Analysis of Osteoimmune Interactions Linking Inflammation and Bone Destruction in Aggressive Periodontitis

NCT ID: NCT01993368

Last Updated: 2018-02-07

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: NA
• Total Enrollment: 8 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-11-30
• Study Completion Date: 2017-12-31

Brief Summary

Periodontitis are inflammatory diseases characterized by the destruction of the tooth-supporting bone due to increased bone resorption by osteoclasts (OCLs). Two forms are described: chronic periodontitis (CP) and aggressive periodontitis (AP) that differ by the severity and rapidity of bone loss, much more important for AP than CP. In both forms, the link with uncontrolled activation of the immune system is largely admitted. Despite the physiopathology of CP is fairly well studied, very few data are available regarding AP. The investigators aim is to understand the severity of AP by analyzing the proportion and action of immune and mesnchymal cells potentially involved in bone destruction, on biopsies of periodontal granulation tissue (surgical waste) and blood. Three groups of 20 patients will be included: affected with AP, CP or controls (necessitating an extraction of wisdom teeth).

Detailed Description

Context: Periodontitis are inflammatory diseases affecting the periodontium and characterized by the destruction of the tooth-supporting bone due to increased bone resorption by osteoclasts (OCLs). Two forms are described: chronic periodontitis (CP) and aggressive periodontitis (AP) that differ by the severity and rapidity of bone loss, much more important for AP than CP. In both forms, the link with uncontrolled activation of the immune system is largely admitted. But despite the physiopathology of CP is fairly well studied, very few data are available regarding AP. Based on the investigators previous studies, their hypothesis to explain this severity is the existence of a vicious circle involving immune cells, mesenchymal cells and OCLs, that would maintain and amplify inflammation and bone loss.

Study: this is a transversal, interventional and single-center study. It includes 3 groups of 20 patients: affected with AP, CP or controls (necessitating an extraction of wisdom teeth).

Aims: the investigators will compare the proportion of immune and mesenchymal cells in the 3 groups of patients to identify the populations potentially involved in bone destruction. The investigators will compare in vitro their capacity to induce OCL differentiation in order to determine their role in bone loss. The investigators will also compare the capacity of OCLs and mesenchymal cells to activate T cells, in order to determine their role in inflammation.

Methodology: patients will be recruited in the department of periodontology, CHU of Nice. After signing the informed consent, a biopsy of periodontal granulation tissue (surgical waste) will be collected during the usual treatment of these diseases, as well as a blood sample. Then, patients will leave the study. Cells from the biopsies will be analyzed by flow cytometry to determine the proportion of lymphocytic, monocytic and mesenchymal cells. In vitro, their capacity to induce OCL differentiation or to activate T cells will be determined. From the blood samples, OCLs will be generated to study their capacity to activate T cells.

Chronology of consultations and examinations: 3 visits are planned: (1) a routine visit corresponding to the usual treatment of the patient during which it is proposed to participate in the study, (2) a visit to obtaining consent, clinical examination, criteria verification and (3) a visit corresponding to the usual treatment in which will be collected tissue biopsies and blood.

Conditions

Aggressive Periodontitis; Chronic Periodontitis

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

chronic periodontitis

biopsy of periodontal granulation tissue (surgical waste)

Group Type: OTHER

flow cytometry

Intervention Type: OTHER

These populations will be identified by different combinations of antibodies to identify:

• T cell subsets (CD45, CD3, CD4, CD8, CD45RA, CD69, CD28, TCRαβ, TCRγδ, CD197, CD25, FoxP3), B cells (CD45, CD19, HLA-DR, IgA), cells NK (CD45, CD3, CD56).
• Monocyte subsets (CD45, CD11b, CD14, CD16, CD1c, HLA-DR)
• Mesenchymal stromal cells (CD45, HLA-ABC, CD105, CD90, CD73)

aggressive periodontitis (AP)

biopsy of periodontal granulation tissue (surgical waste)

Group Type: OTHER

flow cytometry

Intervention Type: OTHER

These populations will be identified by different combinations of antibodies to identify:

• T cell subsets (CD45, CD3, CD4, CD8, CD45RA, CD69, CD28, TCRαβ, TCRγδ, CD197, CD25, FoxP3), B cells (CD45, CD19, HLA-DR, IgA), cells NK (CD45, CD3, CD56).
• Monocyte subsets (CD45, CD11b, CD14, CD16, CD1c, HLA-DR)
• Mesenchymal stromal cells (CD45, HLA-ABC, CD105, CD90, CD73)

controls

necessitating an extraction of wisdom teeth

Group Type: OTHER

flow cytometry

Intervention Type: OTHER

These populations will be identified by different combinations of antibodies to identify:

• T cell subsets (CD45, CD3, CD4, CD8, CD45RA, CD69, CD28, TCRαβ, TCRγδ, CD197, CD25, FoxP3), B cells (CD45, CD19, HLA-DR, IgA), cells NK (CD45, CD3, CD56).
• Monocyte subsets (CD45, CD11b, CD14, CD16, CD1c, HLA-DR)
• Mesenchymal stromal cells (CD45, HLA-ABC, CD105, CD90, CD73)

Interventions

flow cytometry

These populations will be identified by different combinations of antibodies to identify:

• T cell subsets (CD45, CD3, CD4, CD8, CD45RA, CD69, CD28, TCRαβ, TCRγδ, CD197, CD25, FoxP3), B cells (CD45, CD19, HLA-DR, IgA), cells NK (CD45, CD3, CD56).
• Monocyte subsets (CD45, CD11b, CD14, CD16, CD1c, HLA-DR)
• Mesenchymal stromal cells (CD45, HLA-ABC, CD105, CD90, CD73)

Intervention Type: OTHER

Other Intervention Names

proportion of lymphocytes, myeloid and mesenchymal populations in the samples, as determined by flow cytometry.

Eligibility Criteria

Inclusion Criteria

• Young patients not suffering of any médical conditions
• Small amount of calculus detected
• Pocket depth >5mm
• Alveolar Bone loss >50%

• Evident presence of calculus above or under the gingiva
• Pocket depth >5mm

• Young patients in need of impacted wisdom teeth removal
• And not suffering of chronic or agressive periodontitis

Exclusion Criteria

• Patients with blood disorder
• Patients presenting with liver, kidney, or vascular disorder, and /or psychiatric disorder
• Patients who have allergies
• Patients taking biphosphonates, anticoagulant drugs, or anticonvulsivant
• Patients who have had a cancer of the mouth, and/or treated by radiotherapy
• Patients who have taken anti-inflammatory drugs, and/or anti-cancer drugs, and/or immuno-suppresive drugs in the past 6 months
• Patients who have had a periodontal treatment in the past 12 months
• Pregnant Women
• Patients juged difficult to follow by the investigator
• Vulnerable patients

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Centre Hospitalier Universitaire de Nice

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jérôme SURMENIAN, MD

Role: PRINCIPAL_INVESTIGATOR

Odontology Department, NIce University Hospital

Locations

Odontology Department, Nice Unversity Hospital

Nice, , France

Countries

France

Other Identifiers

13-PP-07

Identifier Type: -

Identifier Source: org_study_id