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

Primary Purpose

Periodontitis, Peri-implant Mucositis, Peri-Implantitis

Status
Active
Phase
Not Applicable
Locations
Malaysia
Study Type
Interventional
Intervention
Megagen implant placement
Biomate-Swiss implant
Sponsored by
University of Malaya
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Periodontitis focused on measuring dental implant, history of periodontitis, matrix metalloproteinase (MMP)-8, histological analysis, next generation sequencing, dental plaque, gingival crevicular fluids, peri-implant sulcular fluids, peri-implant soft tissue, proteomic analysis

Eligibility Criteria

30 Years - 65 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria: 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 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 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.

Sites / Locations

  • Faculty of Dentistry, University of Malaya

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Active Comparator

Active Comparator

Arm Label

Group T-A

Group T-B

Group C-A

Group C-B

Arm Description

7 patients with history of periodontitis

7 patients with history of periodontitis

7 patients without history of periodontitis

8 patients without history of periodontitis

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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
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.
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
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.

Full Information

First Posted
January 17, 2023
Last Updated
October 17, 2023
Sponsor
University of Malaya
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1. Study Identification

Unique Protocol Identification Number
NCT05834946
Brief Title
Biological Responses Affecting Early-stage Dental Implant Placement in Patients With History of Periodontitis
Official Title
Identification of Biological Responses as a Causal Link for the Increased Peri-implantitis in Patients With History of Periodontitis
Study Type
Interventional

2. Study Status

Record Verification Date
April 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
March 4, 2021 (Actual)
Primary Completion Date
May 30, 2023 (Actual)
Study Completion Date
May 30, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Malaya

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
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.
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: Why do patients with history of periodontitis are at a greater risk to develop peri-implantitis than patients without history of periodontitis? 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Periodontitis, Peri-implant Mucositis, Peri-Implantitis
Keywords
dental implant, history of periodontitis, matrix metalloproteinase (MMP)-8, histological analysis, next generation sequencing, dental plaque, gingival crevicular fluids, peri-implant sulcular fluids, peri-implant soft tissue, proteomic analysis

7. Study Design

Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
Test group: Patient with history of periodontitis Control group: Patient without history of periodontitis Patients in both groups will be randomised to receive one of two type of implants with different surface characteristics.
Masking
ParticipantCare ProviderOutcomes Assessor
Masking Description
All participants will be blinded from the randomisation. An opaque envelope will be used to conceal the implant designation and will only be revealed to the operator after the site is ready for implant placement. A blinded researcher will be assigned as clinical assessor who will not be involved with the surgical procedure, subject recruitment nor consent taking. An assistant who is not involved with the research will also be asked to re-code the sample tubes to ensure blinding for data/sample analysis.
Allocation
Randomized
Enrollment
29 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Group T-A
Arm Type
Experimental
Arm Description
7 patients with history of periodontitis
Arm Title
Group T-B
Arm Type
Experimental
Arm Description
7 patients with history of periodontitis
Arm Title
Group C-A
Arm Type
Active Comparator
Arm Description
7 patients without history of periodontitis
Arm Title
Group C-B
Arm Type
Active Comparator
Arm Description
8 patients without history of periodontitis
Intervention Type
Other
Intervention Name(s)
Megagen implant placement
Intervention Description
Megagen implant with sand-blasted, large-grit, acid-etched (SLA) and nano-calcium ions incorporated surface
Intervention Type
Other
Intervention Name(s)
Biomate-Swiss implant
Intervention Description
Biomate-Swiss implant with precision dimension laser (PDL) surface
Primary Outcome Measure Information:
Title
Level of matrix metalloproteinase (MMP)-8 expressed in the gingival crevicular and peri-implant sulcular fluids during the early-stage of dental implant placement
Description
To measure the absolute quantification of MMP-8 level expressed during the implant osseointegration period in all study groups via ELISA method.
Time Frame
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 Measure Information:
Title
Shift of the microbial composition in the supragingival dental plaque, identified via 16S rRNA next generation sequencing
Description
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
Time Frame
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)
Title
Shift of proteome profiles in the gingival crevicular and peri-implant sulcular fluids during the early-stage of dental implant placement
Description
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.
Time Frame
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)
Title
Histological changes in the peri-implant soft tissue before and after implant placement
Description
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
Time Frame
Between first stage (baseline/pre) and second stage implant surgery (post-operative) at 3 months after the first surgery
Title
Changes in the clinical parameters during the early-stage implant placement
Description
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.
Time Frame
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)

10. Eligibility

Sex
All
Gender Based
Yes
Gender Eligibility Description
Female and male
Minimum Age & Unit of Time
30 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: 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 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 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Norul H Mohamad-Hassan, DDS,MCD
Organizational Affiliation
University of Malaya
Official's Role
Principal Investigator
Facility Information:
Facility Name
Faculty of Dentistry, University of Malaya
City
Kuala Lumpur
State/Province
Wilayah Persekutuan
ZIP/Postal Code
50603
Country
Malaysia

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing 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.

Learn more about this trial

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

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