Immunological-Clinical Evaluation of the Etiopathogenesis of Peri-Implantitis

NCT07012915 | Recruiting

• 1 other identifier: KA220-HED
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

A total of 100 adult volunteers of both sexes will be enrolled in the project. The study will be conducted within an international consortium formed for the project, comprising the following institutions: Wroclaw Medical University (Poland), Sapienza University of Rome (Italy), University of Barcelona (Spain), University of Bern (Switzerland), and Egas Moniz University (Portugal). Each international partner institution will recruit 20 volunteers as participants in the experiment. Each of the participating institutions will submit an application to their respective local bioethics committee for approval to conduct the medical experiment. Each partner institution will conduct procedures at their respective clinical locations. Eligibility Criteria participants must have undergone previous implant treatment that has resulted in active, advanced peri-implantitis. Exclusion Criteria: General and local contraindications for surgical procedures Pregnancy; Use of bisphosphonates or other antiresorptive medications in medical history Laboratory Analysis Procedures. During the initial visit, patients will undergo a medical interview and a dental examination with regard to: Oral Hygiene Indices; Periodontal disease indices. For the implant site, the following parameters will be evaluated: Pocket Depth Bleeding on Probing Width and height of the attached gingiva Possible implant mobility, assessed using the Mobility Index Following the clinical examination, each participant will be referred for a Cone Beam Computed Tomography (CBCT) scan with measurements including: Bone loss percentage for each of the four implant surfaces, Bone density. Next, a 20ml venous blood sample will be collected from the antecubital vein of each participant and sent to a laboratory for further analysis, including: Hematological Inflammation Indices: Systemic Immune-Inflammation Index, Aggregate Index of Systemic Inflammation, Complete blood count, Lipid profile, APOA., APOBg, Inflammatory markers, albumin, total protein, total ferritin, fibrinogen, Cytokine profile, HOMA2 Parameters, Thyroid profile, Vitamin D level Next, each participant will undergo implant explantation surgery, during which tissue samples will be collected for further analysis. Implant surface will be analyzed using: light microscopy, scanning electron microscopy, corrosion testing. Follow-Up will be scheduled four weeks later with following evaluation: Clinical assessment of the implantation site. A CBCT scan to assess bone structure in the post-implantation region, with measurements including percentage of bone loss. Moreover, 20ml of venous blood will be collected from the antecubital vein of each participant. The blood sample will be preserved and sent to an analytical laboratory for further testing, including for same as previously mentioned tests.

Conditions

Peri-Implantitis

Keywords

Perii-implantitis; Titanium alloys corosion; Titanium implants

Outcome Measures

Primary Outcomes (26)

• Blood testing, total blood count, and indices derived from it.

  Hematological Inflammation Indices: Systemic Immune-Inflammation Index (SII) calculated as follows: SII=NEUxPLT/LYMPH

  On the day of implant removal (before implant removal) and 4 weeks after.

• Blood testing, total blood count, and indices derived from it.

  Hematological Inflammation Indices: Aggregate Index of Systemic Inflammation (AISI) calculated as follows: AISI= NEU×PLTxMON/LYMP

  On the day of implant removal (before implant removal) and 4 weeks after.

• Blood testing, lipid profile.

  CHOL mg/dl , HDL mg/dl, LDL mg/dl, TG mg/dl, APOA1 mg/dl, APOB mg/dl

  On the day of implant removal (before implant removal) and 4 weeks after.

• Blood testing, Inflammatory markers.

  Inflammatory markers: CRP mg/l, albumin (ALB) mg/dl, TP mg/dl,TF mg/dl, FIB mg/dl

  On the day of implant removal (before implant removal) and 4 weeks after.

• Blood testing, Inflammatory marker.

  ESR mm/h

  On the day of implant removal (before implant removal) and 4 weeks after.

• Blood testing, Cytokine profile.

  TNF- α pg/ml , IL- 1β pg/ml, IL-6 pg/ml, IL-8 pg/ml, IL-10 pg/ml

  On the day of implant removal (before implant removal) and 4 weeks after.

• Blood testing, HOMA2 Parameters

  HOMA2 Parameters - Glucose mg/dl, C-Peptide mg/dl,

  On the day of implant removal (before implant removal) and 4 weeks after.

• Blood testing, HOMA2 Parameters

  Insulin mU/ml

  On the day of implant removal (before implant removal) and 4 weeks after.

• Blood testing, HOMA2 Parameters

  HBA1C %

  On the day of implant removal (before implant removal) and 4 weeks after.

• Blood testing, Thyroid profile

  TSH μIU/ml

  On the day of implant removal (before implant removal) and 4 weeks after.

• Blood testing, Thyroid profile

  FT3 ng/l, FT4 ng/l

  On the day of implant removal (before implant removal) and 4 weeks after.

• Blood testing, Thyroid profile

  T3 ng/dl, T4 ng/dl

  On the day of implant removal (before implant removal) and 4 weeks after.

• Blood testing, Thyroid profile

  rT3 ng/ml

  On the day of implant removal (before implant removal) and 4 weeks after.

• Blood testing, Vitamin D3 level

  25(OH)D, 1.25(OH)2 D3 ng/ml

  On the day of implant removal (before implant removal) and 4 weeks after.

• Clinical examination - general, oral cavity

  Oral Hygiene Index (OHI) %, Aproximal Plaque Index (API) %

  On the day of implant removal (before implant removal) and 4 weeks after.

• Clinical examination - general, oral cavity, utilizing a UNC15 periodontal probe

  Community Index of Periodontal Treatment Needs (CPITN)

  On the day of implant removal (before implant removal).

• Clinical examination - implant site, utilizing a UNC15 periodontal probe

  Pocket Depth (PD) - measured on four surfaces around the implant in mm.

  On the day of implant removal (before implant removal).

• Clinical examination - implant site, utilizing a UNC15 periodontal probe

  Bleeding on Probing (BoP) Index - Yes or No. (0 or 1).

  On the day of implant removal (before implant removal).

• Clinical examination - implant site, utilizing a UNC15 periodontal probe

  Width and height of the attached gingiva (HKT, WKT) in mm.

  On the day of implant removal (before implant removal).

• Clinical examination - implant site, utilizing a UNC15 periodontal probe

  Possible implant mobility, assessed using the Mobility Index (MOB) acc to Misch, Grade: 0,1,2 or 3

  On the day of implant removal (before implant removal).

• Radiology-based evaluation

  Cone-Beam Computed Tomography: Bone loss percentage on the implant site (%), calculated as the ratio of bone defect depth from the implant platform to the base of the defect, relative to the total implant length, assessed separately for each of the four implant surfaces (mesial, distal, buccal, and lingual/palatal)

  On the day of implant removal (before implant removal).

• Radiology-based evaluation

  Cone-Beam Computed Tomography: Bone density on the implant site (before and after implant removal), measured in Hounsfield units (HU)

  On the day of implant removal (before implant removal) and 4 weeks after.

• Implant surface evaluation, light microscopy

  Assessment of the implant surface, identifying areas with fatigue-related material degradation, such as microcracks.

  Within 48 hours after implant removal

• Implant surface evaluation, Scanning electron microscopy

  Assessment of the implant surface, identifying areas with fatigue-related material degradation, such as microcracks.

  Within 48 hours after implant removal

• Implant surface evaluation - detection of other metals presented in the titanium alloy.

  Energy-dispersive X-ray spectroscopy (EDS)

  Within 48 hours after implant removal

• Titanium ions concentration in tissues attached to implant' surface

  Inductively coupled plasma mass spectrometry (ICP-MS)

  Within 48 hours after implant removal

Study Arms (1)

Study group

EXPERIMENTAL

Every participant will achieve same intervention when it comes to surgical treatment, clinical examination, radiology evaluation and defined parameters of blood serum.

Diagnostic Test: Blood testing

Interventions

Blood testing DIAGNOSTIC_TEST

Blood sample will be collected twice for each participants procedding and following dental implant removal. Cone Beam Computed Tomography will be applied to evaluate the shape, severity of bone defect in direct viscinity of the implant.

Also known as: Radiation, Surgery

Study group

Eligibility Criteria

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

You may qualify if:

• PD (Pocket Depth) at the implant site exceeds 6mm,
• Positive BoP (Bleeding on Probing) index
• Bone loss exceeding 66% on at least one implant surface

You may not qualify if:

• General and local contraindications for surgical procedures
• Pregnancy
• Use of bisphosphonates or other antiresorptive medications in medical history

Sponsors & Collaborators

• Wroclaw Medical University: lead
• University of Bern: collaborator
• University of Barcelona: collaborator
• University of Roma La Sapienza: collaborator
• Egas Moniz - Cooperativa de Ensino Superior, CRL: collaborator

Study Sites (1)

Oral Surgery Department Wroclaw Medical University

Wroclaw, Lower Silesian Voivodeship, 50425, Poland

RECRUITING

Related Publications (13)

• Elani HW, Starr JR, Da Silva JD, Gallucci GO. Trends in Dental Implant Use in the U.S., 1999-2016, and Projections to 2026. J Dent Res. 2018 Dec;97(13):1424-1430. doi: 10.1177/0022034518792567. Epub 2018 Aug 3.

  PMID: 30075090 BACKGROUND

• Fu JH, Wang HL. Breaking the wave of peri-implantitis. Periodontol 2000. 2020 Oct;84(1):145-160. doi: 10.1111/prd.12335.

  PMID: 32844418 BACKGROUND

• Schwarz F, Claus C, Becker K. Correlation between horizontal mucosal thickness and probing depths at healthy and diseased implant sites. Clin Oral Implants Res. 2017 Sep;28(9):1158-1163. doi: 10.1111/clr.12932. Epub 2016 Jul 26.

  PMID: 27458093 BACKGROUND

• Schwarz F, Derks J, Monje A, Wang HL. Peri-implantitis. J Periodontol. 2018 Jun;89 Suppl 1:S267-S290. doi: 10.1002/JPER.16-0350.

  PMID: 29926957 BACKGROUND

• Albrektsson T, Canullo L, Cochran D, De Bruyn H. "Peri-Implantitis": A Complication of a Foreign Body or a Man-Made "Disease". Facts and Fiction. Clin Implant Dent Relat Res. 2016 Aug;18(4):840-9. doi: 10.1111/cid.12427. Epub 2016 May 30.

  PMID: 27238274 BACKGROUND

• Pettersson M, Kelk P, Belibasakis GN, Bylund D, Molin Thoren M, Johansson A. Titanium ions form particles that activate and execute interleukin-1beta release from lipopolysaccharide-primed macrophages. J Periodontal Res. 2017 Feb;52(1):21-32. doi: 10.1111/jre.12364. Epub 2016 Mar 14.

  PMID: 26987886 BACKGROUND

• Tsave O, Petanidis S, Kioseoglou E, Yavropoulou MP, Yovos JG, Anestakis D, Tsepa A, Salifoglou A. Role of Vanadium in Cellular and Molecular Immunology: Association with Immune-Related Inflammation and Pharmacotoxicology Mechanisms. Oxid Med Cell Longev. 2016;2016:4013639. doi: 10.1155/2016/4013639. Epub 2016 Apr 11.

  PMID: 27190573 BACKGROUND

• Scibior A, Pietrzyk L, Plewa Z, Skiba A. Vanadium: Risks and possible benefits in the light of a comprehensive overview of its pharmacotoxicological mechanisms and multi-applications with a summary of further research trends. J Trace Elem Med Biol. 2020 Sep;61:126508. doi: 10.1016/j.jtemb.2020.126508. Epub 2020 Apr 12.

  PMID: 32305626 BACKGROUND

• Grande F, Tucci P. Titanium Dioxide Nanoparticles: a Risk for Human Health? Mini Rev Med Chem. 2016;16(9):762-9. doi: 10.2174/1389557516666160321114341.

  PMID: 26996620 BACKGROUND

• Zhang HM, Cao J, Tang BP, Wang YQ. Effect of TiO(2) nanoparticles on the structure and activity of catalase. Chem Biol Interact. 2014 Aug 5;219:168-74. doi: 10.1016/j.cbi.2014.06.005. Epub 2014 Jun 12.

  PMID: 24931876 BACKGROUND

• Chen WQ, Zhang SM, Qiu J. Surface analysis and corrosion behavior of pure titanium under fluoride exposure. J Prosthet Dent. 2020 Aug;124(2):239.e1-239.e8. doi: 10.1016/j.prosdent.2020.02.022. Epub 2020 May 10.

  PMID: 32402439 BACKGROUND

• Trepanier C, Tabrizian M, Yahia LH, Bilodeau L, Piron DL. Effect of modification of oxide layer on NiTi stent corrosion resistance. J Biomed Mater Res. 1998 Winter;43(4):433-40. doi: 10.1002/(sici)1097-4636(199824)43:43.0.co;2-#.

  PMID: 9855202 BACKGROUND

• Chouirfa H, Bouloussa H, Migonney V, Falentin-Daudre C. Review of titanium surface modification techniques and coatings for antibacterial applications. Acta Biomater. 2019 Jan 1;83:37-54. doi: 10.1016/j.actbio.2018.10.036. Epub 2018 Oct 26.

  PMID: 30541702 BACKGROUND

MeSH Terms

Conditions

Peri-Implantitis

Interventions

Hematologic Tests; Radiation

Condition Hierarchy (Ancestors)

Periodontal Diseases; Mouth Diseases; Stomatognathic Diseases

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Physical Phenomena

Study Officials

• Marzena Dominiak, Prof

  Wroclaw Medical Univeristy

  STUDY CHAIR

Central Study Contacts

Pawel Kubasiewicz-Ross, PhD, DDS

CONTACT

504075920; pawel.kubasiewicz-ross@umw.edu.pl

Jacek Matys, PhD, DDS

CONTACT

791511789; jacek.matys@umw.edu.pl

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Healthy adult participants, suffering from Peri-Implantitis. Every participant from a total number of 100 will have blood sample collected twice before and 4 weeks following implant removal for detailed evaluation. Furthermore, the Cone Beam Computed Tomography will be applied to evaluate the severity and shape of bone defect. Removed implants will be send for detailed chemical evaluation.

Study Record Dates

• First Submitted: May 14, 2025
• First Posted: June 10, 2025
• Study Start: July 1, 2025
• Primary Completion: April 1, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: July 10, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Within 12 months after finishing the study.
• Access Criteria: All anonymized (due to General Data Protection Policy) data will be available on demand.

Locations

PL (1)