Interaction Between Immune Cells and Bacteria Associated With Periodontitis

Sponsor
University of Copenhagen (Other)
Overall Status
Completed
CT.gov ID
NCT03225950
Collaborator
Copenhagen University Hospital, Denmark (Other)
90
2
37.7
45
1.2

Study Details

Study Description

Brief Summary

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.

Condition or Disease Intervention/Treatment Phase
  • Other: In vitro stimulation of blood with periodontitis-associated- and control bacteria
  • Diagnostic Test: Anti-CCP- and anti-P.g.-antibodies titers
  • Genetic: Analysis of selected single nucleotide polymorphisms (SNPs)
  • Diagnostic Test: periodontitis-associated bacteria presence

Detailed Description

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.

Study Design

Study Type:
Observational
Actual Enrollment :
90 participants
Observational Model:
Case-Control
Time Perspective:
Cross-Sectional
Official Title:
Interaction Between Immune Cells and Bacteria Associated With Periodontitis
Actual Study Start Date :
Feb 1, 2017
Actual Primary Completion Date :
Oct 12, 2018
Actual Study Completion Date :
Mar 23, 2020

Arms and Interventions

Arm Intervention/Treatment
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.

Other: 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.

Diagnostic Test: Anti-CCP- and anti-P.g.-antibodies titers
Anitbody titers will be measured in saliva and serum samples.

Genetic: 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.

Diagnostic Test: periodontitis-associated bacteria presence
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.

Other: 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.

Diagnostic Test: Anti-CCP- and anti-P.g.-antibodies titers
Anitbody titers will be measured in saliva and serum samples.

Genetic: 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.

Diagnostic Test: periodontitis-associated bacteria presence
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.

Other: 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.

Diagnostic Test: Anti-CCP- and anti-P.g.-antibodies titers
Anitbody titers will be measured in saliva and serum samples.

Genetic: 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.

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

Outcome Measures

Primary Outcome Measures

  1. periodontitis-associated- and control bacterial stimulation of host immune cells. [Aug. 2020]

    Identification and determination of the amount of cytokine-producing immune cells when stimulated with bacteria associated with periodontitis including pro- and antiinflammatory cytokines. Genuses: Porphyromonas, Prevotella, Eikenella, Aggregatibacter, Actinomyces, Lactobacillus, Bifidobacterium, Rothia.

  2. Anti-cyclic citrullinated peptides (anti-CCP) antibodies titers. [Aug. 2020]

    Determination of the prevalence of anti-CCP-positive periodontitis patients through measure of anti-CCP antibody titers in serum samples and correlation with the level of antibodies to P. gingivalis, and to the abundancy of the bacterium in saliva.

  3. P. gingivalis presence and related antibodies. [Aug. 2020]

    Determination of P. gingivalis presence in saliva and serum samples through RT-qPCR and determination of the level of antibodies towards the bacterium using in-house Luminex-based technology.

  4. Single nucleotide polymorphism (SNP) analysis. [Aug. 2020]

    Investigation of the potential association between periodontitis and selected polymorphisms in the PADI genes using multiplex bead-based SNP assays with the Luminex technology.

Secondary Outcome Measures

  1. Cytokine profile in saliva. [Aug. 2020]

    Determination of the cytokine profile in saliva samples from subject with periodontitis and healthy controls with Luminex based technology.

  2. Presence of other periodontal bacteria. [Aug. 2020]

    Determination of the presence of other periodontal bacteria through RT-qPCR assays.

Eligibility Criteria

Criteria

Ages Eligible for Study:
19 Years to 60 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
Yes
Inclusion criteria for chronic periodontitis donors:
  • 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.

Inclusion criteria for aggressive periodontitis 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.

Inclusion criteria for healthy donors: (age: 19-40 years; 50-60 years)

  • No sign of inflammatory conditions or other general systemic diseases.

  • Medically healthy donors.

Exclusion criteria for all groups:
  • Pregnant and breastfeeding.

  • Antibiotic treatment within 6 months.

  • Suffer from periodontal manifestations caused by systemic diseases e.i. genetic diseases, haematologic anomalies or syndromes.

Contacts and Locations

Locations

Site City State Country Postal Code
1 Institute for Inflammation Research, Center for Rheumatology and Spine Diseases, Rigshospitalet, Copenhagen University Hospital. Copenhagen Denmark 2200
2 Section for Periodontology, Microbiology and Community Dentistry, Department of Odontology, Faculty of Health and Medical Sciences, University of Copenhagen Copenhagen Denmark 2200

Sponsors and Collaborators

  • University of Copenhagen
  • Copenhagen University Hospital, Denmark

Investigators

  • Study Director: Palle Holmstrup, DDS, PhD, Dr Odont, University of Copenhagen
  • Study Director: Claus Henrik Nielsen, PhD, MSc, MD, Institute for Inflammation Research, Center for Rheumatology and Spine Diseases, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.

Study Documents (Full-Text)

None provided.

More Information

Publications

Responsible Party:
Anne Katrine Danielsen, Research Assistant, University of Copenhagen
ClinicalTrials.gov Identifier:
NCT03225950
Other Study ID Numbers:
  • H-16024734
First Posted:
Jul 21, 2017
Last Update Posted:
Mar 24, 2020
Last Verified:
Oct 1, 2018
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Anne Katrine Danielsen, Research Assistant, University of Copenhagen
Additional relevant MeSH terms:

Study Results

No Results Posted as of Mar 24, 2020