Expression of Epithelial-Mesenchymal Transition Associated Markers in Peri-implant Tissues

NCT05832541 | Recruiting

• 1 other identifier: 535622
• Study Type: observational
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

Peri-implantitis is an inflammation of bacterial etiology characterized by inflammation of mucous membranes and bone loss around the dental implant. A specific dental plaque bacteria could stimulate host cells, including the junctional epithelium, to secrete a range of pro-inflammatory cytokines involved in initiating the epithelial-mesenchymal transition (EMT) process. EMT has been described as the transdifferentiation of epithelial cells into motile mesenchymal cells. Moreover, cytokines and bacterial products have been highlighted as EMT-predisposing factors. The EMT process could render epithelial cells to lose their cell-cell adhesion and cell polarity that lend these cells to lose their function as an integrated epithelial barrier. E-cadherin is a calcium-dependent cell adhesion molecule that establishes cell-cell adhesion that plays a critical role in maintaining a barrier function in the human epithelium, including gingiva. The loss of E-cadherin is one of the most common biological indicators for EMT. In contrast, vimentin is an intermediate filament expressed in mesenchymal cells and is a canonical marker for EMT, which also promotes cell motility and an invasive phenotype. It is largely reported that EMT is regulated by various transcriptional factors such as Snail Family Transcriptional Repressor SNAIL1 and SNAIL2, zinc-finger E-box-binding (ZEB)1 and ZEB2 and TWIST transcription factors that suppress epithelial marker genes, and activate genes related with the mesenchymal phenotype. Recently, in vivo study has investigated the level of EMT markers in the gingival tissues of periodontitis patients. It was found that the expression of E-cadherin was downregulated while vimentin expression was upregulated. Despite the similarities and differences between the pathogenesis of periodontal and peri-implant diseases, the role of dental biofilm in the etiopathogenesis of the aforementioned diseases was studied largely. While it is now accepted that EMT may potentially play a role in periodontal disease pathogenicity, the possible role of EMT in the disintegration of the peri-implant epithelial barrier and the pathogenesis of peri-implant disease has not yet been investigated.

Conditions

Peri-implantitis

Keywords

Peri-implantitis; Peri-implant diseases; Epithelial-mesenchymal transition; E-cadherin; Vimentin

Outcome Measures

Primary Outcomes (3)

• Peri-implant probing pocket depth (PPD)

  PPD is the distance (in mm) measured from the Peri-implant mucosal margin to the base of the peri-implant sulcus/ pocket measured by using a periodontal probe, recorded at six sites per implant namely; mesio-facial, mid-facial, disto-facial, mesio-oral, mid-oral and disto-oral.

  Measured at baseline just before performing peri-implant tissue harvesting.

• Radiographic bone level (RBL)

  RBL is the distance (in mm) measured by periapical digital radiograph using the long-cone parallel technique from the implant platform to the radiographic bone level.

  Measured at baseline just before performing peri-implant tissue harvesting.

• Immunohistochemical expression of EMT-related markers

  Immunohistochemical expressions of two EMT-related markers (E-cadherin and vimentin) in peri-implant soft tissue samples collected from patients with peri-implantitis and healthy peri-implant tissue will be measured.

  Measured at baseline

Secondary Outcomes (2)

• Immunohistochemical expression EMT transcriptional factor

  Measured at baseline

• Bleeding on probing (BOP)

  Measured at baseline just before performing peri-implant tissue harvesting.

Study Arms (2)

Test group (peri-implantitis)

peri-implant tissue specimen will be taken after identification of diseased interproximal implant sites. Following local anesthesia specimen will be taken either by supracrestal incision to remove all diseased soft tissue surrounding the implant or by making 2 parallel incisions, 4 mm apart, with a 15C scalpel blade through the soft tissue until bone contact would be achieved. The 2 incisions will be connected with a perpendicular incision that will be placed at a distance of 4 mm from the proximal surface of implant. The biopsies, including the entire supracrestal soft tissue portion of the diseased site, will be carefully retrieved and prepared for histopathological and immunohistochemical analysis

Control group (clinically healthy)

tissue sample for control group will be collected from patients undergoing implant surgery. After local anesthesia, a crystal incision will be performed, and a full-thickness flap will be elevated. Following the osteotomy, one or more implants of 4.5-5.0 mm in diameter will be placed. A narrow diameter healing abutment will be screwed in with an insertion torque \> 20 NM., and flaps will be repositioned and sutured to obtain optimal adaptation of the mucosa to the titanium abutment. Sample harvesting will be done after 2 months of healing using circular punch of 4.5-5.0 mm diameter or performing a circular incision by surgical blade by which a 1.5 mm thick collar of peri-implant soft tissue will be harvested and prepared for histopathological and immunohistochemical analysis. A new 4.5-5.0 mm-wide smooth-surfaced healing abutment will be connected to the implant directly after the biopsy sampling.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

The participants of this study will be selected from the patients' pool who will attend private clinics in Karbala and nearby governorates. The target population will be those who seek dental implant therapy. The control group will involve those who intended for replacing their missing teeth by dental implants. On the other hand, the test group will involve those diagnosed with peri-implantitis and need surgical intervention during follow-up visits

You may qualify if:

• For test group: adult patient age ≥18 years old presented having at least one dental implant with the following criteria for test group 1: (a) be in function for \>12 months; (b) clinically diagnosed as peri-implantitis with probing pocket depth ≥ 6 mm, bleeding on probing and/or suppuration; (c) presence of radiographic bone loss when compared to previous radiographs or with bone loss ≥ 3 mm apical to the 1st thread of the fixture; (d) presence of visual signs of inflammation.
• For the control group: adult patient age ≥18 years old presented with: (a) one or more adjacent missing teeth in the posterior maxilla or mandible (positions premolar to molar); (b) adequate bone quality and availability for an implant placement of 4.5- 5.0 mm diameter and 8.5-13 mm length; (c) keratinized mucosa (KT) width of at least 3 mm.
• for both groups the patients give written consent to participate and attend the planned follow-up visits

Sponsors & Collaborators

• University of Baghdad: lead

Study Sites (1)

Talib A. Alnajaty

Karbala, 56001, Iraq

RECRUITING

Biospecimen

Retention: SAMPLES WITHOUT DNA

fixed peri-implant soft tissue sample

MeSH Terms

Conditions

Peri-Implantitis

Condition Hierarchy (Ancestors)

Periodontal Diseases; Mouth Diseases; Stomatognathic Diseases

Study Officials

• Talib A Alnajaty

  University of Baghdad

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Talib A Alnajaty

CONTACT

009647707905702; taleb.ali1105a@codental.uobaghdad.edu.iq

Talib A Alnajaty

CONTACT

009647707905702; talib.den777@yahoo.com

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: March 22, 2023
• First Posted: April 27, 2023
• Study Start: August 18, 2022
• Primary Completion: August 1, 2024
• Study Completion: August 15, 2024
• Last Updated: August 20, 2024

Record last verified: 2024-08

Locations

IR (1)