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CompletedNCT07765251Updated Aug 14, 2026

Angiogenesis in Periodontal Disease

An observational study in Gingivitis, sponsored by Inonu University. Completed at 1 site in Turkey (Türkiye). Open to participants aged 18 Years to 65 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-08-14.

Sponsored by Inonu University · Observational

Study type
Observational
Model
Case-control
Time perspective
Cross-sectional
Enrollment
114
Ages
18 Years to 65 Years
Sex
All
01

Study summary

Gum disease (gingivitis and periodontitis) is a common inflammatory condition affecting the tissues that support the teeth. Smoking is known to make gum disease worse and to affect blood vessel health in the gums. This study looks at two proteins, KLF2 and FBXW7, which are involved in blood vessel formation, to understand their role in gum disease and whether smoking changes their levels. Researchers measured these proteins, along with two other markers of inflammation and blood vessel activity (VEGF and NF-κB), in fluid collected from around the teeth and in saliva from healthy adults who were either smokers or non-smokers, with healthy gums, gingivitis, or periodontitis. The goal is to better understand how smoking and gum disease affect blood vessel-related proteins in the mouth.

Read the detailed description

Angiogenesis, the formation of new blood vessels, is considered an early host response involved in the progression of periodontal disease. KLF2 is a transcription factor that negatively regulates angiogenesis and endothelial activation, while FBXW7 contributes to vascular development and has been reported to modulate KLF2 expression. Smoking is a major modifiable risk factor for periodontal disease and is known to affect periodontal vascularity, although the underlying molecular mechanisms remain incompletely understood. This study evaluates the potential involvement of KLF2 and FBXW7, alongside the established angiogenic and inflammatory mediators VEGF and NF-κB, in periodontal disease pathogenesis, and examines whether smoking modifies their expression in gingival crevicular fluid and saliva.

02

Conditions studied

  • Gingivitis

Keywords

  • periodontitis
  • gingivitis
  • smoking
  • angiogenesis
03

Who can participate

Ages eligible
18 Years to 65 Years
Sexes eligible
All
Accepts healthy volunteers
Yes
Sampling method
Non-probability sample

Study population

Adults aged 18 to 65 years attending the periodontology clinic were enrolled and classified into 6 groups based on clinical periodontal parameters and smoking status according to the 2017 World Workshop classification: periodontal health, gingivitis, and periodontitis (Stage III Grade B). Exclusion criteria included any systemic disease, regular medication use, pregnancy or lactation, periodontal treatment within the past 6 months, antibiotic use within the past 6 months, and presence of prosthetic restorations on the teeth to be sampled. A total of 114 participants (19 per group; 56 males, 58 females) were included.

Eligibility criteria

Inclusion Criteria:

Inclusion criteria for the Healthy Control group:

  • presence of ≥ 20 teeth in the mouth
  • probing pocket depth (PPD) ≤ 3 mm
  • the percentage of bleeding sites for the whole mouth \< 10%,
  • on radiographic examination, a distance of ≤ 3 mm between the cemento-enamel junction and the alveolar bone crest in 95% of all teeth.

Inclusion criteria for the Gingivitis group were

  • presence of ≥ 20 teeth in the mouth
  • PPD ≤ 3 mm,

    -% of bleeding sites for the whole mouth ≥ 10%,

  • on radiographic examination, a distance of ≤ 3 mm between the cemento-enamel junction and the alveolar bone crest in 95% of all teeth.

Inclusion criteria for the Stage 3 Periodontitis group

  • presence of ≥ 15 teeth in the mouth
  • more than 30% of teeth affected by periodontal disease
  • affected teeth exhibiting probing depths of 6 mm or more
  • clinical attachment loss (CAL) of ≥ 5 mm,
  • vertical bone loss of 3 mm or more
  • class 2 or 3 furcation involvement
  • radiographic evidence of alveolar bone loss extending to the middle third and beyond (33%) in the relevant teeth

Exclusion Criteria:

  • presence of any systemic disease
  • regular use of any medication
  • pregnancy or lactation
  • periodontal treatment within the last 6 months
  • antibiotic use within the last 6 months
  • the presence of prosthetic restorations on the teeth to be sampled
04

Study design

Observational model
Case-control
Time perspective
Cross-sectional
Enrollment
114 participants (actual)
Patient registry
No

Groups and cohorts

  • Group H

    periodontally healthy and non smokers

  • Group G

    gingivitis and non-smokers

  • Group P

    periodontitis and non-smokers

  • Group S-H

    periodontally healthy and non smokers

  • Group S-G

    gingivitis and smokers

  • Group S-P

    periodontitis and non-smokers

05

What researchers measure

Primary outcomes

  1. GCF and Salivary VEGF, NF-κB, KLF2, and FBXW7 Protein Levels

    Total amounts and concentrations of VEGF, NF-κB, KLF2, and FBXW7 were measured by ELISA in gingival crevicular fluid (GCF) and unstimulated whole saliva samples, and compared across participants with periodontal health, gingivitis, and periodontitis, in both smokers and non-smokers.

    Time frame: March to September 2024

06

Study locations

1 site
  • Inonu University, Faculty of Dentistry, Deparment of Periodontology
    Malatya, 44100, Turkey (Türkiye)
07

References and documents

Publications

  • Afacan B, Ozturk VO, Pasali C, Bozkurt E, Kose T, Emingil G. Gingival crevicular fluid and salivary HIF-1alpha, VEGF, and TNF-alpha levels in periodontal health and disease. J Periodontol. 2019 Jul;90(7):788-797. doi: 10.1002/JPER.18-0412. Epub 2018 Dec 11. PubMed 30536725 ↗
  • Leite FRM, Nascimento GG, Scheutz F, Lopez R. Effect of Smoking on Periodontitis: A Systematic Review and Meta-regression. Am J Prev Med. 2018 Jun;54(6):831-841. doi: 10.1016/j.amepre.2018.02.014. Epub 2018 Apr 12. PubMed 29656920 ↗
  • Kawanami D, Mahabeleshwar GH, Lin Z, Atkins GB, Hamik A, Haldar SM, Maemura K, Lamanna JC, Jain MK. Kruppel-like factor 2 inhibits hypoxia-inducible factor 1alpha expression and function in the endothelium. J Biol Chem. 2009 Jul 31;284(31):20522-30. doi: 10.1074/jbc.M109.025346. Epub 2009 Jun 1. PubMed 19491109 ↗
  • Arabi A, Ullah K, Branca RM, Johansson J, Bandarra D, Haneklaus M, Fu J, Aries I, Nilsson P, Den Boer ML, Pokrovskaja K, Grander D, Xiao G, Rocha S, Lehtio J, Sangfelt O. Proteomic screen reveals Fbw7 as a modulator of the NF-kappaB pathway. Nat Commun. 2012;3:976. doi: 10.1038/ncomms1975. PubMed 22864569 ↗

Individual participant data

Plan to share: Yes — De-identified individual participant data will be shared, including participant age, sex, and clinical periodontal parameters (plaque index, gingival index, probing depth, clinical attachment level, bleeding on probing). Participants will be identified only by coded/numbered case report forms; no names, gender identity beyond biological sex, or other identifying information will be shared.

Supporting information: Study protocol, Sap

08

Registry details

Key details

Study ID
NCT07765251
Lead sponsor
Inonu University
Responsible party
Kubra Aral (Associate Professor, Inonu University) — Principal investigator
First posted
Aug 14, 2026
Start date
Mar 1, 2024
Primary completion
Sep 30, 2024
Completion
Sep 30, 2024
Last update
Aug 14, 2026

Study contacts

Kubra Aral, Phd
study director · Inonu University

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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