using RNA sequencing.
timeFrame: At admission, at day 5 of admission and 6-8 weeks after discharge.
measure: Phenotype blood cell population by flow cytometry.
timeFrame: At admission, at day 5 of admission and 6-8 weeks after discharge.
measure: Phenotypic analysis of the T cell compartment by staining of whole blood or isolated peripheral blood mononuclear cells using antibodies
timeFrame: At admission, at day 5 of admission and 6-8 weeks after discharge.
measure: Comparison of microbiome composition in sputum and nasal epithelial material by RNA sequencing.
timeFrame: At admission and 6-8 weeks after discharge.
measure: Clinical differences between groups by the COPD Assessment Test (CAT).
timeFrame: Every day of hospital admission.
measure: Clinical differences between groups by peak flow measurements.
timeFrame: Every day of hospital admission.
Other outcomes:
Locations:
city: Maastricht
country: Netherlands
facility: University Maastricht
state: Limburg
city: Groningen
country: Netherlands
facility: Univesity Medical Center Groningen
Study officials:
affiliation: UMCG
name: Maarten van den Berge, PhD
role: PRINCIPAL_INVESTIGATOR
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