Assesment of Gingival Crevicular Fluid and Serum ErbB4/Neuregulin-4 Levels in Periodontal Disease and Health

Lead Sponsor

Abant Izzet Baysal University

Source

Abant Izzet Baysal University

Oversight Info

Has Dmc

Is Fda Regulated Drug

Is Fda Regulated Device

Brief Summary

This study aimed to investigate gingival crevicular fluid (GCF) and serum ErbB4 and Nrg4 levels in periodontal health and disease. A total of 80 individuals, 20 patients with stage II grade B periodontitis, 20 patients with stage III grade B periodontitis, 20 with gingivitis and 20 periodontally healthy individuals were included. Whole-mouth and site-specific clinical periodontal parameters including probing depth, clinical attachment level, bleeding on probing, gingival index, plaque index and papillar bleeding index were recorded. GCF and serum ErbB4 and Nrg4 levels were measured by enzyme-linked immunosorbent assay. Statistical analysis was performed by using non-parametric tests.

Detailed Description

A total of 80 individuals, comprising 20 patients with stage II grade B periodontitis (P1 Group), 20 patients with stage III grade B periodontitis (P2 Group), 20 patients with gingivitis (G Group), and 20 periodontally healthy controls (H Group) were involved in the study. The participants were classified into four groups depending on periodontal health status in accordance with the consensus reports of the 2017 World Workshop: 1. periodontally healthy (H) group: no interproximal attachment loss (AL), probing depth (PD) ≤3 mm, bleeding on probing (BOP) scores <10%; 2. gingivitis (G) group: no interproximal AL, PD ≤3 mm, and BOP ≥10%; 3. stage II grade B periodontitis (P1) group: 3 5 mm and CAL ≥ 5 mm in one or more sites of the 2 non-adjacent teeth in at least two quadrants of the mouth, full mouth BOP >10% and tooth loss due to periodontitis of ≤4 teeth. Inclusion criteria were as follows: 1. aged >18 years, 2. having at least 16 natural teeth (excluding third molar), 3. not having any diagnosed medical illness or drug intake that could affect the periodontal condition. Exclusion criteria were as follows: 1. The patients who had taken antibiotics, nonsteroidal antiinflammatory or any other drugs within the past 3 months, 2. received nonsurgical or surgical periodontal treatment, 3. a restorative and endodontic therapy requirement, 4. a removable partial denture and/or having orthodontic therapy 5. Current pregnancy or lactation, obesity, heavy smoking and having serum C reactive protein (CRP) > 3mg/L. All individuals were examined at baseline and four weeks after non-surgical periodontal treatment including, whole mouth probing depth (PD), CAL, presence of bleeding on probing (BOP), papillar bleeding index (PBI), gingival index (GI) and plaque index (PI) except the third molars. PD and CAL were measured at six sites per tooth using a manual periodontal probe. The non-surgical periodontal treatment for P1 and P2 groups included supra- and subgingival scaling, root planing and oral hygiene instructions. Subgingival scaling and root planing were performed under local anesthesia in two sessions within the 48-72 h. Gingivitis group had supra-and subgingival scaling, polishing and oral hygiene instructions. The treatment of gingivitis and periodontitis patients were performed by a periodontist (BM) using hand and ultrasonic instruments. All measurements were performed by the same calibrated examiner (BM). Gingival crevicular fluid (GCF) sampling GCF samples were obtained from four nonadjacent interproximal sites in two maxillar and two mandibular multi-rooted teeth by standardized filter paper strips. GCF samples were taken from four sites with GI <1, PD ≤ 3, PBI =0 and CAL =0 in the H group; from four sites with GI ≥2, PD ≤3, PBI >2 and CAL=0 in the G group; from four sites (deepest pockets 3 2 and 3 ≤CAL <5 mm in P1 group; and from four sites (deepest pockets PD ≥5) with GI ≥2, PBI >2 and CAL ≥5 mm in P2 group according to the baseline clinical measurements. Serum sampling Serum samples were taken following GCF sampling before the periodontal treatment. Six milliliters of venous blood were obtained by a standard venipuncture method and the serum was separated from blood by centrifugation at 1,500 g for 20 minutes. Biochemical Assays Levels of GCF ErbB4, Nrg4, IL-6, IL-10 and levels of serum ErbB4, Nrg4, nitric oxide synthase (NOS)2 and Arg1 were measured by the enzyme-linked immunosorbent assay (ELISA) using commercial kits according to the manufacturer's guidelines. Statistical Analysis All data analyses were performed using a statistical software package. Comparisons of clinical and biochemical parameters between the study groups were performed using the Kruskal- Wallis with Mann Whitney U test with Bonferroni correction method. The intragroup comparisons (at baseline and first month) were performed using Wilcoxon test for paired samples. Associations among levels of the GCF and serum biomarkers and clinical parameters were also examined using the Spearman rank correlation analysis.

Overall Status

Completed

Start Date

2018-04-02

Completion Date

2019-01-18

Primary Completion Date

2019-01-18

Phase

N/A

Study Type

Interventional

Primary Outcome

Measure	Time Frame
Biochemical parameters (ErbB4 and Nrg4)	Baseline and 4 weeks after treatment
Biochemical parameters (IL-6, IL-10, nitric oxide synthase (NOS) 2 and Arg1)	Baseline and 4 weeks after treatment

Secondary Outcome

Measure	Time Frame
Probing pocket depth	Baseline and 4 weeks after treatment
Clinical attachment loss	Baseline and 4 weeks after treatment
Gingival index	Baseline and 4 weeks after treatment
Plaque index	Baseline and 4 weeks after treatment
Bleeding on probing	Baseline and 4 weeks after treatment
Papillar bleeding index	Baseline and 4 weeks after treatment

Enrollment

Condition

Periodontitis

Intervention

Intervention Type

Other

Intervention Name

non surgical periodontal treatment

Description

SRP under local anaesthesia, in a total of 2 clinical visits. Oral hygiene instructions including the modified Bass technique and an appropriate interdental cleaning device with dental floss and interdental brush.

Arm Group Label

stage II grade B periodontitis

stage III grade B periodontitis

gingivitis

Intervention Type

Other

Intervention Name

Gingival crevicular fluid and serum collection

Description

GCF with filter paper using the intracrevicular method and serum collection

Arm Group Label

stage II grade B periodontitis

stage III grade B periodontitis

gingivitis

periodontally healthy

Eligibility

Criteria

Inclusion Criteria: - Aged >18 years, - Having at least 16 natural teeth (excluding third molar), - Not having any diagnosed medical illness or drug intake that could affect the periodontal condition. Exclusion Criteria: - Patients who had taken antibiotics, nonsteroidal antiinflammatory or any other drugs within the past 3 months, - Patients received nonsurgical or surgical periodontal treatment, - Patients who have a restorative and endodontic therapy requirement, - Having a removable partial denture and/or having orthodontic therapy, - Current pregnancy or lactation, - Obesity, - Heavy smoking and having serum CRP > 3mg/L .

Gender

All

Minimum Age

18 Years

Maximum Age

N/A

Healthy Volunteers

Accepts Healthy Volunteers

Overall Official

Last Name	Role	Affiliation
Sadiye Gunpinar, Asst. Prof.	Principal Investigator	Abant Izzet Baysal University

Location

Facility

Bolu Abant Izzet Baysal University
Bolu 14030 Turkey

Location Countries

Country

Turkey

Verification Date

2019-08-01

Lastchanged Date

N/A

Firstreceived Date

N/A

Responsible Party

Responsible Party Type

Principal Investigator

Investigator Affiliation

Abant Izzet Baysal University

Investigator Full Name

Sadiye Gunpinar

Investigator Title

Asst. Prof.

Keywords

periodontal disease

, gingival crevicular fluid

, macrophage

, ErbB-4

, neuregulin-4

Has Expanded Access

Condition Browse

Periodontitis

N/A

Reference

Citation

Papapanou PN, Sanz M, Buduneli N, Dietrich T, Feres M, Fine DH, Flemmig TF, Garcia R, Giannobile WV, Graziani F, Greenwell H, Herrera D, Kao RT, Kebschull M, Kinane DF, Kirkwood KL, Kocher T, Kornman KS, Kumar PS, Loos BG, Machtei E, Meng H, Mombelli A, Needleman I, Offenbacher S, Seymour GJ, Teles R, Tonetti MS. Periodontitis: Consensus report of workgroup 2 of the 2017 World Workshop on the Classification of Periodontal and Peri-Implant Diseases and Conditions. J Periodontol. 2018 Jun;89 Suppl 1:S173-S182. doi: 10.1002/JPER.17-0721.

PMID

29926951

Citation

G Caton J, Armitage G, Berglundh T, Chapple ILC, Jepsen S, S Kornman K, L Mealey B, Papapanou PN, Sanz M, S Tonetti M. A new classification scheme for periodontal and peri-implant diseases and conditions - Introduction and key changes from the 1999 classification. J Clin Periodontol. 2018 Jun;45 Suppl 20:S1-S8. doi: 10.1111/jcpe.12935.

PMID

29926489

Firstreceived Results Disposition Date

N/A

August 7, 2019

Last Update Posted

August 9, 2019

ClinicalTrials.gov processed this data on December 13, 2019

Conditions

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Interventions

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Study Phase

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In Phase 2 (Phase II) clinical trials, the study drug or treatment is given to a larger group of people (100-300) to see if it is effective and to further evaluate its safety.

In Phase 3 (Phase III) clinical trials, the study drug or treatment is given to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.

In Phase 4 (Phase IV) clinical trials, post marketing studies delineate additional information including the drug's risks, benefits, and optimal use.

These phases are defined by the Food and Drug Administration in the Code of Federal Regulations.

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