Ignite Creation Date:
2025-12-25 @ 12:43 AM
Ignite Modification Date:
2026-01-25 @ 6:08 AM
Study NCT ID:
NCT02928367
Status:
UNKNOWN
Last Update Posted:
2020-01-09
First Post:
2016-10-06
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
The Effect of Leukocyte Dna mEthylation and micRoBIOME Diversity on Host Defense Mechanisms During Community-acquired Pneumonia (ELDER-BIOME)
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D011014', 'term': 'Pneumonia'}], 'ancestors': [{'id': 'D012141', 'term': 'Respiratory Tract Infections'}, {'id': 'D007239', 'term': 'Infections'}, {'id': 'D008171', 'term': 'Lung Diseases'}, {'id': 'D012140', 'term': 'Respiratory Tract Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D001800', 'term': 'Blood Specimen Collection'}], 'ancestors': [{'id': 'D013048', 'term': 'Specimen Handling'}, {'id': 'D019411', 'term': 'Clinical Laboratory Techniques'}, {'id': 'D019937', 'term': 'Diagnostic Techniques and Procedures'}, {'id': 'D003933', 'term': 'Diagnosis'}, {'id': 'D011677', 'term': 'Punctures'}, {'id': 'D013514', 'term': 'Surgical Procedures, Operative'}, {'id': 'D008919', 'term': 'Investigative Techniques'}]}}, 'protocolSection': {'designModule': {'bioSpec': {'retention': 'SAMPLES_WITH_DNA', 'description': 'feces, nasofaryngeal swabs, blood'}, 'studyType': 'OBSERVATIONAL', 'designInfo': {'timePerspective': 'PROSPECTIVE', 'observationalModel': 'CASE_CONTROL'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 231}, 'patientRegistry': False}, 'statusModule': {'overallStatus': 'UNKNOWN', 'lastKnownStatus': 'RECRUITING', 'startDateStruct': {'date': '2016-10-01', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2020-01', 'completionDateStruct': {'date': '2020-10-01', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2020-01-07', 'studyFirstSubmitDate': '2016-10-06', 'studyFirstSubmitQcDate': '2016-10-07', 'lastUpdatePostDateStruct': {'date': '2020-01-09', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2016-10-10', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2020-10-01', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Alterations in leukocyte DNA methylation', 'timeFrame': 'day 0'}], 'secondaryOutcomes': [{'measure': 'Composition and function of the gut and nasopharyngeal microbiota', 'timeFrame': 'day 0'}, {'measure': 'Alterations in leukocyte DNA methylation', 'timeFrame': 'day 28'}, {'measure': 'Composition and function of the gut and nasopharyngeal microbiota', 'timeFrame': 'day 28'}]}, 'oversightModule': {'oversightHasDmc': False}, 'conditionsModule': {'conditions': ['Pneumonia']}, 'referencesModule': {'references': [{'pmid': '35100411', 'type': 'DERIVED', 'citation': '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': '34399830', 'type': 'DERIVED', 'citation': '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': '33935163', 'type': 'DERIVED', 'citation': '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.'}]}, 'descriptionModule': {'briefSummary': '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.\n\nWhile 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.\n\nThis 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', 'detailedDescription': 'Rationale:\n\nCommunity-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.\n\nWhile 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.\n\nThis 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.\n\nPrimary Objectives:\n\n1. 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.\n2. To determine the composition and function of the gut and respiratory microbiota in patients with CAP.\n\nSecondary Objective:\n\n1\\. To assess the influence of the gut microbiota on leukocyte DNA methylation in patients with CAP\n\nStudy design:\n\nObservational study among patients with CAP at the Emergency Department and Internal Medicine Ward of the Academic Medical Center Amsterdam\n\nStudy population:\n\n231 CAP patients and 115 healthy subjects above 18 years of age.\n\nMethods:\n\nFrom 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.\n\nNature and extent of the burden and risks associated with participation, benefit and group relatedness:\n\nParticipating 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.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'samplingMethod': 'PROBABILITY_SAMPLE', 'studyPopulation': '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:', 'healthyVolunteers': True, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Clinical suspicion of a new episode of acute respiratory tract infection\n* Primary reason for presentation is clinical suspicion of a new episode of acute respiratory infection; admission to the hospital is NOT a requirement\n* Evident new or progressive infiltrate, consolidation, cavitation, or pleural effusion on the chest X ray or CT scan made for diagnostic (non-research) purposes\n* Onset of the following symptoms within the last 7 days:\n* At least one respiratory symptom (cough, sore throat, runny or congested nose, dyspnea)\n* At least one systemic symptom (fever, headache, muscle ache, sweats or chills or tiredness).\n\nExclusion Criteria:\n\n* Patient lacks capacity to provide informed consent\n* No informed consent is provided by patient\n* Patient has been transferred from another hospital\n* Patient is enrolled in an interventional clinical study of an anti-infective or immunomodulatory therapy\n* Patient has received any type of oral or systemic antibiotics for more than 48 hours prior to hospital presentation.'}, 'identificationModule': {'nctId': 'NCT02928367', 'acronym': 'ELDER-BIOME', 'briefTitle': 'The Effect of Leukocyte Dna mEthylation and micRoBIOME Diversity on Host Defense Mechanisms During Community-acquired Pneumonia (ELDER-BIOME)', 'organization': {'class': 'OTHER', 'fullName': 'Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)'}, 'officialTitle': 'The Effect of Leukocyte Dna mEthylation and micRoBIOME Diversity on Host Defense Mechanisms During Community-acquired Pneumonia', 'orgStudyIdInfo': {'id': 'NL57847.018.16'}}, 'armsInterventionsModule': {'armGroups': [{'label': 'Pneumonia patients', 'description': '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)', 'interventionNames': ['Other: rectal swab', 'Other: nasopharyngeal swab', 'Other: blood draw']}, {'label': 'Healthy subjects', 'description': 'rectal swab (2x) nasopharyngeal swab (2x) blood draw (70ml)', 'interventionNames': ['Other: rectal swab', 'Other: nasopharyngeal swab', 'Other: blood draw']}], 'interventions': [{'name': 'rectal swab', 'type': 'OTHER', 'description': 'rectal swab at baseline visit (2x) and at day 28 (2x) OR rectal swab at single timepoint (2x) (healthy volunteers)', 'armGroupLabels': ['Healthy subjects', 'Pneumonia patients']}, {'name': 'nasopharyngeal swab', 'type': 'OTHER', 'description': 'nasopharyngeal swab at baseline visit (1x) and at day 28 (1x) OR nasopharyngeal swab at single timepoint (2x) (healthy volunteers)', 'armGroupLabels': ['Healthy subjects', 'Pneumonia patients']}, {'name': 'blood draw', 'type': 'OTHER', 'description': 'blood draw at baseline visit (45ml) and at day 28 (45ml) (pneumonia patients) OR single blood draw (70ml) (healthy volunteers)', 'armGroupLabels': ['Healthy subjects', 'Pneumonia patients']}]}, 'contactsLocationsModule': {'locations': [{'zip': '1105 AZ', 'city': 'Amsterdam', 'state': 'North Holland', 'status': 'RECRUITING', 'country': 'Netherlands', 'contacts': [{'name': 'Tom van der Poll, MD, PhD', 'role': 'CONTACT', 'email': 't.vanderpoll@amc.uva.nl'}, {'name': 'W. Joost Wiersinga, MD, PhD, MBA', 'role': 'SUB_INVESTIGATOR'}, {'name': 'Brendon P Scicluna, PhD', 'role': 'SUB_INVESTIGATOR'}], 'facility': 'Academic Medical Center - University of Amsterdam', 'geoPoint': {'lat': 52.37403, 'lon': 4.88969}}], 'centralContacts': [{'name': 'Bastiaan W Haak, MD', 'role': 'CONTACT', 'email': 'b.w.haak@amc.nl', 'phone': '5665247', 'phoneExt': '020'}, {'name': 'Xanthe Brands, MD', 'role': 'CONTACT', 'email': 'x.brands@amc.nl', 'phone': '5665247', 'phoneExt': '020'}], 'overallOfficials': [{'name': 'Tom van der Poll, MD, PhD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)', 'class': 'OTHER'}, 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'prof. dr.', 'investigatorFullName': 'T. van der Poll', 'investigatorAffiliation': 'Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)'}}}}