Brief Summary

Periodontal disease is a chronic and progressive inflammatory disease in which the hard and soft tissues that support the teeth are damaged. It is caused by the interaction between harmful bacteria and the body's immune responses, and most periodontal tissues are damaged by the body's abnormal response to these microorganisms and their products. When bacteria enter the body, immune cells (neutrophils) produce reactive oxygen species (ROS) in a process called the "respiratory burst". These ROS damage cells, causing tissue destruction through a variety of mechanisms, including DNA damage, fat oxidation and protein damage. Studies have shown that neutrophils from individuals with periodontal disease produce more ROS than neutrophils from healthy individuals. High amounts of ROS lead to oxidative damage to gum tissue, periodontal ligament and alveolar bone. Oxidative stress occurs when antioxidants in the body are insufficient or when high levels of ROS are present. Therefore, disruption of the balance between oxidant and antioxidant activities is considered an important cause of oxidative damage in periodontal tissues. Parameters such as total antioxidant status (TAS), total oxidant status (TOS) and oxidative stress index (OSI) are used to determine oxidative stress. Furthermore, some enzymes such as arylesterase (ARE), heme oxygenase (HO) and nuclear factor erythroid 2-related factor 2 (NRF-2) are involved in defense mechanisms against oxidative stress. Many recent studies have shown a strong association between oxidative stress and periodontal disease.

Trial Health

On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment

participants targeted

Target at P50-P75 for all trials

Timeline

Completed

Started May 2023

Geographic Reach

1 country

1 active site

Status

completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

1.4 years study duration

Study Start

First participant enrolled

May 1, 2023

Completed

1 year until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 1, 2024

Completed

5 months until next milestone

Study Completion

Last participant's last visit for all outcomes

September 15, 2024

Completed

7 months until next milestone

First Submitted

Initial submission to the registry

April 22, 2025

Completed

1 month until next milestone

First Posted

Study publicly available on registry

May 22, 2025

Completed

Last Updated

May 22, 2025

Status Verified

May 1, 2025

Enrollment Period

1 year

First QC Date

April 22, 2025

Last Update Submit

May 15, 2025

Conditions

Periodontal Health Periodontitis Stage III

Keywords

total antioxidan statustotal oxidan statusoxidative stress indexarylesteraseheme oxygenasenuclear factor erythroid 2 related factor 2salivaserumstage III periodontitis

Outcome Measures

Primary Outcomes (6)

serum and saliva TAS (mmol Trolox Eq/L) levels
TAS concentrations were evaluated utilizing an innovative automated colorimetric assay, originally developed by Erel. The outcomes were reported as millimoles of Trolox equivalent per liter (mmol Trolox Eq/L). Total antioxidant levels are significantly lower in periodontitis patients compared to healthy individuals, suggesting increased oxidative stress associated with periodontal inflammation.
6 months
serum and saliva TOS (µmol H₂O₂ Eq/L) levels
TOS concentrations were determined through a distinct automated colorimetric technique, also described by Erel. Results were expressed as micromoles of hydrogen peroxide equivalent per liter (µmol H₂O₂ Eq/L). Compared to healthy controls, periodontitis patients show higher total oxidant levels, which may contribute to tissue destruction and disease progression.
6 months
serum and saliva OSI levels
TAS values (initially in mmol Trolox Eq/L) were converted to µmol Trolox Eq/L. OSI was then computed using the following formula: OSI = \[(TOS, µmol/L) / (TAS, µmol Trolox Eq/L)\] × 100. The oxidative stress index is significantly higher in periodontitis patients compared to healthy individuals, reflecting an imbalance between oxidants and antioxidants.
6 months
serum and saliva ARE (U/L) levels
Arylesterase activity was assessed using commercially available assay kits (Rel Assay Diagnostics, Turkey). For the measurement of arylesterase activity, phenylacetate was used as the substrate. The enzymatic activity was calculated based on the molar extinction coefficient of the phenol formed (1,310 M-¹cm-¹). One unit of arylesterase activity was defined as the amount of enzyme required to hydrolyze 1 µmol of phenol per minute under the assay conditions and was also expressed as U/L. Arylesterase activity is significantly decreased in periodontitis patients compared to healthy controls, suggesting impaired antioxidant enzyme function.
6 months
serum and saliva NRF-2 (ng/ml) levels
The level of NRF-2 was quantified using an enzyme-linked immunosorbent assay (ELISA) kit (BT lab.). In this assay, wells were pre-coated with human NRF-2-specific antibodies. Samples containing NRF2 were added to the wells, allowing target binding. Subsequently, a biotin-conjugated anti-NRF-2 antibody was applied, followed by streptavidin-horseradish peroxidase (HRP) conjugate. After washing to remove unbound components, a substrate solution was added, producing a colorimetric reaction proportional to the amount of NRF-2 present. The reaction was terminated by adding an acidic stop solution, and absorbance was measured at 450 nm. It is suggested that the reduced expression of NRF-2 in periodontitis patients, relative to healthy controls, contributes to increased oxidative stress and tissue damage.
6 months
serum and saliva HO-1(ng/ml) levels
The concentration of HO-1 was measured using an ELISA kit (BT Lab.) Wells were pre-coated with human HO-1-specific antibodies. Following the addition of samples, human HO-1 proteins bound to the immobilized antibodies. A biotinylated anti-HO-1 antibody and subsequently streptavidin-HRP conjugate were introduced. After removal of unbound components via washing, a substrate solution was added to initiate color development, which was proportional to the HO-1 concentration. The reaction was stopped using an acidic solution, and absorbance was recorded at 450 nm. Compared to healthy subjects, HO-1 is considered to be less expressed in periodontitis patients, potentially compromising antioxidant and anti-inflammatory defenses
6 months

Secondary Outcomes (5)

Gingival Index (GI)
6 months
Plaque Index (PI)
6 months
Bleeding on Probing Index (BoP)
6 months
Clinical Attachment Loss (CAL) (millimeter)
6 months
Pocket Depth (PD) (millimeter)
6 months

Study Arms (2)

stage III grade B periodontitis

Pocket deep ≤ 6 mm, clinical attachment loss ≥ 5 mm, tooth loss related to periodontitis ≤ 4, radiographic bone loss/age between 0.25-1 and periodontal tissue destruction compatible with biofilm accumulation.

Diagnostic Test: Serum Total Oxidant StatusDiagnostic Test: Salivary Total Oxidant StatusDiagnostic Test: Serum Total Antioxidant StatusDiagnostic Test: Salivary Total Antioxidant StatusDiagnostic Test: Serum Oxidative Stress IndexDiagnostic Test: Salivary Oxidative Stress IndexDiagnostic Test: Serum ArylesteraseDiagnostic Test: Salivary ArylesteraseDiagnostic Test: Serum Heme OxygenaseDiagnostic Test: Salivary Heme OxygenaseDiagnostic Test: Serum Nuclear Factor Erythroid 2 Related Factor 2Diagnostic Test: Salivary Nuclear Factor Erythroid 2 Related Factor 2Diagnostic Test: Gingival IndexDiagnostic Test: Plaque IndexDiagnostic Test: Bleeding on Probing IndexDiagnostic Test: Clinical Attachment LossDiagnostic Test: Pocket Deep

periodontally health

Pocket deep ≤ 3 mm, bleeding on probing index ≤ %10 and gingival index ≤ 1