CompletedNCT00681564Updated Apr 17, 2014Results posted

Periodontal Infection and Endothelial Dysfunction

A Phase 3 interventional study of One-Stage Full-Mouth Disinfection and Periodontal care in Periodontitis, sponsored by Universidad del Valle, Colombia. Completed at 2 sites in Colombia. Open to participants aged 25 Years and older, including healthy volunteers. Per ClinicalTrials.gov, last updated 2014-04-17.

Sponsored by Universidad del Valle, Colombia · Phase 3, Interventional, and Basic science

Phase: Phase 3
Study type: Interventional
Enrollment: 102
Allocation: Randomized
Ages: 25 Years and older
Sex: All

Study summary

The purpose of this study is to determine the effect of periodontal therapy on endothelial function and other biomarkers of cardiovascular disease

Read the 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.

Conditions studied

Periodontitis

Browse trials for

Periodontitis 1,635

Keywords

Periodontitis
Oral health
Cardiovascular disease

In context

Periodontitis

1,635 studies on the registry are indexed under Periodontitis; 327 are open to participants now.

This study's enrollment of 102 is above the median of 45 across 1,191 interventional studies indexed under Periodontitis.

Browse Periodontitis studies →

Lead sponsor

Universidad del Valle, Colombia is the lead sponsor of 13 studies on the registry; none are open to participants now.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 25 Years and older
Sexes eligible: All
Accepts 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

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

Study design

Phase: Phase 3
Primary purpose: Basic science
Allocation: Randomized
Intervention model: Parallel assignment
Masking: Double (Investigator, Outcomes assessor)
Enrollment: 102 participants (actual)

Study arms

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)
Procedure: One-Stage Full-Mouth Disinfection
Active comparator
Periodontal care
Basic oral hygiene instructions Supragingival plaque removal
Procedure: Periodontal care

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

What researchers measure

Primary outcomes

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

Secondary outcomes

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
Total Cholesterol
Time frame: Baseline; 24 hours post periodontal therapy; 12 weeks post periodontal therapy
White Blood Cell Count
Time frame: Baseline; 24 hours post periodontal therapy; 12 weeks post periodontal therapy
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
LDL Cholesterol
Time frame: Baseline; 24 hours post periodontal therapy; 12 weeks post periodontal therapy
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
Intercellular Adhesion Molecule 1 (ICAM-1)
Time frame: 12 weeks post periodontal therapy
Vascular Cell Adhesion Molecule 1 (VCAM-1)
Time frame: 12 weeks post periodontal therapy
Myeloperoxidase (MPO)
Time frame: 12 weeks post periodontal therapy
Matrix Metalloproteinase-9 (MMP-9)
Time frame: 12 weeks post periodontal therapy
Tissue Plasminogen Activator Inhibitor-1 (tPAI-1)
Time frame: 12 weeks post periodontal therapy

Results

Posted Apr 1, 2014

Limitations and caveats

1. Patient recruitment take more time that previously expected, 2. Longer time than expected for the standardization for laboratory techniques, 3. Changes of the study personnel during patient recruitment and laboratory analysis of biological samples

Participant flow

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.

Participant flow — Overall Study
Milestone	Periodontal Intervention (Experimental)	Periodontal Prophylaxis (Active Comparator)
Started	47	55
Completed	41	47
Not completed	6	8
Withdrew: Lost to follow-up	6	6
Withdrew: Withdrawal by subject	0	1
Withdrew: Death	0	1

Outcome measures

PrimaryBrachial 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
Reported as:: Mean · Percentage of dilatation of brachial art

Brachial Artery Flow-mediated Dilation
Percentage of dilatation of brachial art	Periodontal Intervention (Experimental)	Periodontal Prophylaxis (Active Comparator)
Baseline	10.2 ± 7.3	10.3 ± 8.7
24 hours	13.1 ± 9.5	8.1 ± 7.8
12 weeks	11.2 ± 9.7	9.7 ± 8.5

Statistical analysis

Periodontal Intervention (Experimental) vs Periodontal Prophylaxis (Active Comparator) · Kruskal-Wallis · p = 0.98 (A P value of 0.05 was used as a cut-off for statistical significance.)Non-parametric test appropriate for the analysis of non-normally distributed data.
Periodontal Intervention (Experimental) vs Periodontal Prophylaxis (Active Comparator) · Kruskal-Wallis · p = 0.005 (A P value of 0.05 was used as a cut-off for statistical significance.)Non-parametric test appropriate for the analysis of non-normally distributed data.
Periodontal Intervention (Experimental) vs Periodontal Prophylaxis (Active Comparator) · Kruskal-Wallis · p = 0.43 (A P value of 0.05 was used as a cut-off for statistical significance.)Non-parametric test appropriate for the analysis of non-normally distributed data.

SecondaryHigh-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
Reported as:: Mean · mg/L

High-sensitivity C-Reactive Protein
mg/L	Periodontal Intervention (Experimental)	Periodontal Prophylaxis (Active Comparator)
Baseline	4.2 ± 7.5	3.1 ± 3.7
24 hours	4.9 ± 6.7	4.1 ± 4.6
12 weeks	3.3 ± 4.9	3.2 ± 3.8

SecondaryTotal Cholesterol

Time frame:: Baseline; 24 hours post periodontal therapy; 12 weeks post periodontal therapy
Reported as:: Mean · mg/dL

Total Cholesterol
mg/dL	Periodontal Intervention (Experimental)	Periodontal Prophylaxis (Active Comparator)
Baseline	197 ± 38.7	192.4 ± 33.8
24 hours	195.4 ± 40.9	186.9 ± 42.8
12 weeks	203.9 ± 35.6	200.6 ± 39.5

SecondaryWhite Blood Cell Count

Time frame:: Baseline; 24 hours post periodontal therapy; 12 weeks post periodontal therapy
Reported as:: Mean · cells/mm^3

White Blood Cell Count
cells/mm^3	Periodontal Intervention (Experimental)	Periodontal Prophylaxis (Active Comparator)
Baseline	6937 ± 2986	6380 ± 1682
24 hours	6198 ± 2601	6088 ± 2411
12 weeks	5464 ± 3160	5382 ± 2963

SecondarySubgingival 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
Reported as:: Number · participants

Subgingival Microbiota
participants	Periodontal Intervention (Experimental)	Periodontal Prophylaxis (Active Comparator)
Participants positive for Pg	31	42
Participants positive for Td	31	38
Participants positive for Tf	34	40
Participants positive for Pg, Tf and Td	25	37

SecondaryLDL Cholesterol

Time frame:: Baseline; 24 hours post periodontal therapy; 12 weeks post periodontal therapy
Reported as:: Mean · mg/dL

LDL Cholesterol
mg/dL	Periodontal Intervention (Experimental)	Periodontal Prophylaxis (Active Comparator)
Baseline	113.1 ± 37.6	106.4 ± 32.8
24 hours	111.3 ± 41.3	104.6 ± 33.9
12 weeks	119.9 ± 38.8	109.5 ± 42.8

SecondaryEndothelial 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
Reported as:: Mean · ng/ml

Endothelial Leukocyte Adhesion Molecule-1 (E-Selectin)
ng/ml	Periodontal Intervention (Experimental)	Periodontal Prophylaxis (Active Comparator)
Endothelial Leukocyte Adhesion Molecule-1 (E-Selectin)	44.8 ± 28.7	42.9 ± 22.2

SecondaryIntercellular Adhesion Molecule 1 (ICAM-1)

Time frame:: 12 weeks post periodontal therapy
Reported as:: Mean · ng/ml

Intercellular Adhesion Molecule 1 (ICAM-1)
ng/ml	Periodontal Intervention (Experimental)	Periodontal Prophylaxis (Active Comparator)
Intercellular Adhesion Molecule 1 (ICAM-1)	247.1 ± 196.7	235.4 ± 229.6

SecondaryVascular Cell Adhesion Molecule 1 (VCAM-1)

Time frame:: 12 weeks post periodontal therapy
Reported as:: Mean · ng/ml

Vascular Cell Adhesion Molecule 1 (VCAM-1)
ng/ml	Periodontal Intervention (Experimental)	Periodontal Prophylaxis (Active Comparator)
Vascular Cell Adhesion Molecule 1 (VCAM-1)	1601.6 ± 372.4	1588.1 ± 412.3

SecondaryMyeloperoxidase (MPO)

Time frame:: 12 weeks post periodontal therapy
Reported as:: Mean · ng/ml

Myeloperoxidase (MPO)
ng/ml	Periodontal Intervention (Experimental)	Periodontal Prophylaxis (Active Comparator)
Myeloperoxidase (MPO)	62.6 ± 60.9	83.8 ± 140.4

SecondaryMatrix Metalloproteinase-9 (MMP-9)

Time frame:: 12 weeks post periodontal therapy
Reported as:: Mean · ng/ml

Matrix Metalloproteinase-9 (MMP-9)
ng/ml	Periodontal Intervention (Experimental)	Periodontal Prophylaxis (Active Comparator)
Matrix Metalloproteinase-9 (MMP-9)	103.4 ± 58.5	110.5 ± 68.2

SecondaryTissue Plasminogen Activator Inhibitor-1 (tPAI-1)

Time frame:: 12 weeks post periodontal therapy
Reported as:: Mean · ng/ml

Tissue Plasminogen Activator Inhibitor-1 (tPAI-1)
ng/ml	Periodontal Intervention (Experimental)	Periodontal Prophylaxis (Active Comparator)
Tissue Plasminogen Activator Inhibitor-1 (tPAI-1)	116.1 ± 74.1	110.7 ± 66.4

Adverse events

Collected over One day after periodontal therapy. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Periodontal Intervention (Experimental)	—	0/47 (0%)	47/47 (100%)
Periodontal Prophylaxis (Active Comparator)	—	1/55 (1.8%)	31/55 (56.4%)

Most frequent serious events

Most frequent serious events
Event	Periodontal Intervention (Experimental)	Periodontal Prophylaxis (Active Comparator)
Motor vehicle traffic accidentSocial circumstances	0/47	1/55

Most frequent other events

Most frequent other events
Event	Periodontal Intervention (Experimental)	Periodontal Prophylaxis (Active Comparator)
SwellingSurgical and medical procedures	47/47	28/55
Gingival erythema or bleedingSurgical and medical procedures	46/47	24/55
Periodontal pain (low-intensity)Surgical and medical procedures	36/47	18/55

Baseline characteristics

Age, Continuous
Age, Continuous(years)	Periodontal Intervention (Experimental)	Periodontal Prophylaxis (Active Comparator)	Total
Mean	45.5 ± 9.4	45.5 ± 8.1	45.5 ± 6.9

Sex: Female, Male
Sex: Female, Male(Participants)	Periodontal Intervention (Experimental)	Periodontal Prophylaxis (Active Comparator)	Total
Female	24	30	54
Male	23	25	48

Race/Ethnicity, Customized
Race/Ethnicity, Customized(participants)	Periodontal Intervention (Experimental)	Periodontal Prophylaxis (Active Comparator)	Total
White	6	5	11
Black	5	5	10
Indian	0	3	3
Mixed ethnicity	36	42	78

Smoking status
Smoking status(participants)	Periodontal Intervention (Experimental)	Periodontal Prophylaxis (Active Comparator)	Total
Currently smoking	12	14	26
Never smoker	24	28	52
Former smoker	11	13	24

Formal education
Formal education(participants)	Periodontal Intervention (Experimental)	Periodontal Prophylaxis (Active Comparator)	Total
Elementary education (1 to 5 years)	14	17	31
Secondary education (6 to 11 years)	22	25	47
Higher education (12 or more years)	11	13	24

Family monthly income
Family monthly income(participants)	Periodontal Intervention (Experimental)	Periodontal Prophylaxis (Active Comparator)	Total
Less than $300 USD	19	23	42
≥ $300 and ≤ $600 USD	24	22	46
More than $600 USD	4	10	14

Medical insurance
Medical insurance(participants)	Periodontal Intervention (Experimental)	Periodontal Prophylaxis (Active Comparator)	Total
None	5	5	10
State-subsidized healthcare	30	34	64
Contributory regime (private insurance)	11	15	26
Prepaid medicine plan	1	1	2

Endothelium-dependent brachial artery flow-mediated dilatation
Endothelium-dependent brachial artery flow-mediated dilatation(Percentage of dilation)	Periodontal Intervention (Experimental)	Periodontal Prophylaxis (Active Comparator)	Total
Mean	9.9 ± 7.4	9.9 ± 8.5	9.9 ± 7.9

1 further baseline measures are reported on the registry.

Study locations

2 sites

Red de Salud de Ladera E.S.E. Servicio de Odontología
Cali, Valle, Colombia
Universidad del Valle, Facultad de Salud, Escuela de Odontología
Cali, Valle, Colombia

References and documents

Publications

Ramirez JH, Parra B, Gutierrez S, Arce RM, Jaramillo A, Ariza Y, Contreras A. Biomarkers of cardiovascular disease are increased in untreated chronic periodontitis: a case control study. Aust Dent J. 2014 Mar;59(1):29-36. doi: 10.1111/adj.12139. Epub 2014 Feb 4. Erratum In: Aust Dent J. 2015 Mar;60(1):135. PubMed 24495202 ↗
Ramirez JH, Arce RM, Contreras A. Periodontal treatment effects on endothelial function and cardiovascular disease biomarkers in subjects with chronic periodontitis: protocol for a randomized clinical trial. Trials. 2011 Feb 16;12:46. doi: 10.1186/1745-6215-12-46. PubMed 21324167 ↗

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Apr 17, 2014, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT00681564
Lead sponsor: Universidad del Valle, Colombia
Responsible party: Jorge Hernán Ramírez (principal investigator, Universidad del Valle, Colombia) — Principal investigator
First posted: May 21, 2008
Start date: May 2008
Primary completion: Mar 2011
Completion: Jan 2012
Results posted: Apr 1, 2014
Last update: Apr 17, 2014

Study contacts

Adolfo Contreras, DDS, MS, PhD

principal investigator · Universidad del Valle

Jorge H Ramirez, MD, MS

principal investigator · Universidad del Valle

Oversight

Data monitoring committee: Yes

View the source record on ClinicalTrials.gov ↗

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