Drivers of Eosinophilic COPD Exacerbations (DICE)

July 2, 2021 updated by: Maarten van den Berge, University Medical Center Groningen
Main objective: investigate gene expression differences in nasal epithelium and sputum between eosinophilic COPD exacerbations and other subtypes.

Study Overview

Status

Recruiting

Conditions

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

Study Type

Observational

Enrollment (Anticipated)

100

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Netherlands
      • Groningen, Netherlands, 9713 GZ
    • Limburg
      • Maastricht, Limburg, Netherlands, 6229 GT
        • Not yet recruiting
        • University Maastricht
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

40 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Patients admitted to the UMCG or MUMC for a COPD exacerbation.

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Eosinophilic exacerbation
COPD exacerbation associated with eosinophilia.
Viral exacerbation
COPD exacerbation associated with viral infection.
Bacterial exacerbation
COPD exacerbation associated bacterial infection.
Pauci-inflammatory exacerbation
Pauci-inflammatory COPD exacerbation

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in gene expression profiles in sputum by RNA sequencing
Time Frame: At admission and after 6-8 weeks after discharge.
Change in gene expression profiles in sputum between the four groups using RNA sequencing. The differences between the expression levels of transcripts (counts) will be analyzed.
At admission and after 6-8 weeks after discharge.
Change in gene expression profiles in nasal epithelium by using RNA sequencing
Time Frame: At admission and after 6-8 weeks after discharge.
Change in gene expression profilesin nasal epithelium between the four groups using RNA sequencing. The differences between the expression levels of transcripts (counts) will be analyzed.
At admission and after 6-8 weeks after discharge.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Microbiome composition in sputum by using RNA sequencing.
Time Frame: At admission, at day 5 of admission and 6-8 weeks after discharge.
Differences in microbiome composition in sputum between the four groups by using RNA sequencing.
At admission, at day 5 of admission and 6-8 weeks after discharge.
Phenotype blood cell population by flow cytometry.
Time Frame: At admission, at day 5 of admission and 6-8 weeks after discharge.
Differences in blood cell population between the four groups as measured by flow cytometry.
At admission, at day 5 of admission and 6-8 weeks after discharge.
Phenotypic analysis of the T cell compartment by staining of whole blood or isolated peripheral blood mononuclear cells using antibodies
Time Frame: At admission, at day 5 of admission and 6-8 weeks after discharge.
Differences in the T cell compartment between the four groups by staining of whole blood or isolated peripheral blood mononuclear cells using antibodies.
At admission, at day 5 of admission and 6-8 weeks after discharge.
Comparison of microbiome composition in sputum and nasal epithelial material by RNA sequencing.
Time Frame: At admission and 6-8 weeks after discharge.
Measure microbiome composition in sputum and nasal epithelium by RNA sequencing. Compare them by the bacterial taxa which are significantly different between groups
At admission and 6-8 weeks after discharge.
Clinical differences between groups by the COPD Assessment Test (CAT).
Time Frame: Every day of hospital admission.
Differences in number of participants per group with a high impact of COPD related symptoms as assessed by the CAT.
Every day of hospital admission.
Clinical differences between groups by peak flow measurements.
Time Frame: Every day of hospital admission.
Differences in number of participants per group with a low peak expiratory flow rate as measured by a handheld peak flow meter.
Every day of hospital admission.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Medical Center Groningen

Collaborators

GlaxoSmithKline
Maastricht University

Investigators

  • Principal Investigator: Maarten van den Berge, PhD, UMCG

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ANTICIPATED)

July 1, 2021

Primary Completion (ANTICIPATED)

September 1, 2024

Study Completion (ANTICIPATED)

January 1, 2025

Study Registration Dates

First Submitted

April 28, 2021

First Submitted That Met QC Criteria

July 2, 2021

First Posted (ACTUAL)

July 14, 2021

Study Record Updates

Last Update Posted (ACTUAL)

July 14, 2021

Last Update Submitted That Met QC Criteria

July 2, 2021

Last Verified

July 1, 2021

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NL75151.042.20

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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