The Effect of Leukocyte Dna mEthylation and micRoBIOME Diversity on Host Defense Mechanisms During Community-acquired Pneumonia (ELDER-BIOME) (ELDER-BIOME)

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ClinicalTrials.gov Identifier: NCT02928367

Recruitment Status : Unknown

Verified January 2020 by T. van der Poll, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA).
Recruitment status was: Recruiting

First Posted : October 10, 2016

Last Update Posted : January 9, 2020

View this study on Beta.ClinicalTrials.gov

Sponsor:

Information provided by (Responsible Party):

T. van der Poll, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Study Description

Brief 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.

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

Condition or disease	Intervention/treatment
Pneumonia	Other: rectal swab Other: nasopharyngeal swab Other: blood draw

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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.

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:

1. 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

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Study Type :	Observational
Estimated Enrollment :	231 participants
Observational Model:	Case-Control
Time Perspective:	Prospective
Official Title:	The Effect of Leukocyte Dna mEthylation and micRoBIOME Diversity on Host Defense Mechanisms During Community-acquired Pneumonia
Actual Study Start Date :	October 1, 2016
Estimated Primary Completion Date :	October 1, 2020
Estimated Study Completion Date :	October 1, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Pneumonia

U.S. FDA Resources

Groups and Cohorts

Group/Cohort	Intervention/treatment
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)	Other: rectal swab rectal swab at baseline visit (2x) and at day 28 (2x) OR rectal swab at single timepoint (2x) (healthy volunteers) Other: nasopharyngeal swab nasopharyngeal swab at baseline visit (1x) and at day 28 (1x) OR nasopharyngeal swab at single timepoint (2x) (healthy volunteers) Other: blood draw blood draw at baseline visit (45ml) and at day 28 (45ml) (pneumonia patients) OR single blood draw (70ml) (healthy volunteers)
Healthy subjects rectal swab (2x) nasopharyngeal swab (2x) blood draw (70ml)	Other: rectal swab rectal swab at baseline visit (2x) and at day 28 (2x) OR rectal swab at single timepoint (2x) (healthy volunteers) Other: nasopharyngeal swab nasopharyngeal swab at baseline visit (1x) and at day 28 (1x) OR nasopharyngeal swab at single timepoint (2x) (healthy volunteers) Other: blood draw blood draw at baseline visit (45ml) and at day 28 (45ml) (pneumonia patients) OR single blood draw (70ml) (healthy volunteers)

Group/Cohort

Intervention/treatment

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)

Other: rectal swab

rectal swab at baseline visit (2x) and at day 28 (2x) OR rectal swab at single timepoint (2x) (healthy volunteers)

Other: nasopharyngeal swab

nasopharyngeal swab at baseline visit (1x) and at day 28 (1x) OR nasopharyngeal swab at single timepoint (2x) (healthy volunteers)

Other: blood draw

blood draw at baseline visit (45ml) and at day 28 (45ml) (pneumonia patients) OR single blood draw (70ml) (healthy volunteers)

Healthy subjects

rectal swab (2x) nasopharyngeal swab (2x) blood draw (70ml)

Other: rectal swab

rectal swab at baseline visit (2x) and at day 28 (2x) OR rectal swab at single timepoint (2x) (healthy volunteers)

Other: nasopharyngeal swab

nasopharyngeal swab at baseline visit (1x) and at day 28 (1x) OR nasopharyngeal swab at single timepoint (2x) (healthy volunteers)

Other: blood draw

blood draw at baseline visit (45ml) and at day 28 (45ml) (pneumonia patients) OR single blood draw (70ml) (healthy volunteers)

Outcome Measures

Primary Outcome Measures :

Alterations in leukocyte DNA methylation [ Time Frame: day 0 ]

Secondary Outcome Measures :

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 ]

Biospecimen Retention: Samples With DNA

feces, nasofaryngeal swabs, blood

Eligibility Criteria

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:	18 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	Yes
Sampling Method:	Probability Sample

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:

Criteria

Inclusion Criteria:

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).

Exclusion Criteria:

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.

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02928367

Contacts

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Contact: Bastiaan W Haak, MD	5665247 ext 020	b.w.haak@amc.nl
Contact: Xanthe Brands, MD	5665247 ext 020	x.brands@amc.nl

Locations

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Netherlands
Academic Medical Center - University of Amsterdam	Recruiting
Amsterdam, Noord-Holland, Netherlands, 1105 AZ
Contact: Tom van der Poll, MD, PhD t.vanderpoll@amc.uva.nl
Sub-Investigator: W. Joost Wiersinga, MD, PhD, MBA
Sub-Investigator: Brendon P Scicluna, PhD

Sponsors and Collaborators

Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Investigators

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Principal Investigator:	Tom van der Poll, MD, PhD	Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Brands 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.

Brands 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.

Brands 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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Responsible Party:	T. van der Poll, prof. dr., Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
ClinicalTrials.gov Identifier:	NCT02928367
Other Study ID Numbers:	NL57847.018.16
First Posted:	October 10, 2016 Key Record Dates
Last Update Posted:	January 9, 2020
Last Verified:	January 2020

Additional relevant MeSH terms:

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Pneumonia Respiratory Tract Infections Infections Lung Diseases Respiratory Tract Diseases

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