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

NCT02928367 | Unknown

• 1 other identifier: NL57847.018.16
• Study Type: observational
• Target: 231
• Locations: 1 country
• Sites: 1

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

Conditions

Pneumonia

Outcome Measures

Primary Outcomes (1)

• Alterations in leukocyte DNA methylation

  day 0

Secondary Outcomes (3)

• Composition and function of the gut and nasopharyngeal microbiota

  day 0

• Alterations in leukocyte DNA methylation

  day 28

• Composition and function of the gut and nasopharyngeal microbiota

  day 28

Study Arms (2)

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; Other: nasopharyngeal swab; Other: blood draw

Healthy subjects

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

Other: rectal swab; Other: nasopharyngeal swab; Other: blood draw

Interventions

rectal swab OTHER

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

Healthy subjects; Pneumonia patients

nasopharyngeal swab OTHER

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

Healthy subjects; Pneumonia patients

blood draw OTHER

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

Healthy subjects; Pneumonia patients

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• 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:

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA): lead

Study Sites (1)

Academic Medical Center - University of Amsterdam

Amsterdam, North Holland, 1105 AZ, Netherlands

RECRUITING

Related Publications (3)

• 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.

  PMID: 35100411 DERIVED

• 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.

  PMID: 34399830 DERIVED

• 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.

  PMID: 33935163 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

feces, nasofaryngeal swabs, blood

MeSH Terms

Conditions

Pneumonia

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Tom van der Poll, MD, PhD

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

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Bastiaan W Haak, MD

CONTACT

5665247; b.w.haak@amc.nl

Xanthe Brands, MD

CONTACT

5665247; x.brands@amc.nl

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: prof. dr.

Study Record Dates

• First Submitted: October 6, 2016
• First Posted: October 10, 2016
• Study Start: October 1, 2016
• Primary Completion: October 1, 2020
• Study Completion: October 1, 2020
• Last Updated: January 9, 2020

Record last verified: 2020-01

Locations

NL (1)