Nitro-oxidative Stress in Periodontitis

NCT ID: NCT02127203

Last Updated: 2015-10-05

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

80 participants

Study Classification

OBSERVATIONAL

Study Start Date

2014-05-31

Study Completion Date

2015-10-31

Brief Summary

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Periodontitis is a chronic inflammatory disease whose etio-pathogencity is not fully understood yet. Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are involved in physiological and pathological processes. Nitro-oxidative stress has been implicated in Periodontitis.

The aim of this study is to assess the levels of ROS and RNS in serum and gingival crevicular fluid (GCF) samples taken from periodontitis (chronic and aggressive) patients and healthy controls. Subsequently, correlating these levels with the severity of periodontal disease.

Eighty subjects will be invited to participate in this study. Patients will be allocated into four groups (20 patients each). The biochemical parameters that will be investigated are Malondialdehyde (MDA) (using TBRSA assay) as a marker of oxidative stress and (NO- level using Griess reagent) as a marker of nitrosative stress.

Detailed Description

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Introduction:

Teeth and their supporting periodontal structures are of great importance in good oral health. Periodontitis is an inflammatory disease of the periodontium which affects the supporting tissues of the teeth. The disease is multifaceted and its etio-pathogenecity is still not fully understood and therefore the treatment of different types of periodontal disease can be very difficult. Numerous risk factors have been implicated in the disease process including risk determinants and risk indicators. Most recently, strong body of evidence has accumulated to support a role for reactive oxygen (ROS) and nitrogen species (RNS) either as trigger agents or more frequently, aggravators of the primary lesions in periodontitis.

Oxygen and nitrogen reactive species are involved in a large number of physiological and pathological processes. ROS generated by monocytes and neutrophyles during inflammation are important aggression factors in the periodontal tissues. ROS play an important role in activation of osteoclasts and in bone resorption.

Oxidative stress is a condition arising when there is a serious imbalance between the levels of free radicals in a cell and its antioxidant defenses in favor of the former. Thus, tissue damage can result when antioxidant systems are unable to counteract the free radicals actions efficiently. Inflammation when stimulated by bacterial pathogens, host cells release proinflammatory cytokines (IL-1α, IL-6, IL-8, and tumor necrosis factor-α) as part of immune response. These cytokines recruit polymorphonuclear cells (PMNs) that play a major role in the etiology of periodontal disease by producing proteolytic enzymes, such as elastase and O2 (molecular oxygen) by the oxidative burst.

In a recent study, Abou Sulaiman \& Shehadeh found that serum total antioxidant capacity (TAS) was lower in non-smokers Syrian patients with chronic periodontitis compared to healthy controls. Also, they reported that periodontal treatment restored TAS levels to normal levels similar to healthy controls.

The aim of this study is to assess the levels of ROS and RNS in serum and gingival crevicular fluid (GCF) samples taken from periodontitis patients (chronic and aggressive) and healthy controls. Subsequently, correlating these levels with severity of periodontal disease in Syrian patients.

Materials and methods:

A total of 80 subjects will be invited to participate in this study from the patients referred to the Department of Periodontology, Faculty of Dentistry, University of Damascus. The study has been approved by our local Review Board. Subjects will be recruited according to specific inclusion criteria after completion of medical and dental history questionnaires. Patients will sign a consent form after being advised about the nature of the study.

The selection of patients will be made according of the criteria approved by the 1999 international world workshop for a classification system of periodontal diseases and conditions using five clinical parameters and full mouth or panoramic radiographs for diagnosis.

Subjects will be allocated into four groups:

* Chronic Periodontitis group (ChP): comprise 20 patients aged \> 45 years and have presence of ≥2 non-adjacent sites per quadrant that were not first molars or incisors, with probing depth (PD) ≥5 mm, which bleed on gentle probing. The demonstrated radiographic bone loss ≥30% of the root length, patient with poor oral hygiene, the amount of accumulated plaque commensurate with the amount of clinical attachment level (CAL)
* Resistant Control group (R): comprise 20 age-sex matched patients who are \> 45 years exhibit no signs of periodontal disease as determined by the absence of the evidence of interproximal (CAL ≤ 1mm), PD \> 3 mm at any site, whole-mouth bleeding scores \<10% and have no clinical signs of gingival inflammation .
* Aggressive Periodontitis group (AgP): comprise 20 patients who are aged \< 35 years and diagnosed with rapid attachment loss with periodontal pocket depth (PD) \> 4 mm around at least three teeth other than the first molars and incisors. Rapid bone destruction (\>50%bone loss at diseased sites). Weak relationship between dental plaque and the severity of gingival inflammation.
* Young Control group (YC): comprise 20 age- and sex matched patients who are \< 35 years and exhibit no signs of periodontal disease.

Clinical measurements:

A standard periodontal probe will be used for recording periodontal indices at six sites per tooth. The examined clinical parameters include bleeding on probing (BOP), plaque index (PI), clinical attachment loss (CAL) and periodontal pocket depth (PPD) and gingival index (GI).

Collection of samples

Subjects will be asked to refrain from brushing within 1 hour of sampling. (GCF) samples will be obtained using standard paper strips (Periocol strips, Oraflow, NY, USA). 6 samples from each individual (mesiofacial, distopalatal) sites from each examined tooth (incisor, premolar and molar) in the maxilla (Chapple et al. 2002). Strips will be put in PBS Buffer solution for 30 minutes then extracted and stored under liquid nitrogen.

Venous blood samples will be collected from the antecubital fossa and stored in lithium heparin tubes and allowed to stand for 30 minutes before being centrifuged at 1000 ×g for 30 minutes, samples will be aliquoted into cryogenic vials and will be stored under liquid nitrogen.

Laboratory studies:

* TBARS assay (HPLC) will be used to assess the malondialdihyde levels as a marker of oxidative stress.
* Griess reagent to assess nitric oxide levels as a marker of nitrosative stress.

Conditions

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Chronic Periodontitis Aggressive Periodontitis

Study Design

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Observational Model Type

CASE_CONTROL

Study Time Perspective

CROSS_SECTIONAL

Study Groups

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Chronic Periodontitis group (ChP)

20 patients aged \> 45 years and have presence of ≥2 non-adjacent sites per quadrant that were not first molars or incisors, with probing depth (PD) ≥5 mm, which bleed on gentle probing. The demonstrated radiographic bone loss ≥30% of the root length, patient with poor oral hygiene, the amount of accumulated plaque commensurate with the amount of clinical attachment level (CAL)

No interventions assigned to this group

Resistant Control group (R)

20 age-sex matched patients who are \> 45 years exhibit no signs of periodontal disease as determined by the absence of the evidence of interproximal (CAL ≤ 1mm), PD \> 3 mm at any site, whole-mouth bleeding scores \<10% and have no clinical signs of gingival inflammation .

No interventions assigned to this group

Aggressive Periodontitis group (AgP)

20 patients who are aged \< 35 years and diagnosed with rapid attachment loss with periodontal pocket depth (PD) \> 4 mm around at least three teeth other than the first molars and incisors. Rapid bone destruction (\>50%bone loss at diseased sites). Weak relationship between dental plaque and the severity of gingival inflammation.

No interventions assigned to this group

Young Control group (YC)

20 age- and sex matched patients who are \< 35 years and exhibit no signs of periodontal disease.

No interventions assigned to this group

Eligibility Criteria

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Inclusion Criteria

* Patients of Syrian descent
* Systemically healthy
* Have at least 20 teeth

Exclusion Criteria

* Periodontal treatment during the last three months,
* History of major systemic diseases
* Consumption of anti oxidant supplements, antibiotics, anti inflammatory or any other drugs in the last three months
* Smoking
* Alcohol consumption
* Pregnant and lactating women.
Minimum Eligible Age

18 Years

Maximum Eligible Age

60 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Damascus University

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Abeer Alasadi, DDS

Role: PRINCIPAL_INVESTIGATOR

MSc student, Department of Periodontology, University of Damascus Dental School

Ali Abou Sulaiman, DDS MSc Phd

Role: STUDY_DIRECTOR

Senior Lecturer in Periodontics, University of Damascus Dental School, Damascus

Francoise Qarabit, BSc MSc PhD

Role: STUDY_DIRECTOR

Senior Lecturer in Chemistry, Department of Chemistry, Faculty of Sciences, University of Damascus, Baramkeh, Damascus, Syria

Locations

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Department of Periodontics, University of Damascus Dental School

Damascus, Rif-dimashq Governorate, Syria

Site Status

Countries

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Syria

References

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Abou Sulaiman AE, Shehadeh RM. Assessment of total antioxidant capacity and the use of vitamin C in the treatment of non-smokers with chronic periodontitis. J Periodontol. 2010 Nov;81(11):1547-54. doi: 10.1902/jop.2010.100173. Epub 2010 Jun 22.

Reference Type BACKGROUND
PMID: 20569170 (View on PubMed)

Armitage GC. Development of a classification system for periodontal diseases and conditions. Ann Periodontol. 1999 Dec;4(1):1-6. doi: 10.1902/annals.1999.4.1.1.

Reference Type BACKGROUND
PMID: 10863370 (View on PubMed)

Chapple IL, Matthews JB. The role of reactive oxygen and antioxidant species in periodontal tissue destruction. Periodontol 2000. 2007;43:160-232. doi: 10.1111/j.1600-0757.2006.00178.x. No abstract available.

Reference Type BACKGROUND
PMID: 17214840 (View on PubMed)

Halliwell B. Reactive oxygen species in living systems: source, biochemistry, and role in human disease. Am J Med. 1991 Sep 30;91(3C):14S-22S. doi: 10.1016/0002-9343(91)90279-7.

Reference Type BACKGROUND
PMID: 1928205 (View on PubMed)

Kinane DF. Causation and pathogenesis of periodontal disease. Periodontol 2000. 2001;25:8-20. doi: 10.1034/j.1600-0757.2001.22250102.x. No abstract available.

Reference Type BACKGROUND
PMID: 11155179 (View on PubMed)

Sies H. Oxidative stress: oxidants and antioxidants. Exp Physiol. 1997 Mar;82(2):291-5. doi: 10.1113/expphysiol.1997.sp004024.

Reference Type BACKGROUND
PMID: 9129943 (View on PubMed)

Wactawski-Wende J. Periodontal diseases and osteoporosis: association and mechanisms. Ann Periodontol. 2001 Dec;6(1):197-208. doi: 10.1902/annals.2001.6.1.197.

Reference Type BACKGROUND
PMID: 11887465 (View on PubMed)

Other Identifiers

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UDDS-Perio-03-2014

Identifier Type: -

Identifier Source: org_study_id

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