Periodontitis
Conditions
Keywords
Periodontitis, Oral health, Cardiovascular disease
Brief summary
The purpose of this study is to determine the effect of periodontal therapy on endothelial function and other biomarkers of cardiovascular disease
Detailed description
Periodontitis is one of the most prevalent chronic diseases and a frequent cause of tooth loss. Accumulation of subgingival dental biofilm in susceptible individuals is associated with an inflammatory host response characterized by the production of Matrix Metalloproteinases, reduction in collagen synthesis, increase in cytokine gene expression, and apoptosis of gingival fibroblasts. Finally, inflammation leads to destruction of periodontal ligament, alveolar bone resorption, and chronic periodontitis. Periodontitis is associated with increased serum levels of inflammatory cytokines and acute phase reactants. Multiple case-control and cohort studies have suggested that periodontitis is an independent risk factor for cardiovascular events, diabetic end-organ damage, pregnancy complications and respiratory diseases. Recent interventional studies have found that periodontal therapy could increase endothelium-dependent brachial artery flow-mediated dilation. The purpose of this controlled clinical trial is to determine the effect of periodontal therapy on endothelial function in subjects with moderate to severe chronic periodontitis. Furthermore, the relationship between putative periodontal pathogens and endothelial function will be also evaluated.
Interventions
PROCEDUREOne-Stage Full-Mouth Disinfection
* Scaling and root planing, four quadrants in one session * Tongue brushing with a 1% chlorhexidine gel (1 minute) * Mouth rinsing with a 0.2% chlorhexidine solution for (2 minutes) * Subgingival chlorhexidine (1%) irrigation in all pockets * Twice daily rinsing with clorhexidine (1 minute) during fourteen days after the periodontal intervention * Basic oral hygiene instructions * Dental extractions will be performed at the end of patient followup (only in cases of teeth that could not be saved)
PROCEDUREPeriodontal care
* Basic oral hygiene instructions * Supragingival plaque removal
Sponsors
Universidad del Valle, Colombia
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
25 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Subjects must be 25 years of age or older * Three or more periodontal pockets with a probing depth (PD) \> 5mm * Have at least 20 natural teeth * Provide informed consent and willingness to cooperate with the study protocol
Exclusion criteria
* History of antibiotic use in the previous three months * Pregnant or lactating females * Treatment with antihypertensive, antilipemic, antiarrhythmic, and other cardiovascular drugs * Systemic diseases such as diabetes, HIV/AIDS, liver disease, chronic renal failure, tuberculosis, and autoimmune diseases * Previous history of cardiovascular disease: Acute myocardial infarct, stable angina, unstable angina, heart failure, atrial fibrillation, atrioventricular block, peripheral vascular disease, cerebrovascular accident * Patients who received periodontal treatment within the last 3 months * Patients who require antibiotic prophylaxis before examination or treatment * Patients with mental retardation and dementia
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Brachial Artery Flow-mediated Dilation | Baseline; 24 hours post periodontal therapy; 12 weeks post periodontal therapy | All the assessments of vascular function were performed in the morning, in a temperature controlled room, with participants required to fast for at least 8 hours. Flow-mediated, endothelium dependent vasodilatation of the brachial artery (FMD) was measured using the technique described by Celermajer et al. using the guidelines reported by Coretti et al. FMD was calculated as the percentage of change in the diameter of brachial artery measured 45-60 s after cuff release in relation to the baseline measure (FMD%). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Total Cholesterol | Baseline; 24 hours post periodontal therapy; 12 weeks post periodontal therapy | — |
| White Blood Cell Count | Baseline; 24 hours post periodontal therapy; 12 weeks post periodontal therapy | — |
| Subgingival Microbiota | 12 weeks post-periodontal therapy | Polymerase chain reaction (PCR) was used for detection of the three red-complex periodontal pathogens in periodontal pockets: Porphyromonas gingivalis (Pg), Treponema denticola (Td) and Tannerella forsythia (Tf). |
| LDL Cholesterol | Baseline; 24 hours post periodontal therapy; 12 weeks post periodontal therapy | — |
| Endothelial Leukocyte Adhesion Molecule-1 (E-Selectin) | 12 weeks post periodontal therapy | Multiplexed immuno-cytometric assay for the simultaneous measurement of MMP-9, MPO, tPAI-1, E-Selectin, ICAM-1, and VCAM-1 in serum samples (Milliplex® MAP kit, Human Cardiovascular Disease Panel 1, Millipore®). Luminex® 200™ IS Total System and xPONENT software were used for data acquisition and analysis. |
| High-sensitivity C-Reactive Protein | Baseline; 24 hours post periodontal therapy; 12 weeks post periodontal therapy | The fasting plasma hs-CRP concentrations was evaluated using a quantitative solid-phase, chemiluminescent immunometric assay (Immulite 1000, Siemens). |
| Vascular Cell Adhesion Molecule 1 (VCAM-1) | 12 weeks post periodontal therapy | — |
| Myeloperoxidase (MPO) | 12 weeks post periodontal therapy | — |
| Matrix Metalloproteinase-9 (MMP-9) | 12 weeks post periodontal therapy | — |
| Tissue Plasminogen Activator Inhibitor-1 (tPAI-1) | 12 weeks post periodontal therapy | — |
| Intercellular Adhesion Molecule 1 (ICAM-1) | 12 weeks post periodontal therapy | — |
Countries
Colombia
Participant flow
Recruitment details
rom April 2008 to March 2011 three hundred and six subjects were assessed for eligibility to participate in this randomized clinical trial. One hundred and two patients were randomized to the control (n=55) and treatment group (n=47). At 12 weeks of follow-up, 47 patients (control group) and 41 patients (treatment group) completed the study.
Pre-assignment details
Two hundred and four patients were excluded from this study for the following reasons: no fulfillment of inclusion criteria (n=183), refusal to participate (n=4), not assistance to study appointments (n=15), and another reasons (n=2).
Participants by arm
| Arm | Count |
|---|---|
| Periodontal Intervention (Experimental) One-Stage Full-Mouth Disinfection: - Scaling and root planing, four quadrants in one session
* Tongue brushing with a 1% chlorhexidine gel (1 minute)
* Mouth rinsing with a 0.2% chlorhexidine solution for (2 minutes)
* Subgingival chlorhexidine (1%) irrigation in all pockets
* Twice daily rinsing with clorhexidine (1 minute) during fourteen days after the periodontal intervention
* Basic oral hygiene instructions
* Dental extractions will be performed at the end of patient followup (only in cases of teeth that could not be saved) | 47 |
| Periodontal Prophylaxis (Active Comparator) Periodontal care: - Basic oral hygiene instructions
\- Supragingival plaque removal | 55 |
| Total | 102 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 0 | 1 |
| Overall Study | Lost to Follow-up | 6 | 6 |
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Periodontal Intervention (Experimental) | Periodontal Prophylaxis (Active Comparator) | Total |
|---|---|---|---|
| Age, Continuous | 45.5 years STANDARD_DEVIATION 9.4 | 45.5 years STANDARD_DEVIATION 8.1 | 45.5 years STANDARD_DEVIATION 6.9 |
| Endothelium-dependent brachial artery flow-mediated dilatation | 9.9 Percentage of dilation STANDARD_DEVIATION 7.4 | 9.9 Percentage of dilation STANDARD_DEVIATION 8.5 | 9.9 Percentage of dilation STANDARD_DEVIATION 7.9 |
| Family monthly income ≥ $300 and ≤ $600 USD | 24 participants | 22 participants | 46 participants |
| Family monthly income Less than $300 USD | 19 participants | 23 participants | 42 participants |
| Family monthly income More than $600 USD | 4 participants | 10 participants | 14 participants |
| Formal education Elementary education (1 to 5 years) | 14 participants | 17 participants | 31 participants |
| Formal education Higher education (12 or more years) | 11 participants | 13 participants | 24 participants |
| Formal education Secondary education (6 to 11 years) | 22 participants | 25 participants | 47 participants |
| Medical insurance Contributory regime (private insurance) | 11 participants | 15 participants | 26 participants |
| Medical insurance None | 5 participants | 5 participants | 10 participants |
| Medical insurance Prepaid medicine plan | 1 participants | 1 participants | 2 participants |
| Medical insurance State-subsidized healthcare | 30 participants | 34 participants | 64 participants |
| Race/Ethnicity, Customized Black | 5 participants | 5 participants | 10 participants |
| Race/Ethnicity, Customized Indian | 0 participants | 3 participants | 3 participants |
| Race/Ethnicity, Customized Mixed ethnicity | 36 participants | 42 participants | 78 participants |
| Race/Ethnicity, Customized White | 6 participants | 5 participants | 11 participants |
| Serum C-reactive protein (CRP) | 4 mg/L STANDARD_DEVIATION 7 | 3.1 mg/L STANDARD_DEVIATION 3.6 | 3.6 mg/L STANDARD_DEVIATION 5.4 |
| Sex: Female, Male Female | 24 Participants | 30 Participants | 54 Participants |
| Sex: Female, Male Male | 23 Participants | 25 Participants | 48 Participants |
| Smoking status Currently smoking | 12 participants | 14 participants | 26 participants |
| Smoking status Former smoker | 11 participants | 13 participants | 24 participants |
| Smoking status Never smoker | 24 participants | 28 participants | 52 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 47 / 47 | 31 / 55 |
| serious Total, serious adverse events | 0 / 47 | 1 / 55 |
Outcome results
Primary
Brachial Artery Flow-mediated Dilation
All the assessments of vascular function were performed in the morning, in a temperature controlled room, with participants required to fast for at least 8 hours. Flow-mediated, endothelium dependent vasodilatation of the brachial artery (FMD) was measured using the technique described by Celermajer et al. using the guidelines reported by Coretti et al. FMD was calculated as the percentage of change in the diameter of brachial artery measured 45-60 s after cuff release in relation to the baseline measure (FMD%).
Time frame: Baseline; 24 hours post periodontal therapy; 12 weeks post periodontal therapy
Population: The primary outcome (difference on endothelium-dependent brachial artery FMD at baseline and three months after randomization) and the secondary outcome (hs-CRP, glucose, blood lipid profile and cardiovascular biomarkers) were analyzed using kruskal-wallis and unpaired t test depending on the distribution of the variables.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Periodontal Intervention (Experimental) | Brachial Artery Flow-mediated Dilation | Baseline | 10.2 Percentage of dilatation of brachial art | Standard Deviation 7.3 |
| Periodontal Intervention (Experimental) | Brachial Artery Flow-mediated Dilation | 24 hours | 13.1 Percentage of dilatation of brachial art | Standard Deviation 9.5 |
| Periodontal Intervention (Experimental) | Brachial Artery Flow-mediated Dilation | 12 weeks | 11.2 Percentage of dilatation of brachial art | Standard Deviation 9.7 |
| Periodontal Prophylaxis (Active Comparator) | Brachial Artery Flow-mediated Dilation | Baseline | 10.3 Percentage of dilatation of brachial art | Standard Deviation 8.7 |
| Periodontal Prophylaxis (Active Comparator) | Brachial Artery Flow-mediated Dilation | 24 hours | 8.1 Percentage of dilatation of brachial art | Standard Deviation 7.8 |
| Periodontal Prophylaxis (Active Comparator) | Brachial Artery Flow-mediated Dilation | 12 weeks | 9.7 Percentage of dilatation of brachial art | Standard Deviation 8.5 |
Comparison: Analyzed variable: Brachial Artery Flow-mediated Dilation (baseline). Note: data analysis of patients who completed the study protocol (n=86). Intention-to-treat analysis analysis was not used because its application for the evaluation of continuous data would imply imputing missing data for patients lost to follow-up. Mean and standard deviation of flow-mediated dilatation, including data from all patients randomized in this study, is reported in the field of baseline characteristics.p-value: 0.98Kruskal-Wallis
Comparison: Analyzed variable: Brachial Artery Flow-mediated Dilation (24 hours).p-value: 0.005Kruskal-Wallis
Comparison: Statistical analysis: Brachial Artery Flow-mediated Dilation (12 weeks). Intention-to-treat analysis was not used because input of values for patients lost at follow-up will artificially amplify the precision of outcome measures.~Higgins JPT, Deeks JJ, Altman DG (editors). Chapter 16: Special topics in statistics. In: Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions. Version 5.0.1. The Cochrane Collaboration, 2008. www.cochrane-handbook.org.p-value: 0.43Kruskal-Wallis
Secondary
Endothelial Leukocyte Adhesion Molecule-1 (E-Selectin)
Multiplexed immuno-cytometric assay for the simultaneous measurement of MMP-9, MPO, tPAI-1, E-Selectin, ICAM-1, and VCAM-1 in serum samples (Milliplex® MAP kit, Human Cardiovascular Disease Panel 1, Millipore®). Luminex® 200™ IS Total System and xPONENT software were used for data acquisition and analysis.
Time frame: 12 weeks post periodontal therapy
Population: Explanation of missing data in the intervention group: Blood samples obtained from two patients randomized to the periodontal intervention group were not suitable for the Luminex analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Periodontal Intervention (Experimental) | Endothelial Leukocyte Adhesion Molecule-1 (E-Selectin) | 44.8 ng/ml | Standard Deviation 28.7 |
| Periodontal Prophylaxis (Active Comparator) | Endothelial Leukocyte Adhesion Molecule-1 (E-Selectin) | 42.9 ng/ml | Standard Deviation 22.2 |
Secondary
High-sensitivity C-Reactive Protein
The fasting plasma hs-CRP concentrations was evaluated using a quantitative solid-phase, chemiluminescent immunometric assay (Immulite 1000, Siemens).
Time frame: Baseline; 24 hours post periodontal therapy; 12 weeks post periodontal therapy
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Periodontal Intervention (Experimental) | High-sensitivity C-Reactive Protein | Baseline | 4.2 mg/L | Standard Deviation 7.5 |
| Periodontal Intervention (Experimental) | High-sensitivity C-Reactive Protein | 24 hours | 4.9 mg/L | Standard Deviation 6.7 |
| Periodontal Intervention (Experimental) | High-sensitivity C-Reactive Protein | 12 weeks | 3.3 mg/L | Standard Deviation 4.9 |
| Periodontal Prophylaxis (Active Comparator) | High-sensitivity C-Reactive Protein | Baseline | 3.1 mg/L | Standard Deviation 3.7 |
| Periodontal Prophylaxis (Active Comparator) | High-sensitivity C-Reactive Protein | 24 hours | 4.1 mg/L | Standard Deviation 4.6 |
| Periodontal Prophylaxis (Active Comparator) | High-sensitivity C-Reactive Protein | 12 weeks | 3.2 mg/L | Standard Deviation 3.8 |
Secondary
Intercellular Adhesion Molecule 1 (ICAM-1)
Time frame: 12 weeks post periodontal therapy
Population: Explanation of missing data in the intervention group: Blood samples obtained from two patients randomized to the periodontal intervention group were not suitable for the Luminex analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Periodontal Intervention (Experimental) | Intercellular Adhesion Molecule 1 (ICAM-1) | 247.1 ng/ml | Standard Deviation 196.7 |
| Periodontal Prophylaxis (Active Comparator) | Intercellular Adhesion Molecule 1 (ICAM-1) | 235.4 ng/ml | Standard Deviation 229.6 |
Secondary
LDL Cholesterol
Time frame: Baseline; 24 hours post periodontal therapy; 12 weeks post periodontal therapy
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Periodontal Intervention (Experimental) | LDL Cholesterol | Baseline | 113.1 mg/dL | Standard Deviation 37.6 |
| Periodontal Intervention (Experimental) | LDL Cholesterol | 24 hours | 111.3 mg/dL | Standard Deviation 41.3 |
| Periodontal Intervention (Experimental) | LDL Cholesterol | 12 weeks | 119.9 mg/dL | Standard Deviation 38.8 |
| Periodontal Prophylaxis (Active Comparator) | LDL Cholesterol | Baseline | 106.4 mg/dL | Standard Deviation 32.8 |
| Periodontal Prophylaxis (Active Comparator) | LDL Cholesterol | 24 hours | 104.6 mg/dL | Standard Deviation 33.9 |
| Periodontal Prophylaxis (Active Comparator) | LDL Cholesterol | 12 weeks | 109.5 mg/dL | Standard Deviation 42.8 |
Secondary
Matrix Metalloproteinase-9 (MMP-9)
Time frame: 12 weeks post periodontal therapy
Population: Explanation of missing data in the intervention group: Blood samples obtained from two patients randomized to the periodontal intervention group were not suitable for the Luminex analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Periodontal Intervention (Experimental) | Matrix Metalloproteinase-9 (MMP-9) | 103.4 ng/ml | Standard Deviation 58.5 |
| Periodontal Prophylaxis (Active Comparator) | Matrix Metalloproteinase-9 (MMP-9) | 110.5 ng/ml | Standard Deviation 68.2 |
Secondary
Myeloperoxidase (MPO)
Time frame: 12 weeks post periodontal therapy
Population: Explanation of missing data in the intervention group: Blood samples obtained from two patients randomized to the periodontal intervention group were not suitable for the Luminex analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Periodontal Intervention (Experimental) | Myeloperoxidase (MPO) | 62.6 ng/ml | Standard Deviation 60.9 |
| Periodontal Prophylaxis (Active Comparator) | Myeloperoxidase (MPO) | 83.8 ng/ml | Standard Deviation 140.4 |
Secondary
Subgingival Microbiota
Polymerase chain reaction (PCR) was used for detection of the three red-complex periodontal pathogens in periodontal pockets: Porphyromonas gingivalis (Pg), Treponema denticola (Td) and Tannerella forsythia (Tf).
Time frame: 12 weeks post-periodontal therapy
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Periodontal Intervention (Experimental) | Subgingival Microbiota | Participants positive for Pg | 31 participants |
| Periodontal Intervention (Experimental) | Subgingival Microbiota | Participants positive for Td | 31 participants |
| Periodontal Intervention (Experimental) | Subgingival Microbiota | Participants positive for Tf | 34 participants |
| Periodontal Intervention (Experimental) | Subgingival Microbiota | Participants positive for Pg, Tf and Td | 25 participants |
| Periodontal Prophylaxis (Active Comparator) | Subgingival Microbiota | Participants positive for Pg, Tf and Td | 37 participants |
| Periodontal Prophylaxis (Active Comparator) | Subgingival Microbiota | Participants positive for Pg | 42 participants |
| Periodontal Prophylaxis (Active Comparator) | Subgingival Microbiota | Participants positive for Tf | 40 participants |
| Periodontal Prophylaxis (Active Comparator) | Subgingival Microbiota | Participants positive for Td | 38 participants |
Secondary
Tissue Plasminogen Activator Inhibitor-1 (tPAI-1)
Time frame: 12 weeks post periodontal therapy
Population: Explanation of missing data in the intervention group: Blood samples obtained from two patients randomized to the periodontal intervention group were not suitable for the Luminex analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Periodontal Intervention (Experimental) | Tissue Plasminogen Activator Inhibitor-1 (tPAI-1) | 116.1 ng/ml | Standard Deviation 74.1 |
| Periodontal Prophylaxis (Active Comparator) | Tissue Plasminogen Activator Inhibitor-1 (tPAI-1) | 110.7 ng/ml | Standard Deviation 66.4 |
Secondary
Total Cholesterol
Time frame: Baseline; 24 hours post periodontal therapy; 12 weeks post periodontal therapy
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Periodontal Intervention (Experimental) | Total Cholesterol | Baseline | 197 mg/dL | Standard Deviation 38.7 |
| Periodontal Intervention (Experimental) | Total Cholesterol | 24 hours | 195.4 mg/dL | Standard Deviation 40.9 |
| Periodontal Intervention (Experimental) | Total Cholesterol | 12 weeks | 203.9 mg/dL | Standard Deviation 35.6 |
| Periodontal Prophylaxis (Active Comparator) | Total Cholesterol | Baseline | 192.4 mg/dL | Standard Deviation 33.8 |
| Periodontal Prophylaxis (Active Comparator) | Total Cholesterol | 24 hours | 186.9 mg/dL | Standard Deviation 42.8 |
| Periodontal Prophylaxis (Active Comparator) | Total Cholesterol | 12 weeks | 200.6 mg/dL | Standard Deviation 39.5 |
Secondary
Vascular Cell Adhesion Molecule 1 (VCAM-1)
Time frame: 12 weeks post periodontal therapy
Population: Explanation of missing data in the intervention group: Blood samples obtained from two patients randomized to the periodontal intervention group were not suitable for the Luminex analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Periodontal Intervention (Experimental) | Vascular Cell Adhesion Molecule 1 (VCAM-1) | 1601.6 ng/ml | Standard Deviation 372.4 |
| Periodontal Prophylaxis (Active Comparator) | Vascular Cell Adhesion Molecule 1 (VCAM-1) | 1588.1 ng/ml | Standard Deviation 412.3 |
Secondary
White Blood Cell Count
Time frame: Baseline; 24 hours post periodontal therapy; 12 weeks post periodontal therapy
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Periodontal Intervention (Experimental) | White Blood Cell Count | Baseline | 6937 cells/mm^3 | Standard Deviation 2986 |
| Periodontal Intervention (Experimental) | White Blood Cell Count | 24 hours | 6198 cells/mm^3 | Standard Deviation 2601 |
| Periodontal Intervention (Experimental) | White Blood Cell Count | 12 weeks | 5464 cells/mm^3 | Standard Deviation 3160 |
| Periodontal Prophylaxis (Active Comparator) | White Blood Cell Count | Baseline | 6380 cells/mm^3 | Standard Deviation 1682 |
| Periodontal Prophylaxis (Active Comparator) | White Blood Cell Count | 24 hours | 6088 cells/mm^3 | Standard Deviation 2411 |
| Periodontal Prophylaxis (Active Comparator) | White Blood Cell Count | 12 weeks | 5382 cells/mm^3 | Standard Deviation 2963 |