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Interaction Between Immune Cells and Bacteria Associated With Periodontitis

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ClinicalTrials.gov Identifier: NCT03225950
Recruitment Status : Recruiting
First Posted : July 21, 2017
Last Update Posted : July 25, 2017
Sponsor:
Collaborators:
Copenhagen University Hospital, Denmark
International Association of Dental Research
Danish Dental Association
Information provided by (Responsible Party):
Anne Katrine Danielsen, University of Copenhagen

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
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 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 Type : Observational
Estimated Enrollment : 170 participants
Observational Model: Case-Control
Time Perspective: Cross-Sectional
Official Title: Interaction Between Immune Cells and Bacteria Associated With Periodontitis
Actual Study Start Date : February 1, 2017
Estimated Primary Completion Date : August 29, 2020
Estimated Study Completion Date : August 29, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Drug Reactions

Group/Cohort 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.




Primary Outcome Measures :
  1. periodontitis-associated- and control bacterial stimulation of host immune cells. [ Time Frame: 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. [ Time Frame: 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. [ Time Frame: 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. [ Time Frame: 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. [ Time Frame: 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. [ Time Frame: Aug. 2020 ]
    Determination of the presence of other periodontal bacteria through RT-qPCR assays.


Biospecimen Retention:   Samples With DNA
Saliva, whole blood, peripheral mononuclear blood cells, serum, plasma.


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Ages Eligible for Study:   19 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
This study includes 170 participants, which are legally competent e.i. above 18 years of age and general decision competent. The participants are divided into three groups: 1) Participants with chronic periodontitis (n=35), 2) participants with aggressive periodontitis (n=35) and 3) healthy participants without periodontal disease (n=100). The participants are recruited from the Department of Odontology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark and assigned to a group in accordance with the periodontal disease classification system in 1999 American Academy of Periodontology.
Criteria

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.

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): NCT03225950


Contacts
Contact: Anne Katrine Danielsen, No Degree 004522670101 rbs334@alumni.ku.dk
Contact: Christian Damgaard, DDS, PhD 004525323832 chrd@sund.ku.dk

Locations
Denmark
Institute for Inflammation Research, Center for Rheumatology and Spine Diseases, Rigshospitalet, Copenhagen University Hospital. Completed
Copenhagen, Denmark, 2200
Section for Periodontology, Microbiology and Community Dentistry, Department of Odontology, Faculty of Health and Medical Sciences, University of Copenhagen Recruiting
Copenhagen, Denmark, 2200
Contact: Anne Katrine Danielsen, No degree    004522670101    rbs334@alumni.ku.dk   
Contact: Christian Damgaard, DDS, PhD    004525323832    chrd@sund.ku.dk   
Principal Investigator: Palle Holmstrup, DDS, PhD, Dr Odont         
Sponsors and Collaborators
University of Copenhagen
Copenhagen University Hospital, Denmark
International Association of Dental Research
Danish Dental Association
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.

Publications:

Responsible Party: Anne Katrine Danielsen, Research Assistant, University of Copenhagen
ClinicalTrials.gov Identifier: NCT03225950     History of Changes
Other Study ID Numbers: H-16024734
First Posted: July 21, 2017    Key Record Dates
Last Update Posted: July 25, 2017
Last Verified: July 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: IPD will not be available to other researchers in accordance with our approved Human Subjects Protection application in Denmark.

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Anne Katrine Danielsen, University of Copenhagen:
Periodontal disease
Periodontitis
Aggressive periodontitis
Dysbiosis
Inflammation
Regulation
Cytokines
Bacteria
Porphyromonas gingivalis
Saliva
Anti-CCP
Peptidyl arginine deiminases
Single nucleotide polymorphisms

Additional relevant MeSH terms:
Periodontal Diseases
Gingival Diseases
Immune System Diseases
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Mouth Diseases
Stomatognathic Diseases
Arthritis, Rheumatoid
Inflammation
Periodontitis
Aggression
Chronic Periodontitis
Aggressive Periodontitis
Dysbiosis
Periodontal Pocket
Gingivitis
Arthritis
Pathologic Processes
Behavioral Symptoms
Antibodies
Immunologic Factors
Physiological Effects of Drugs