PneumoniaELDER-BIOMENCT02928367
The Effect of Leukocyte Dna mEthylation and micRoBIOME Diversity on Host Defense Mechanisms During Community-acquired Pneumonia (ELDER-BIOME)
An observational study of Pneumonia, run by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) at 1 site in Netherlands.
Trial summary
Community-acquired pneumonia (CAP) represents a major health care problem and mortality and morbidity associated with severe pneumonia remain considerable, despite state of the art care. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Pneumonia
- What is being tested?
- rectal swab, nasopharyngeal swab and blood draw
- How many people
- 231 participants
- Where
- 1 siteNetherlands
- Study dates
- 1 Oct 2016to 1 Oct 2020
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Adults presenting at the Academic Medical Center with a suspected new episode of community acquired pneumonia will be screened for eligibility for the ELDER-BIOME study according to the following scheme:
Who may be able to join
- Clinical suspicion of a new episode of acute respiratory tract infection
- Primary reason for presentation is clinical suspicion of a new episode of acute respiratory infection; admission to the hospital is NOT a requirement
- Evident new or progressive infiltrate, consolidation, cavitation, or pleural effusion on the chest X ray or CT scan made for diagnostic (non-research) purposes
- Onset of the following symptoms within the last 7 days:
- At least one respiratory symptom (cough, sore throat, runny or congested nose, dyspnea)
- At least one systemic symptom (fever, headache, muscle ache, sweats or chills or tiredness).
Who cannot join
- Patient lacks capacity to provide informed consent
- No informed consent is provided by patient
- Patient has been transferred from another hospital
- Patient is enrolled in an interventional clinical study of an anti-infective or immunomodulatory therapy
- Patient has received any type of oral or systemic antibiotics for more than 48 hours prior to hospital presentation.
Trial locations and contacts
1 site in 1 country.
Netherlands1 site, 1 recruiting
- Recruiting
Academic Medical Center - University of Amsterdam
Amsterdam, North Holland, 1105 AZ
Tom van der Poll, MD, PhD, t.vanderpoll@amc.uva.nl
W. Joost Wiersinga, MD, PhD, MBA
About this study
Official title: The Effect of Leukocyte Dna mEthylation and micRoBIOME Diversity on Host Defense Mechanisms During Community-acquired Pneumonia
Community-acquired pneumonia (CAP) represents a major health care problem and mortality and morbidity associated with severe pneumonia remain considerable, despite state of the art care.
While the role of altered DNA methylation in cancer has been widely studied, knowledge of its impact on antibacterial defense is highly limited. In addition, recent preclinical studies showed that the gut and respiratory microbiota contributes to host defense against bacterial pneumonia.
This study aims to explore a completely novel research area linking the extent of DNA methylation in blood leukocyte (monocytes and neutrophils) and function of gut and respiratory microbiota on the influence of innate immune responses to and host defense against CAP
Read the detailed description
Rationale:
Community-acquired pneumonia (CAP) represents a major health care problem and mortality and morbidity associated with severe pneumonia remain considerable, despite state of the art care.
While the role of altered DNA methylation in cancer has been widely studied, knowledge of its impact on antibacterial defense is highly limited. In addition, recent preclinical studies showed that the gut and respiratory microbiota contributes to host defense against bacterial pneumonia.
This study aims to explore a completely novel research area linking the extent of DNA methylation in blood leukocyte (monocytes and neutrophils) and function of gut and respiratory microbiota on the influence of innate immune responses to and host defense against CAP.
Primary Objectives:
- To obtain insight in the role of altered DNA methylation in blood leukocytes (monocytes and neutrophils) in innate immune responses and host defense in patients with CAP.
- To determine the composition and function of the gut and respiratory microbiota in patients with CAP.
Secondary Objective:
- To assess the influence of the gut microbiota on leukocyte DNA methylation in patients with CAP
Study design:
Observational study among patients with CAP at the Emergency Department and Internal Medicine Ward of the Academic Medical Center Amsterdam
Study population:
231 CAP patients and 115 healthy subjects above 18 years of age.
Methods:
From above mentioned patients and healthy volunteers, a maximum of 90 ml of blood will be drawn to analyze DNA methylation patterns of purified monocytes and neutrophils, which will be analyzed in connection with DNA methyltransferase and ten eleven translocation (TET) activity, RNA gene expression and a selection of standard innate immune function tests. Moreover, isolated monocytes and neutrophils from admission samples will be stimulated in vitro with Streptococcus pneumoniae and Klebsiella pneumoniae. In addition, rectal and nasopharyngeal swabs will be obtained to investigate the role of the gut and respiratory microbiota composition and function. Patient material will be obtained upon inclusion and on day 28, when patients will be seen in the outpatient clinic for follow up.
Nature and extent of the burden and risks associated with participation, benefit and group relatedness:
Participating in this observational study will not benefit the participants and healthy volunteers. The study will provide information about the influence of leukocyte DNA methylation as well as the gut and respiratory microbiota on host defense mechanisms during CAP. The knowledge obtained can potentially benefit CAP patients in the future by providing alternative immune modulating treatment options that modify the host response. The burden and risks for patients participating in the ELDER-BIOME study is minimal. The investigators will take 90ml of blood, 4 rectal swabs and 2 nasopharyngeal swabs divided over two time-points (day of presentation and day 28 post presentation). Healthy volunteers will be subjected to one blood draw (70 ml) and 2 rectal - and 2 nasopharyngeal swabs at one time-point.
- Conditions
- Pneumonia
- Being tested
- rectal swab, nasopharyngeal swab, blood draw
- Medical subject headings
- Pneumonia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
rectal swabOther
rectal swab at baseline visit (2x) and at day 28 (2x) OR rectal swab at single timepoint (2x) (healthy volunteers)
nasopharyngeal swabOther
nasopharyngeal swab at baseline visit (1x) and at day 28 (1x) OR nasopharyngeal swab at single timepoint (2x) (healthy volunteers)
blood drawOther
blood draw at baseline visit (45ml) and at day 28 (45ml) (pneumonia patients) OR single blood draw (70ml) (healthy volunteers)
| Study group | Role | What they receive |
|---|---|---|
| Pneumonia patients | rectal swab (4x) divided over two time points (day 0 and day 28) nasopharyngeal swab (2x) divided over two time points (day 0 and day 28) blood draw (90ml) divided over two time points (day 0 and day 28) Receives: Other: rectal swab; Other: nasopharyngeal swab; Other: blood draw | |
| Healthy subjects | rectal swab (2x) nasopharyngeal swab (2x) blood draw (70ml) Receives: Other: rectal swab; Other: nasopharyngeal swab; Other: blood draw |
What is being measured
The primary outcome is the main question the study is designed to answer.
Alterations in leukocyte DNA methylation
Measured: day 0
Secondary outcomes (3)
Composition and function of the gut and nasopharyngeal microbiota
Measured: day 0
Alterations in leukocyte DNA methylation
Measured: day 28
Composition and function of the gut and nasopharyngeal microbiota
Measured: day 28
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Oct 2016 (estimated)
- Study start1 Oct 2016
- Primary completion1 Oct 2020 (estimated)
- Study completion1 Oct 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for PneumoniaStudies of the same condition, open and under way.
- More trials run by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 231 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, T. van der Poll, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
- Investigators
- Tom van der Poll, MD, PhD, Principal investigator, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02928367
- Sponsor's protocol ID
- NL57847.018.16
- Acronym
- ELDER-BIOME
- Status last verified
- Jan 2020
- First submitted
- 6 Oct 2016
- Last updated
- 9 Jan 2020
- Results posted
- No
- Data monitoring committee
- No
Publications
Michels EHA, Chouchane O, de Brabander J, de Vos AF, Faber DR, Douma RA, Smit ER, Wiersinga WJ, van den Biggelaar M, van der Poll T, Hoogendijk AJ. Proteomic profiling of neutrophils and plasma in community-acquired pneumonia reveals crucial proteins in diverse biological pathways linked to clinical outcome. Front Immunol. 2024 Oct 18;15:1470383. doi: 10.3389/fimmu.2024.1470383. eCollection 2024.
PubMed 39493755Brands X, van Engelen TSR, de Vries FMC, Haak BW, Klarenbeek AM, Kanglie MMNP, van den Berk IAH, Schuurman AR, Peters-Sengers H, Otto NA, Faber DR, Lutter R, Scicluna BP, Stoker J, Prins JM, Joost Wiersinga W, van der Poll T. Association of Hyperferritinemia With Distinct Host Response Aberrations in Patients With Community-Acquired Pneumonia. J Infect Dis. 2022 Jun 1;225(11):2023-2032. doi: 10.1093/infdis/jiac013.
PubMed 35100411Brands X, Haak BW, Klarenbeek AM, Butler J, Uhel F, Qin W, Otto NA, Jakobs ME, Faber DR, Lutter R, Wiersinga WJ, van der Poll T, Scicluna BP. An epigenetic and transcriptomic signature of immune tolerance in human monocytes through multi-omics integration. Genome Med. 2021 Aug 16;13(1):131. doi: 10.1186/s13073-021-00948-1.
PubMed 34399830Brands X, de Vries FMC, Uhel F, Haak BW, Peters-Sengers H, Schuurman AR, van Engelen TSR, Lutter R, Cremer OL, Bonten MJ, Schultz MJ, Scicluna BP, van der Poll T; MARS Consortium. Plasma Ferritin as Marker of Macrophage Activation-Like Syndrome in Critically Ill Patients With Community-Acquired Pneumonia. Crit Care Med. 2021 Nov 1;49(11):1901-1911. doi: 10.1097/CCM.0000000000005072.
PubMed 33935163
Study at a glance
From the registry record, last updated by the sponsor on 9 Jan 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Leukocyte Dna mEthylation and micRoBIOME Diversity on Host Defense Mechanisms During Community-acquired Pneumonia
- ClinicalTrials.gov ID
- NCT02928367
- Acronym / sponsor ID
- ELDER-BIOME / NL57847.018.16
- Conditions
- Pneumonia
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 231 participants (estimated)
- Lead sponsor
- Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)University, hospital or other
- Study start
- 1 Oct 2016 (actual)
- Primary completion
- 1 Oct 2020 (estimated)
- Study completion
- 1 Oct 2020 (estimated)
- First posted
- 10 Oct 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Community-acquired pneumonia (CAP) represents a major health care problem and mortality and morbidity associated with severe pneumonia remain considerable, despite state of the art care.
While the role of altered DNA methylation in cancer has been widely studied, knowledge of its impact on antibacterial defense is highly limited. In addition, recent preclinical studies showed that the gut and respiratory microbiota contributes to host defense against bacterial pneumonia.
This study aims to explore a completely novel research area linking the extent of DNA methylation in blood leukocyte (monocytes and neutrophils) and function of gut and respiratory microbiota on the influence of innate immune responses to and host defense against CAP
Detailed description
Rationale:
Community-acquired pneumonia (CAP) represents a major health care problem and mortality and morbidity associated with severe pneumonia remain considerable, despite state of the art care.
While the role of altered DNA methylation in cancer has been widely studied, knowledge of its impact on antibacterial defense is highly limited. In addition, recent preclinical studies showed that the gut and respiratory microbiota contributes to host defense against bacterial pneumonia.
This study aims to explore a completely novel research area linking the extent of DNA methylation in blood leukocyte (monocytes and neutrophils) and function of gut and respiratory microbiota on the influence of innate immune responses to and host defense against CAP.
Primary Objectives:
- To obtain insight in the role of altered DNA methylation in blood leukocytes (monocytes and neutrophils) in innate immune responses and host defense in patients with CAP.
- To determine the composition and function of the gut and respiratory microbiota in patients with CAP.
Secondary Objective:
- To assess the influence of the gut microbiota on leukocyte DNA methylation in patients with CAP
Study design:
Observational study among patients with CAP at the Emergency Department and Internal Medicine Ward of the Academic Medical Center Amsterdam
Study population:
231 CAP patients and 115 healthy subjects above 18 years of age.
Methods:
From above mentioned patients and healthy volunteers, a maximum of 90 ml of blood will be drawn to analyze DNA methylation patterns of purified monocytes and neutrophils, which will be analyzed in connection with DNA methyltransferase and ten eleven translocation (TET) activity, RNA gene expression and a selection of standard innate immune function tests. Moreover, isolated monocytes and neutrophils from admission samples will be stimulated in vitro with Streptococcus pneumoniae and Klebsiella pneumoniae. In addition, rectal and nasopharyngeal swabs will be obtained to investigate the role of the gut and respiratory microbiota composition and function. Patient material will be obtained upon inclusion and on day 28, when patients will be seen in the outpatient clinic for follow up.
Nature and extent of the burden and risks associated with participation, benefit and group relatedness:
Participating in this observational study will not benefit the participants and healthy volunteers. The study will provide information about the influence of leukocyte DNA methylation as well as the gut and respiratory microbiota on host defense mechanisms during CAP. The knowledge obtained can potentially benefit CAP patients in the future by providing alternative immune modulating treatment options that modify the host response. The burden and risks for patients participating in the ELDER-BIOME study is minimal. The investigators will take 90ml of blood, 4 rectal swabs and 2 nasopharyngeal swabs divided over two time-points (day of presentation and day 28 post presentation). Healthy volunteers will be subjected to one blood draw (70 ml) and 2 rectal - and 2 nasopharyngeal swabs at one time-point.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Pneumonia patients | – | Other: rectal swab, Other: nasopharyngeal swab, Other: blood drawrectal swab (4x) divided over two time points (day 0 and day 28) nasopharyngeal swab (2x) divided over two time points (day 0 and day 28) blood draw (90ml) divided over two time points (day 0 and day 28) |
| Healthy subjects | – | Other: rectal swab, Other: nasopharyngeal swab, Other: blood drawrectal swab (2x) nasopharyngeal swab (2x) blood draw (70ml) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Adults presenting at the Academic Medical Center with a suspected new episode of community acquired pneumonia will be screened for eligibility for the ELDER-BIOME study according to the following scheme:
Key inclusion criteria (6 listed)
- Clinical suspicion of a new episode of acute respiratory tract infection
- Primary reason for presentation is clinical suspicion of a new episode of acute respiratory infection; admission to the hospital is NOT a requirement
- Evident new or progressive infiltrate, consolidation, cavitation, or pleural effusion on the chest X ray or CT scan made for diagnostic (non-research) purposes
- Onset of the following symptoms within the last 7 days:
- At least one respiratory symptom (cough, sore throat, runny or congested nose, dyspnea)
Key exclusion criteria (5 listed)
- Patient lacks capacity to provide informed consent
- No informed consent is provided by patient
- Patient has been transferred from another hospital
- Patient is enrolled in an interventional clinical study of an anti-infective or immunomodulatory therapy
- Patient has received any type of oral or systemic antibiotics for more than 48 hours prior to hospital presentation.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| rectal swabrectal swab at baseline visit (2x) and at day 28 (2x) OR rectal swab at single timepoint (2x) (healthy volunteers) | Other | Healthy subjects, Pneumonia patients |
| nasopharyngeal swabnasopharyngeal swab at baseline visit (1x) and at day 28 (1x) OR nasopharyngeal swab at single timepoint (2x) (healthy volunteers) | Other | Healthy subjects, Pneumonia patients |
| blood drawblood draw at baseline visit (45ml) and at day 28 (45ml) (pneumonia patients) OR single blood draw (70ml) (healthy volunteers) | Other | Healthy subjects, Pneumonia patients |
Primary outcome
Alterations in leukocyte DNA methylation
Time frame: day 0
3 secondary outcomes
Composition and function of the gut and nasopharyngeal microbiota
Time frame: day 0
Alterations in leukocyte DNA methylation
Time frame: day 28
Composition and function of the gut and nasopharyngeal microbiota
Time frame: day 28
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jan 2020.
- Derived from this study: PubMed 39493755Michels EHA, Chouchane O, de Brabander J, de Vos AF, Faber DR, Douma RA, Smit ER, Wiersinga WJ, van den Biggelaar M, van der Poll T, Hoogendijk AJ. Proteomic profiling of neutrophils and plasma in community-acquired pneumonia reveals crucial proteins in diverse biological pathways linked to clinical outcome. Front Immunol. 2024 Oct 18;15:1470383. doi: 10.3389/fimmu.2024.1470383. eCollection 2024.
- Derived from this study: PubMed 35100411Brands X, van Engelen TSR, de Vries FMC, Haak BW, Klarenbeek AM, Kanglie MMNP, van den Berk IAH, Schuurman AR, Peters-Sengers H, Otto NA, Faber DR, Lutter R, Scicluna BP, Stoker J, Prins JM, Joost Wiersinga W, van der Poll T. Association of Hyperferritinemia With Distinct Host Response Aberrations in Patients With Community-Acquired Pneumonia. J Infect Dis. 2022 Jun 1;225(11):2023-2032. doi: 10.1093/infdis/jiac013.
- Derived from this study: PubMed 34399830Brands X, Haak BW, Klarenbeek AM, Butler J, Uhel F, Qin W, Otto NA, Jakobs ME, Faber DR, Lutter R, Wiersinga WJ, van der Poll T, Scicluna BP. An epigenetic and transcriptomic signature of immune tolerance in human monocytes through multi-omics integration. Genome Med. 2021 Aug 16;13(1):131. doi: 10.1186/s13073-021-00948-1.
- Derived from this study: PubMed 33935163Brands X, de Vries FMC, Uhel F, Haak BW, Peters-Sengers H, Schuurman AR, van Engelen TSR, Lutter R, Cremer OL, Bonten MJ, Schultz MJ, Scicluna BP, van der Poll T; MARS Consortium. Plasma Ferritin as Marker of Macrophage Activation-Like Syndrome in Critically Ill Patients With Community-Acquired Pneumonia. Crit Care Med. 2021 Nov 1;49(11):1901-1911. doi: 10.1097/CCM.0000000000005072.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Tom van der Poll, MD, PhD principal investigator
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Pneumonia, run by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 9 Jan 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Bastiaan W Haak, MD (5665247 ext. 020, b.w.haak@amc.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Alterations in leukocyte DNA methylation (time frame: day 0). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02928367, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Jan 2020.