Evaluation of the Effects of Immune Cells on Periodontal Healing

Periodontitis Clinical Trial

— EMTA  

Official title:

Evaluation of the Effects of Initial Macrophage and Th17 Cell Activities on the Healing Following Periodontal Phase I Therapy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04792372
• Other study ID #: TheMacPer
• Status: Completed
• Phase: N/A
• Start date: February 23, 2021
• Est. completion date: June 30, 2022

Study information

• Verified date: August 2022
• Source: Biruni University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Periodontitis is an inflammatory disease with an infectious character, where, as the result of the host response to a dysbiotic microflora, attachment and bone loss occur. The host response and the healing period following the treatment differs among individuals, but the reason behind is not fully understood. The macrophages and T cells play an important role in the immune response and in the pathogenesis of periodontal diseases, but their role in the healing following periodontal therapy is not known. In this study, we aim to reveal the effects of initial macrophage and T cell activities in the gingival tissue on the differences of the response to phase I periodontal treatment.

42 individuals will be included in the study. Granulation tissue samples will be collected from two separate deep pockets of each individual, initially. At the same session, full-mouth scaling and root debridement will be conducted. Saliva, subgingival biofilm and gingival crevicular fluid (GCF) samples will also be collected, initially, and at the 2nd, 6th, 12th and 24th weeks. At the same appointments, periodontal parameters will be recorded. When the clinical procedures are concluded, the samples will be sent to Turku University with dry ice. Tissue and GCF concentrations of related cytokines will be analyzed with Luminex. The density of macrophage types will be defined by immunoblot analysis of related markers. Macrophage subpopulations in tissues will be specified by proteomics. Likewise, quantities of periodontal pathogens will be evaluated with DNA isolation and next generation sequencing.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 52
• Est. completion date: June 30, 2022
• Est. primary completion date: August 31, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• moderate to severe periodontitis

• having at least two pockets = 6 mm

• systemic healthy

Exclusion Criteria:

• received periodontal treatment prior to study

• received antibiotic or antiinflammatory drugs in the last 6 months

• pregnant or in lactation

Related Conditions & MeSH terms

• Periodontitis

Intervention

Procedure:
• Initial periodontal treatment
Conventional periodontal treatment (scaling and root debridement) will be conducted

Locations

Country	Name	City	State
Turkey	Biruni University	Istanbul

Sponsors (3)

Lead Sponsor	Collaborator
Biruni University	The Scientific and Technological Research Council of Turkey, University of Turku

Country where clinical trial is conducted

Turkey, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Probable pocket depth (PPD)	distance between the gingival margin and pocket base (mm); full-mouth scores, 6 sites per tooth	baseline, 2nd, 6th, 12th and 24th weeks following therapy
Primary	Change in Bleeding on probing (BoP)	visual inspection, dichotomous; full-mouth, 6 sites per tooth; change in positive sites %	baseline, 2nd, 6th, 12th and 24th weeks following therapy
Primary	Baseline macrophage related cytokine concentrations in granulation tissue samples	two pockets (=6mm; BoP+) of each individual; Luminex: monocyte chemoattractant protein (MCP)-1, -2, -3, -4; macrophage derived chemokine (MDC); macrophage inhibitory factor (MIF), monokine induced by gamma interferon (MIG), macrophage inflammatory protein (MIP)-1a, interferon ?-induced protein (IP)-10, CD163, TWEAK, BAFF concentrations (pg/mL); each will be correlated with the change in probable pocket depth and bleeding on probing scores	Samples will be obtained during the intervention and will be kept in -80oC until immunohistochemical analysis which will be carried out through study completion, 6-9 months
Primary	Baseline Th17-pathway related cytokine concentrations in granulation tissue samples	two pockets (=6mm; BoP+) of each individual; Luminex: Interleukin (IL)-1ß, -4, -6, -10, -17A, -17F, -21, -22, -23, -25, -31, -33, interferon (IFN)-?, soluble cluster of differentiation 40 ligand (sCD-40L), tumor necrosis factor (TNF)-? concentrations (pg/mL); each will be correlated with the change in probable pocket depth and bleeding on probing scores	Samples will be obtained during the intervention and will be kept in -80oC until immunohistochemical analysis which will be carried out through study completion, 6-9 months
Primary	Baseline density of macrophage types in granulation tissue samples	two pockets (=6mm; BoP+) from each individual; Immunoblot analysis: cluster of differentiation(CD)68 and CD163; cell number / optic field (cells/mm2); each will be correlated with the change in probable pocket depth and bleeding on probing scores	Samples will be obtained during the intervention and will be kept in -80oC until immunohistochemical analysis which will be carried out through study completion, 6-9 months
Secondary	Change in macrophage and Th17-pathway related cytokine concentrations in saliva	MCP-1, -2, -3, -4, MDC, MIF, MIG, MIP-1a, IP-10, IL1ß, -4, -6, -10, -17A, -17F, -21, -22, -23, -25, -31, -33, IFN-?, sCD-40L, TNF-?, sCD163, TWEAK, BAFF, sST2 concentrations (pg/mL); will be correlated with the change in probable pocket depth and bleeding on probing scores	baseline, 2nd, 6th, 12th and 24th weeks following therapy; immunohistochemical analysis will be carried out through study completion, 6-9 months
Secondary	Change in macrophage and Th17-pathway related cytokine concentrations in gingival crevicular fluid (GCF)	MCP-1, -2, -3, -4, MDC, MIF, MIG, MIP-1a, IP-10, IL1ß, -4, -6, -10, -17A, -17F, -21, -22, -23, -25, -31, -33, IFN-?, sCD-40L, TNF-?, sCD163, TWEAK, BAFF, sST2 concentrations (pg/mL); will be correlated with the change in probable pocket depth and bleeding on probing scores	baseline, 2nd, 6th, 12th and 24th weeks following therapy; immunohistochemical analysis will be carried out when through study completion, 6-9 months
Secondary	Change in plaque index	Silness-Löe plaque index (scored as 0-3); full-mouth, 6 sites per tooth; will be monitored for oral health assessment during the healing period	baseline, 2nd, 6th, 12th and 24th weeks following therapy
Secondary	Change in clinical attachment level (CAL)	distance between the cement-enamel junction and pocket base (mm); full-mouth, 6 sites per tooth; will be correlated with pocket depth reduction	baseline, 2nd, 6th, 12th and 24th weeks following therapy
Secondary	Change in biofilm microbiota	DNA isolation and next generation sequencing: P. gingivalis, T. denticola, T. forsythia, P. intermedia, F. nucleatum and A. actinomycetemcomitans; bacterial count (log10 scale)	baseline, 2nd, 6th, 12th and 24th weeks following therapy; microbiological analysis will be carried out through clinical phase completion, 6-9 months
Secondary	Change in neutrophil-associated cytokines in saliva	MMP-2, MMP-7, MMP-8, active MMP-8, MMP-9, MMP-13, TIMP, myeloperoxidase, PMN elastase (IFMA and ELISA methods) concentrations (pg/mL) in saliva	baseline, 6th, 12th and 24th weeks following therapy
Secondary	Change in neutrophil-associated cytokines in and oral rinse	MMP-2, MMP-7, MMP-8, active MMP-8, MMP-9, MMP-13, TIMP, myeloperoxidase, PMN elastase (IFMA and ELISA methods) concentrations (pg/mL) in oral rinse samples	baseline, 6th, 12th and 24th weeks following therapy
Secondary	active MMP-8 point-of-care test results in oral rinse	Dichotomous aMMP-8 test results in oral rinse samples (according to the manufacturer, a concentration below 20 ng/mL gives a negative test result, otherwise positive - Periosafe (R) Dentognostics GmHb, Jena, Germany)	baseline, 6th, 12th and 24th weeks following therapy