HALP Score, Blood-Based Inflammatory Indices, and Salivary MMP-8 in Periodontal Disease and Healing After Non-Surgical Therapy

The Relationship of HALP Score, Blood-Based Inflammatory Indices, and Salivary MMP-8 Levels With Periodontal Disease and Healing After Non-Surgical Periodontal Therapy

This observational clinical study aims to investigate the relationship between the HALP score (Hemoglobin × Albumin × Lymphocyte / Platelet), several blood-based inflammatory indices (including NLR, PLR, LMR, and SII), and salivary MMP-8 levels in individuals with periodontal health, gingivitis, and stage III/IV periodontitis. The study also evaluates how these biomarkers relate to healing following non-surgical periodontal therapy.

A total of 180 participants aged 18-65 years will be included: 50 healthy individuals, 50 patients with gingivitis, and 80 patients with stage III/IV periodontitis. All participants will undergo periodontal clinical examination and provide blood and saliva samples at baseline. Individuals in the gingivitis and periodontitis groups will receive standard non-surgical periodontal treatment (full-mouth debridement) and will return for a 3-month follow-up visit, where periodontal measurements will be repeated. In the periodontitis group, an additional blood sample will be collected at the 3-month follow-up visit.

The primary objective is to determine whether baseline HALP score, systemic inflammatory indices, and salivary MMP-8 levels differ between participants who show good versus poor healing after treatment. Secondary objective include comparing biomarker levels across periodontal status groups. The findings may contribute to early prediction of treatment response and personalized periodontal care.

Study Overview

• Status: Recruiting
• Conditions: Periodontitis; Periodontal Diseases; Gingivitis; Chronic
• Intervention / Treatment: Procedure: Non-surgical Periodontal Therapy

Detailed Description

Following baseline assessments, participants in the gingivitis and periodontitis groups will receive standard non-surgical periodontal therapy. Periodontal clinical measurements will be repeated at the 3-month follow-up visit in these groups. In accordance with the existing ethics committee approval and following further feasibility assessment, an additional blood sample will be collected at the 3-month follow-up visit exclusively from participants in the periodontitis group.

• Study Type: Observational
• Enrollment (Estimated): 180

Contacts and Locations

• Study Contact: Name: Ömer Faruk Okumuş, Assistant Professor; Phone Number: +905532140969; Email: okumus.omer24@gmail.com

Study Locations

• Turkey (Türkiye)
  • Erzincan
    • Merkez, Erzincan, Turkey (Türkiye), 24002
      • Recruiting
      • Erzincan Binali Yıldırım University Faculty of Dentistry
      • Contact: Ömer Faruk Okumuş, Assistant Professor; Phone Number: 05532140969; Email: okumus.omer24@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Adult individuals aged 18-65 years presenting to the periodontology clinic for routine examination or periodontal treatment. Participants will be assigned to healthy, gingivitis, or stage III/IV periodontitis groups based on periodontal diagnosis.

Description

Inclusion Criteria:

• Adults aged 18-65 years
• Ability to provide informed consent
• No systemic diseases or conditions affecting periodontal status
• For Healthy Group: Probing depth ≤3 mm, no attachment loss, no radiographic bone loss
• For Gingivitis Group: Gingival inflammation and bleeding on probing without attachment loss or bone loss
• For Periodontitis Group: Stage III or stage IV periodontitis according to 2018 classification
• No periodontal treatment within the past 6 months
• Willingness to attend follow-up visits

Exclusion Criteria:

• Systemic diseases influencing periodontal inflammation (e.g., diabetes, autoimmune disorders)
• Current pregnancy or lactation
• Use of antibiotics, anti-inflammatory medications, or immunosuppressive drugs within the last 3 months
• Smokers or individuals using tobacco products
• History of periodontal surgery in the last 6 months
• Presence of fewer than 20 natural teeth
• Any condition that may interfere with study participation or data reliability

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Periodontally Healthy Individuals; Participants with no clinical signs of gingival inflammation, probing depth ≤3 mm, no clinical attachment loss, and no radiographic bone loss. These individuals serve as the healthy control group.	Procedure: Non-surgical Periodontal Therapy; Standard full-mouth supra- and subgingival debridement performed in a single session, followed by oral hygiene instructions.
Gingivitis Patients; Participants with visible signs of gingival inflammation and bleeding on probing, but without clinical attachment loss or radiographic bone loss. These individuals will receive standard non-surgical periodontal therapy.	Procedure: Non-surgical Periodontal Therapy; Standard full-mouth supra- and subgingival debridement performed in a single session, followed by oral hygiene instructions.
Stage III/IV Periodontitis Patients; Participants diagnosed with stage III or stage IV periodontitis, characterized by clinical attachment loss, probing depth ≥5 mm, and radiographic bone loss. These individuals will receive standard non-surgical periodontal therapy and will be re-evaluated at 3 months.	Procedure: Non-surgical Periodontal Therapy; Standard full-mouth supra- and subgingival debridement performed in a single session, followed by oral hygiene instructions.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Differences in Baseline HALP Score Between Good and Poor Treatment Responders	Evaluation of whether baseline HALP score differs between good responders (>2 mm reduction in probing depth at sites ≥5 mm) and poor responders (≤2 mm reduction) following non-surgical periodontal therapy in periodontitis patients.	Baseline (T0) to 3 months after treatment (T2)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Differences in Baseline NLR Between Good and Poor Responders	Comparison of baseline neutrophil-to-lymphocyte ratio between good and poor responders in the periodontitis group.	Baseline (T0)
Differences in Baseline PLR Between Good and Poor Responders	Comparison of baseline platelet-to-lymphocyte ratio between good and poor responders in the periodontitis group.	Baseline (T0)
Differences in Baseline LMR Between Good and Poor Responders	Comparison of baseline lymphocyte-to-monocyte ratio between good and poor responders in the periodontitis group.	Baseline (T0)
Differences in Baseline SII Between Good and Poor Responders	Comparison of baseline systemic immune-inflammation index between good and poor responders in the periodontitis group.	Baseline (T0)
Differences in Baseline Salivary MMP-8 Between Good and Poor Responders	Comparison of baseline salivary MMP-8 levels between good and poor responders in the periodontitis group.	Baseline (T0)
Baseline HALP Score Differences Across Periodontal Status Groups	Comparison of HALP score among healthy, gingivitis, and stage III/IV periodontitis groups.	Baseline (T0)
Baseline NLR Differences Across Periodontal Status Groups	Comparison of neutrophil-to-lymphocyte ratio among the three periodontal groups.	Baseline (T0)
Baseline PLR Differences Across Periodontal Status Groups	Comparison of platelet-to-lymphocyte ratio among the three periodontal groups.	Baseline (T0)
Baseline LMR Differences Across Periodontal Status Groups	Comparison of lymphocyte-to-monocyte ratio among the three periodontal groups.	Baseline (T0)
Baseline SII Differences Across Periodontal Status Groups	Comparison of systemic immune-inflammation index among the three periodontal groups.	Baseline (T0)
Baseline Salivary MMP-8 Differences Across Periodontal Status Groups	Comparison of salivary MMP-8 among healthy, gingivitis, and periodontitis groups.	Baseline (T0)
Changes in Probing Depth After Non-Surgical Periodontal Therapy	Mean reduction in probing depth from baseline to 3 months in gingivitis and periodontitis patients.	Baseline (T0) to 3 months (T2)
Change in HALP Score After Non-Surgical Periodontal Therapy in Periodontitis Patients	Evaluation of the change in HALP score from baseline to 3 months after non-surgical periodontal therapy in patients with stage III/IV periodontitis.	Baseline (T0) to 3 months (T2)
Correlations Between Clinical Periodontal Parameters and Biomarker Levels	Assessment of correlations between probing depth, bleeding on probing, plaque index, clinical attachment level, and biomarkers including HALP score, NLR, PLR, LMR, SII, and salivary MMP-8.	Baseline (T0)

Collaborators and Investigators

• Sponsor: Ömer Faruk Okumuş
• Collaborators: Erzincan Binali Yildirim Universitesi

Study record dates

Study Major Dates

• Study Start (Actual): November 25, 2025
• Primary Completion (Estimated): November 25, 2026
• Study Completion (Estimated): November 25, 2026

Study Registration Dates

• First Submitted: November 27, 2025
• First Submitted That Met QC Criteria: December 16, 2025
• First Posted (Actual): December 31, 2025

Study Record Updates

• Last Update Posted (Actual): December 31, 2025
• Last Update Submitted That Met QC Criteria: December 16, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Organizing Pneumonia; Mouth Diseases; Stomatognathic Diseases; Immune System Diseases; Infections; Respiratory Tract Diseases; Lung Diseases; Bronchial Diseases; Lung Diseases, Obstructive; Gingival Diseases; Bronchiolitis Obliterans; Bronchiolitis; Bronchitis; Graft vs Host Disease; Bronchiolitis Obliterans Syndrome; Periodontitis; Periodontal Diseases; Gingivitis
• Other Study ID Numbers: EBYU-HALP-2025

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No