Biological Responses Affecting Early-stage Dental Implant Placement in Patients With History of Periodontitis

Identification of Biological Responses as a Causal Link for the Increased Peri-implantitis in Patients With History of Periodontitis

This prospective parallel, double-blind, four-arm randomised controlled clinical study is planned to assess the difference in the level of the inflammatory biomarkers expressed following the placement of the first dental implant in patients with history of periodontitis (successfully treated) and healthy controls without the disease, during implant osseointegration period. The subjects in both groups will also be randomised to receive one of the two types of implants provided which have different surface treatment.

Study Overview

• Status: Active, not recruiting
• Conditions: Periodontitis; Peri-Implantitis; Peri-implant Mucositis
• Intervention / Treatment: Other: Megagen implant placement; Other: Biomate-Swiss implant

Detailed Description

This is a prospective, parallel, double-blind, four-arm randomised clinical control study, aims to investigate the changes of clinical parameters and pro-inflammatory biomarkers expression and the shift following the first dental implant placement in patients who have been successfully treated for periodontitis, compared with healthy control without the disease.

The main questions to answer are:

1. Why do patients with history of periodontitis are at a greater risk to develop peri-implantitis than patients without history of periodontitis?
2. Is there any difference in the microbial composition, histological and immunological reaction of the host's dental plaque, peri-implant soft tissue, gingival crevicular fluids (GCF) of adjacent teeth and peri-implant sulcular fluids (PISF) following implant placement in patients with and without a history of periodontitis? The test group will consist of subjects with stabilised periodontitis, whilst the control group will consist of healthy patients with no history of periodontitis, as identified via history taking and clinical screening. Periodontal condition will be determined based on the new 2017 periodontal classification. All participants in both groups will be randomised to receive one of two types of implants with different surface treatment.

Clinical measurement, GCF and PISF will be collected around the single implant and adjacent teeth, at the following stages (time-point):

• Baseline (pre-operative)
• After implant placement (prior to the second stage surgery)
• After implant exposure (prior to the crown restoration)
• 3-month after the implant is restored
• Soft tissue will be obtained during the first stage (baseline) and second stage implant surgery (post-operative) and analysed.

• Study Type: Interventional
• Enrollment (Actual): 29
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Malaysia
  • Wilayah Persekutuan
    • Kuala Lumpur, Wilayah Persekutuan, Malaysia, 50603
      • Faculty Of Dentistry, University of Malaya

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Specific inclusion criteria for test group:

   • History of periodontitis but currently stable
   • Must have successfully completed active periodontal treatment at least 4 months prior to the commencement of study

2. Specific inclusion criteria for control group:

   • No history of periodontitis, with minimal age-related radiographic bone loss
   • Reason for losing the tooth/teeth was not due to periodontal problem

3. General inclusion criteria:

   • Medically healthy
   • Aged between 30 to 65 years old
   • Non-smoker, or quit smoking at least 12 months before study commencement
   • Good oral hygiene (full mouth plaque score (FMPS)<20%, full mouth bleeding score (FMBS)<15%)
   • Indicated for a single implant placement in the posterior region, with adjacent and contralateral natural tooth
   • Intact inter-cuspal position

Exclusion Criteria:

• Previous history of dental implant placement
• Currently pregnant or intend to be pregnant, and/or lactating mothers
• Taking long-term medicines which may affect gingival tissue and oral microbiome, e.g. antibiotics, anticoagulants, anticonvulsants, immunosuppressants and calcium channel blockers.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group T-A; 7 patients with history of periodontitis	Other: Megagen implant placement; Megagen implant with sand-blasted, large-grit, acid-etched (SLA) and nano-calcium ions incorporated surface
Experimental: Group T-B; 7 patients with history of periodontitis	Other: Biomate-Swiss implant; Biomate-Swiss implant with precision dimension laser (PDL) surface
Active Comparator: Group C-A; 7 patients without history of periodontitis	Other: Megagen implant placement; Megagen implant with sand-blasted, large-grit, acid-etched (SLA) and nano-calcium ions incorporated surface
Active Comparator: Group C-B; 8 patients without history of periodontitis	Other: Biomate-Swiss implant; Biomate-Swiss implant with precision dimension laser (PDL) surface

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Level of matrix metalloproteinase (MMP)-8 expressed in the gingival crevicular and peri-implant sulcular fluids during the early-stage of dental implant placement	To measure the absolute quantification of MMP-8 level expressed during the implant osseointegration period in all study groups via ELISA method.	From baseline (1st time-point (TP1)) to 1st stage surgery (implant placement - TP2), after 2nd stage surgery (implant exposure (TP3) and 3-months after implant crown restoration (final visit- TP4)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Shift of the microbial composition in the supragingival dental plaque, identified via 16S rRNA next generation sequencing	Identification and comparison of supragingival dental plaque bacteria species/genus and the shift of the bacterial composition during the early-stage of dental implant placement between study groups	From baseline (1st time-point (TP1)) to 1st stage surgery (implant placement - TP2), after 2nd stage surgery (implant exposure (TP3) approximately 3 months after the 1st stage surgery) and 3-months after implant crown restoration (final visit- TP4)
Shift of proteome profiles in the gingival crevicular and peri-implant sulcular fluids during the early-stage of dental implant placement	To assess the protein profile and levels of expression of the pro-inflammatory cytokines in GCF and gingival tissue via liquid chromatography-electrospray ionization tandem mass spectrometry (LC-MS) proteomic analysis following osseointegration.	From baseline (1st time-point (TP1)) to 1st stage surgery (implant placement - TP2), after 2nd stage surgery (implant exposure (TP3) approximately 3 months after the 1st stage surgery) and 3-months after implant crown restoration (final visit- TP4)
Histological changes in the peri-implant soft tissue before and after implant placement	Number and co-localisation of cells with MMP-8, pro-inflammatory (M1)- and anti-inflammatory (M2)-related cytokines via hematoxylin and eosin staining, immunohistochemistry and immunofluorescence analysis	Between first stage (baseline/pre) and second stage implant surgery (post-operative) at 3 months after the first surgery
Changes in the clinical parameters during the early-stage implant placement	To assess intra-oral clinical parameters changes (i.e. patient-level and tooth-level mean periodontal pocket depth (mm) and clinical attachment level (mm); full mouth plaque score (%) and bleeding score (%)) following the first dental implant placement, each time-point (TP). The deeper the depth/higher the level or percentage means the worse the condition is.	From baseline (1st time-point (TP1)) to 1st stage surgery (implant placement - TP2), after 2nd stage surgery (implant exposure (TP3) approximately 3 months after the 1st stage surgery) and 3-months after implant crown restoration (final visit- TP4)

Collaborators and Investigators

• Sponsor: University of Malaya
• Investigators: Principal Investigator: Norul H Mohamad-Hassan, DDS,MCD, University of Malaya

Study record dates

Study Major Dates

• Study Start (Actual): March 4, 2021
• Primary Completion (Actual): May 30, 2023
• Study Completion (Estimated): May 30, 2025

Study Registration Dates

• First Submitted: January 17, 2023
• First Submitted That Met QC Criteria: April 17, 2023
• First Posted (Actual): April 28, 2023

Study Record Updates

• Last Update Posted (Actual): October 18, 2023
• Last Update Submitted That Met QC Criteria: October 17, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: dental implant; dental plaque; next generation sequencing; proteomic analysis; peri-implant soft tissue; histological analysis; history of periodontitis; matrix metalloproteinase (MMP)-8; gingival crevicular fluids; peri-implant sulcular fluids
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Stomatognathic Diseases; Periodontal Diseases; Mouth Diseases; Periodontitis; Mucositis; Peri-Implantitis
• Other Study ID Numbers: DF RD2002/0002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual participant data that underlie the results reported in this article after deidentification. Researchers should provide a methodologically sound proposal and directed to the principal investigator by email.
• IPD Sharing Time Frame: Beginning 3 months and ending 5 years following article(s) publication.
• IPD Sharing Access Criteria: To gain access, data requestors will need to provide a methodologically sound proposal and sign a data access agreement.

Drug and device information, study documents

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