Interaction Between Immune Cells and Bacteria Associated With Periodontitis

NCT ID: NCT03225950

Last Updated: 2020-03-24

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

90 participants

Study Classification

OBSERVATIONAL

Study Start Date

2017-02-01

Study Completion Date

2020-03-23

Brief Summary

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This study evaluates the interaction between host immune cells and bacteria associated with periodontitis. It comprises biological material from donors with and without periodontal disease. Specifically, we collect a spit and blood sample to conduct in vitro stimulations and measurements of selected parameters related to periodontitis to clarify obscure areas in the immunologic pathogenesis of this disease.

Detailed Description

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Periodontitis is a prevalent, multifactorial inflammatory disease characterized by the interaction between microorganisms organized in biofilms on tooth surfaces and host immune cells, leading to an inflammatory destruction of the tooth-supporting tissues and - if left untreated - eventually tooth loss. Periodontitis affects up to 50% of the population in the United States of America, and is classified in an aggressive and a chronic form depending on genetic factors, age of onset, speed and severity of attachment loss.

The onset of periodontitis is caused by an immunologic imbalance between host immune cells and residing microorganisms in subgingival pockets. The host immune cells are capable of enhancing both a protective and a destructive inflammatory response towards the microorganisms through the release of inflammatory mediators e.i. proinflammatory and antiinflammatory cytokines.

The role of antibodies in periodontitis is also unclear. Some studies show an excessive antibody level against bacteria associated with periodontitis e.g. Porphyromonas gingivalis (P.g.).

In general, this study contributes to a profound understanding of the host immune cells role in the onset and pathogenesis of periodontitis by comparing healthy versus diseased donors immunologic responses toward pathogene and apathogene microorganisms and their genetic background.

Conditions

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Periodontal Diseases Periodontitis Aggressive Periodontitis Immunologic Disease Microbial Disease Periodontal Pocket Inflammation Inflammation Gum Dysbiosis Rheumatoid Arthritis Generalized Aggressive Periodontitis Generalized Chronic Periodontitis Chronic Periodontitis

Study Design

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Observational Model Type

CASE_CONTROL

Study Time Perspective

CROSS_SECTIONAL

Study Groups

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Chronic periodontitis donors

* Donors are medically healthy.
* Slow to moderate attachment loss and bone destruction.
* Good correlation between etiological factors and serverity of attachment loss.

In vitro stimulation of blood with periodontitis-associated- and control bacteria

Intervention Type OTHER

Peripheral mononuclear blood cells are stimulated with periodontitis-associated- and control bacteria to measure the amount of positive cytokine-producing cells.

Anti-CCP- and anti-P.g.-antibodies titers

Intervention Type DIAGNOSTIC_TEST

Anitbody titers will be measured in saliva and serum samples.

Analysis of selected single nucleotide polymorphisms (SNPs)

Intervention Type GENETIC

DNA obtained from saliva samples will be used to determine the genotype of the participants for selected SNPs.

periodontitis-associated bacteria presence

Intervention Type DIAGNOSTIC_TEST

Determination of the presence of periodontitis-associated bacteria e.i. Porphyromonas gingivalis in saliva and blood samples.

Aggressive periodontitis donors

* Donors are medically healthy.
* Rapid attachment loss and bone destruction.
* Familial aggregation.
* No correlation between etiological factors and serverity of attachment loss.

In vitro stimulation of blood with periodontitis-associated- and control bacteria

Intervention Type OTHER

Peripheral mononuclear blood cells are stimulated with periodontitis-associated- and control bacteria to measure the amount of positive cytokine-producing cells.

Anti-CCP- and anti-P.g.-antibodies titers

Intervention Type DIAGNOSTIC_TEST

Anitbody titers will be measured in saliva and serum samples.

Analysis of selected single nucleotide polymorphisms (SNPs)

Intervention Type GENETIC

DNA obtained from saliva samples will be used to determine the genotype of the participants for selected SNPs.

periodontitis-associated bacteria presence

Intervention Type DIAGNOSTIC_TEST

Determination of the presence of periodontitis-associated bacteria e.i. Porphyromonas gingivalis in saliva and blood samples.

Control donors

* Donors are medically healthy.
* No sign of inflammatory conditions.

In vitro stimulation of blood with periodontitis-associated- and control bacteria

Intervention Type OTHER

Peripheral mononuclear blood cells are stimulated with periodontitis-associated- and control bacteria to measure the amount of positive cytokine-producing cells.

Anti-CCP- and anti-P.g.-antibodies titers

Intervention Type DIAGNOSTIC_TEST

Anitbody titers will be measured in saliva and serum samples.

Analysis of selected single nucleotide polymorphisms (SNPs)

Intervention Type GENETIC

DNA obtained from saliva samples will be used to determine the genotype of the participants for selected SNPs.

periodontitis-associated bacteria presence

Intervention Type DIAGNOSTIC_TEST

Determination of the presence of periodontitis-associated bacteria e.i. Porphyromonas gingivalis in saliva and blood samples.

Interventions

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In vitro stimulation of blood with periodontitis-associated- and control bacteria

Peripheral mononuclear blood cells are stimulated with periodontitis-associated- and control bacteria to measure the amount of positive cytokine-producing cells.

Intervention Type OTHER

Anti-CCP- and anti-P.g.-antibodies titers

Anitbody titers will be measured in saliva and serum samples.

Intervention Type DIAGNOSTIC_TEST

Analysis of selected single nucleotide polymorphisms (SNPs)

DNA obtained from saliva samples will be used to determine the genotype of the participants for selected SNPs.

Intervention Type GENETIC

periodontitis-associated bacteria presence

Determination of the presence of periodontitis-associated bacteria e.i. Porphyromonas gingivalis in saliva and blood samples.

Intervention Type DIAGNOSTIC_TEST

Eligibility Criteria

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Inclusion Criteria

* 50-60 years of age.
* Interproximal attachment loss at minimum 3 teeth besides molars and incisors.
* Clinical attachment loss at minimum 10 sites identified by bleeding and pus upon probing.
* Visible radiographic bone loss.
* Medically healthy donors.


* 19-40 years of age.
* Interproximal attachment loss at minimum 3 teeth besides molars and incisors.
* Clinical attachment loss at minimum 10 sites identified by bleeding and pus upon probing.
* Visible radiographic bone loss.
* Medically healthy donors.


* No sign of inflammatory conditions or other general systemic diseases.
* Medically healthy donors.

Exclusion Criteria

* Pregnant and breastfeeding.
* Antibiotic treatment within 6 months.
* Suffer from periodontal manifestations caused by systemic diseases e.i. genetic diseases, haematologic anomalies or syndromes.
Minimum Eligible Age

19 Years

Maximum Eligible Age

60 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Copenhagen University Hospital, Denmark

OTHER

Sponsor Role collaborator

University of Copenhagen

OTHER

Sponsor Role lead

Responsible Party

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Anne Katrine Danielsen

Research Assistant

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Palle Holmstrup, DDS, PhD, Dr Odont

Role: STUDY_DIRECTOR

University of Copenhagen

Claus Henrik Nielsen, PhD, MSc, MD

Role: STUDY_DIRECTOR

Institute for Inflammation Research, Center for Rheumatology and Spine Diseases, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.

Locations

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Institute for Inflammation Research, Center for Rheumatology and Spine Diseases, Rigshospitalet, Copenhagen University Hospital.

Copenhagen, , Denmark

Site Status

Section for Periodontology, Microbiology and Community Dentistry, Department of Odontology, Faculty of Health and Medical Sciences, University of Copenhagen

Copenhagen, , Denmark

Site Status

Countries

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Denmark

References

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Bartold PM, Van Dyke TE. Periodontitis: a host-mediated disruption of microbial homeostasis. Unlearning learned concepts. Periodontol 2000. 2013 Jun;62(1):203-17. doi: 10.1111/j.1600-0757.2012.00450.x.

Reference Type BACKGROUND
PMID: 23574467 (View on PubMed)

Neely AL, Holford TR, Loe H, Anerud A, Boysen H. The natural history of periodontal disease in man. Risk factors for progression of attachment loss in individuals receiving no oral health care. J Periodontol. 2001 Aug;72(8):1006-15. doi: 10.1902/jop.2001.72.8.1006.

Reference Type BACKGROUND
PMID: 11525431 (View on PubMed)

Eke PI, Dye BA, Wei L, Slade GD, Thornton-Evans GO, Borgnakke WS, Taylor GW, Page RC, Beck JD, Genco RJ. Update on Prevalence of Periodontitis in Adults in the United States: NHANES 2009 to 2012. J Periodontol. 2015 May;86(5):611-22. doi: 10.1902/jop.2015.140520. Epub 2015 Feb 17.

Reference Type BACKGROUND
PMID: 25688694 (View on PubMed)

Armitage GC. Development of a classification system for periodontal diseases and conditions. Northwest Dent. 2000 Nov-Dec;79(6):31-5.

Reference Type BACKGROUND
PMID: 11413609 (View on PubMed)

Haffajee AD, Socransky SS, Patel MR, Song X. Microbial complexes in supragingival plaque. Oral Microbiol Immunol. 2008 Jun;23(3):196-205. doi: 10.1111/j.1399-302X.2007.00411.x.

Reference Type BACKGROUND
PMID: 18402605 (View on PubMed)

Damgaard C, Holmstrup P, Van Dyke TE, Nielsen CH. The complement system and its role in the pathogenesis of periodontitis: current concepts. J Periodontal Res. 2015 Jun;50(3):283-93. doi: 10.1111/jre.12209. Epub 2014 Jul 5.

Reference Type BACKGROUND
PMID: 25040158 (View on PubMed)

Liu YC, Lerner UH, Teng YT. Cytokine responses against periodontal infection: protective and destructive roles. Periodontol 2000. 2010 Feb;52(1):163-206. doi: 10.1111/j.1600-0757.2009.00321.x. No abstract available.

Reference Type BACKGROUND
PMID: 20017801 (View on PubMed)

Kinane DF, Preshaw PM, Loos BG; Working Group 2 of Seventh European Workshop on Periodontology. Host-response: understanding the cellular and molecular mechanisms of host-microbial interactions--consensus of the Seventh European Workshop on Periodontology. J Clin Periodontol. 2011 Mar;38 Suppl 11:44-8. doi: 10.1111/j.1600-051X.2010.01682.x.

Reference Type BACKGROUND
PMID: 21323703 (View on PubMed)

Pussinen PJ, Jousilahti P, Alfthan G, Palosuo T, Asikainen S, Salomaa V. Antibodies to periodontal pathogens are associated with coronary heart disease. Arterioscler Thromb Vasc Biol. 2003 Jul 1;23(7):1250-4. doi: 10.1161/01.ATV.0000072969.71452.87. Epub 2003 Apr 24.

Reference Type BACKGROUND
PMID: 12714435 (View on PubMed)

Pussinen PJ, Nyyssonen K, Alfthan G, Salonen R, Laukkanen JA, Salonen JT. Serum antibody levels to Actinobacillus actinomycetemcomitans predict the risk for coronary heart disease. Arterioscler Thromb Vasc Biol. 2005 Apr;25(4):833-8. doi: 10.1161/01.ATV.0000157982.69663.59. Epub 2005 Feb 3.

Reference Type BACKGROUND
PMID: 15692101 (View on PubMed)

Berglundh T, Donati M. Aspects of adaptive host response in periodontitis. J Clin Periodontol. 2005;32 Suppl 6:87-107. doi: 10.1111/j.1600-051X.2005.00820.x.

Reference Type BACKGROUND
PMID: 16128832 (View on PubMed)

Fillatreau S. Cytokine-producing B cells as regulators of pathogenic and protective immune responses. Ann Rheum Dis. 2013 Apr;72 Suppl 2:ii80-4. doi: 10.1136/annrheumdis-2012-202253. Epub 2012 Dec 19.

Reference Type BACKGROUND
PMID: 23253921 (View on PubMed)

Belstrom D, Paster BJ, Fiehn NE, Bardow A, Holmstrup P. Salivary bacterial fingerprints of established oral disease revealed by the Human Oral Microbe Identification using Next Generation Sequencing (HOMINGS) technique. J Oral Microbiol. 2016 Jan 14;8:30170. doi: 10.3402/jom.v8.30170. eCollection 2016.

Reference Type BACKGROUND
PMID: 26782357 (View on PubMed)

Belstrom D, Holmstrup P, Bardow A, Kokaras A, Fiehn NE, Paster BJ. Comparative analysis of bacterial profiles in unstimulated and stimulated saliva samples. J Oral Microbiol. 2016 Mar 16;8:30112. doi: 10.3402/jom.v8.30112. eCollection 2016.

Reference Type BACKGROUND
PMID: 26987356 (View on PubMed)

Danielsen AK, Damgaard C, Massarenti L, Ostrup P, Riis Hansen P, Holmstrup P, Nielsen CH. B-cell cytokine responses to Porphyromonas gingivalis in patients with periodontitis and healthy controls. J Periodontol. 2023 Aug;94(8):997-1007. doi: 10.1002/JPER.22-0438. Epub 2023 Mar 5.

Reference Type DERIVED
PMID: 36715211 (View on PubMed)

Other Identifiers

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H-16024734

Identifier Type: -

Identifier Source: org_study_id

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