Peri-ImplantitisNCT04807725
Analysis of Genetic Variations in Patients With Peri-implantitis
An observational study of Peri-Implantitis, run by Egas Moniz - Cooperativa de Ensino Superior, CRL at 1 site in Portugal.
Trial summary
The primary objective of this study is to evaluate interleukin-1(IL-1) gene group polymorphisms in patients with peri-implantitis and to compare them with patients with peri-implant health (control group), taking into account smoking status, gender, age and history of periodontitis.The aim of this investigation is… Read more about this study
- Who is it for?
- Any ageHealthy volunteers can take part
- Conditions the study is for
- Peri-Implantitis
- What is being tested?
- Analysis of genetic polymorphisms and Biochemical analysis
- How many people
- 88 participants
- Where
- 1 sitePortugal
- Study dates
- 9 Mar 2021to 29 Jul 2022
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Study population: Patients included in the study will be recruited from the Dental Clinic Egas Moniz implant maintenance program and will only be used for this study. All possible candidates will receive a questionnaire and if the patient's medical history is in accordance with study inclusion criteria, and if they agree to participate, informed consent will be signed.
Who may be able to join
- patients with Caucasian parents and grandparents
- patients with dental implants placed at the Dental Clinic Egas Moniz or out
- patients with peri-implantitis diagnosis
- implants in function for at least 1 year
- patients included in a periodontal / peri-implant support program
- patients who agree to participate in the study and sign informed consent
Who cannot join
- patients with any systemic condition that affects the immune system
- pregnant women
- patients who have taken chronic antibiotics or anti-inflammatory drugs in the last 6 months
- patients who have undergone peri-implant treatment in the area to be evaluated
Trial locations and contacts
1 site in 1 country.
Portugal1 site, 1 recruiting
- Recruiting
Instituto Universitário Egas Moniz
Almada, Monte de Caparica, 2829-511
About this study
Official title: Association Between IL-1 and IL-1Ra Gene Polymorphisms With Peri-implantitis
The primary objective of this study is to evaluate interleukin-1(IL-1) gene group polymorphisms in patients with peri-implantitis and to compare them with patients with peri-implant health (control group), taking into account smoking status, gender, age and history of periodontitis.The aim of this investigation is also to look at the levels of the inflammatory response markers IL-1 beta, prostaglandin E2 (PGE2) and tumor necrosis factor alpha (TNF alpha) in the peri-implant crevicular fluid of patients with healthy oral implants in comparison with individuals with peri-implantitis, under consideration of the patients´ individual IL-1 genotype.
The main hypothesis is that individuals carrying the polymorphism in the IL-1 gene cluster are susceptible to develop peri-implantitis through altered IL-1 and IL-1 receptor antagonist (IL-1Ra) production. A second hypothesis is that both in healthy individuals and especially pronounced in patients having peri-implantitis, an IL-1-positive genotype will result in higher levels of inflammatory cytokines (IL-1 beta, PGE2 and TNF alpha) than an IL-1- negative genotype.
Read more
Patients included in the study will be recruited from the Dental Clinic Egas Moniz implant maintenance program and will only be used for this study. All possible candidates will receive a questionnaire and if the patient's medical history is in accordance with study inclusion criteria, and if they agree to participate, informed consent will be signed. All clinical data will be collected by the same examiner.
Genes IL-1A and IL-1B control the production of the proinflammatory proteins, IL-1 alpha and IL-1 beta, respectively. IL-1RN gene controls the synthesis of the IL-1Ra, which impedes the function of IL-1alpha and IL-1beta by competing for receptor binding. Polymorphisms of the following genes will be analyzed: IL-1A-889, IL-1B + 3954, IL-1B-511 and IL-1 RN from patients with peri-implantitis and peri-implant health. For the investigation of genetic polymorphisms, it will be collected a sample of cells from the jugal mucosa with the aid of a swab.
For the biochemical analysis of the inflammatory mediators IL-1 beta, TNF alpha and PGE2 a peri-implant crevicular fluid collection will be performed by inserting paper strips into peri-implant sulcus or pocket, in situations of peri-implantitis from the most affected location, while in situations of peri-implant health from the mesio-buccal location.
Read the detailed description
The study will be conducted according to the principles of the Helsinki Declaration (reviewed in 2013). Appropriate measures will be taken for the protection of patient data. The study was approved by Instituto Universitário Egas Moniz (IUEM) Scientific Council on 3 July 2019 and the approval of the Ethics Committee of Egas Moniz was received on 24 July 2019. Authorization was also obtained by the Clinical Direction of Egas Moniz Dental Clinic to carry out research work at the Clinic of the University.
The study will consist of two groups, the first consisting of patients with peri-implantitis (bleeding and / or suppuration on probing, probing depth (PD) equal or greater than 6mm and bone loss equal to or greater than 3mm) and the second group (control group) formed by patients with peri-implant health (peri implant mucosa without inflammatory signs and absence of peri-implant bone loss). The definition of peri-implantitis and peri-implant health will be in accordance with the new classification of periodontal and peri-implant diseases (American Academy of Periodontology (AAP) and European Federation of Periodontology (EFP) 2017)
A peri-implant probing examination (6 locations with a CP12 graduated periodontal probe) and evaluation of plaque accumulation and gingival indexes (4 locations) will be performed as usual at implant maintenance appointments. The presence of bleeding on probing or pus will also be evaluated. An implant control radiograph will be taken in cases where there is a probing depth more than 6mm. All clinical data will be collected by the same examiner. Prior to the study, a training and calibration exercise will be performed for PD measurements using patients not included in the study.
The periodontal condition of the patients will be also evaluated. To consider periodontal health, patients should have the following clinical characteristics: up to 10% of locations with bleeding on probing, absence of erythema and edema, absence of patient symptoms, absence of clinical attachment loss and bone loss and PD < 3mm (AAP and EFP 2017). A patient is a periodontitis case if: interdental clinical attachment loss is detectable at least 2 non-adjacent teeth, or buccal or oral clinical attachment loss >3mm with pocketing >3mm is detectable at least 2 teeth. The classification of periodontitis will be done on a multi-dimensional staging and grading system.
In the case of a peri-implant health situation, plaque control measures will be taken, while in cases of peri-implantitis the patient will be referred for a specific treatment appointment. In situations of patients with more than one implant affected by peri-implantitis, the one with the greatest bone loss will be chosen for the study.
The genetic analysis will be done at the IUEM Molecular Biology Laboratory with the DNA extraction technique followed by polymerase chain reaction followed by restriction fragment length polymorphism.
For the biochemical analysis the paper strips will be inserted into the peri-implant sulcus/ pocket until resistance is felt, waiting 30 seconds before removal. Visually contaminated samples (blood) will be discarded. Subsequently paper strips will be placed on Periotron® 8000 (Periotron Ide-interstate, NY, USA) for quantification of the collected peri-implant crevicular fluid volume. The strips of paper will then be placed in eppendorf tubes with filter and frozen at -80ºC until shipment to the Universidad Complutense de Madrid. At this university, the concentration of inflammatory mediators IL-1 beta and TNF alpha will be analyzed using multiplexed fluorescent sphere immunoassays using the Luminex® 100/200™ system and PGE2 by enzyme-linked immunosorbent assay (ELISA).
The prevalence of IL-1 gene group polymorphisms in patients with peri-implantitis and healthy ones will be compared by using appropriate inferential statistics methodologies (bivariate analysis/association tests), taking into account several sociodemographic and clinical variables: smoking status, gender, age and history of periodontitis. Based on a medium effect size (w=0.3), with 80% power and a 5% alpha level, the sample size for this study was calculated as n=88, thus, n= 44 for each group (periimplantitis and peri-implant health). Further, a multivariable regression logistic model will be constructed in order to evaluate the effect of those covariables and quantify the risk, through determination of the correspondent adjusted Odds Ratio (OR), towards the presence of peri-implantitis. Additionally, the levels of the inflammatory response markers IL-1 beta, PGE2 and TNF-alpha, present in the peri-implant crevicular fluid, will be compared between the group of patients with peri-implantitis and the patients with healthy oral implants, taking into account the above mentioned variables, by using appropriate inferential statistics methodologies (parametric/non parametric tests). All inferential analysis will be performed at a 5% significance level.
- Conditions
- Peri-Implantitis
- Being tested
- Analysis of genetic polymorphisms, Biochemical analysis
- Keywords
- peri-implantitis, gene polymorphisms, interleukin-1, dental implants
- Medical subject headings
- Peri-Implantitis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Analysis of genetic polymorphismsGenetic
For the investigation of genetic polymorphisms, it will be collected a sample of cells from the jugal mucosa with the aid of a swab. The genetic analysis will be done with the DNA extraction technique followed by PCR-RFLP techniques (polymerase chain reaction followed by restriction fragment length polymorphism).
Biochemical analysisOther
For the biochemical analysis of the inflammatory mediators IL-1beta, TNF-alpha and PGE2 a peri-implant crevicular fluid collection will be performed by inserting paper strips into peri-implant sulcus or pocket, in situations of peri-implantitis from the most affected location, while in situations of peri-implant health from the mesio-buccal location.
| Study group | Role | What they receive |
|---|---|---|
| Peri-implant health | Includes patients with peri implant mucosa without inflammatory signs and absence of peri-implant bone loss. Receives: Genetic: Analysis of genetic polymorphisms; Other: Biochemical analysis | |
| Peri-implantitis | Includes patients with bleeding and / or suppuration on probing, probing depth equal or greater than 6mm and bone loss equal to or greater than 3mm. Receives: Genetic: Analysis of genetic polymorphisms; Other: Biochemical analysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
Frequency of Participants with polymorphism in the IL-1 gene cluster
In the IL-1A-889 gene, two possible alleles are expected to be found, allele 1 (83 base pairs (bp) + 16 bp), allele 2 - allele with nucleotide sequence changed (99 bp). In the IL-1B + 3954 gene, two possible alleles are expected to be found, allele 1 (12 bp + 85 bp + 97 bp), allele 2 (12 bp + 182 bp). In the IL-1B-511 gene, two possible alleles are expected to be found, allele 1 (190bp + 114bp), allele 2 (304 bp). In relation to the polymorphism of the IL-1RN gene, 5 possible alleles are expected to be found according to the repeated base pair sequences: allele 1 (410 bp), allele 2 (240 bp), allele 3 (500 bp), allele 4 (325 bp), allele 5 (595 bp).
Measured: 1 month after sample collection
Secondary outcomes (1)
Concentration of inflammatory response markers IL-1 beta, PGE2 and TNF-alpha
The paper strips with peri-implant crevicular fluid (PICF) will be placed on Periotron® 8000 (Periotron Ide-interstate, NY, USA) for quantification of the collected PICF volume.The concentration of inflammatory mediators IL-1beta and TNF-alpha will be analyzed using multiplexed fluorescent sphere immunoassays using the Luminex® 100/200™ system and PGE2 by ELISA (enzyme-linked immunosorbent assay).
Measured: 1 month after sample collection
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Mar 2021
- Study start9 Mar 2021
- Primary completion29 Jul 2022 (estimated)
- Study completion29 Jul 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (17)Papers the sponsor has linked to this study.
- Other trials for Peri-ImplantitisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Enrolment
- 88 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Egas Moniz - Cooperativa de Ensino Superior, CRL
- Sponsor type
- University, hospital or other
- Collaborators
- Oral Reconstruction Foudation
- Responsible party
- Sponsor
- Investigators
- Ricardo Alves, Phd, Principal investigator, Egas Moniz
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04807725
- Sponsor's protocol ID
- PHDJMC
- Status last verified
- Mar 2022
- First submitted
- 18 Mar 2021
- Last updated
- 23 Mar 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: The collections of DNA samples were collected only for the purpose of analyzing the polymorphisms of the IL-1 gene group. Participants authorized their collection only for this purpose. For ethical and confidentiality reasons, these samples may not be accessible to other researchers. DNA samples will be eliminated after conducting the study.
Publications
Chen X, Zhao Y. Genetic Involvement in Dental Implant Failure: Association With Polymorphisms of Genes Modulating Inflammatory Responses and Bone Metabolism. J Oral Implantol. 2019 Aug;45(4):318-326. doi: 10.1563/aaid-joi-D-18-00212. Epub 2019 Jun 17.
PubMed 31207194Duarte PM, de Mendonca AC, Maximo MB, Santos VR, Bastos MF, Nociti Junior FH. Differential cytokine expressions affect the severity of peri-implant disease. Clin Oral Implants Res. 2009 May;20(5):514-20. doi: 10.1111/j.1600-0501.2008.01680.x. Epub 2009 Mar 11.
PubMed 19302394Feloutzis A, Lang NP, Tonetti MS, Burgin W, Bragger U, Buser D, Duff GW, Kornman KS. IL-1 gene polymorphism and smoking as risk factors for peri-implant bone loss in a well-maintained population. Clin Oral Implants Res. 2003 Feb;14(1):10-7. doi: 10.1034/j.1600-0501.2003.140102.x.
PubMed 12562360Gruica B, Wang HY, Lang NP, Buser D. Impact of IL-1 genotype and smoking status on the prognosis of osseointegrated implants. Clin Oral Implants Res. 2004 Aug;15(4):393-400. doi: 10.1111/j.1600-0501.2004.01026.x.
PubMed 15248873Lachmann S, Kimmerle-Muller E, Axmann D, Scheideler L, Weber H, Haas R. Associations between peri-implant crevicular fluid volume, concentrations of crevicular inflammatory mediators, and composite IL-1A -889 and IL-1B +3954 genotype. A cross-sectional study on implant recall patients with and without clinical signs of peri-implantitis. Clin Oral Implants Res. 2007 Apr;18(2):212-23. doi: 10.1111/j.1600-0501.2006.01322.x.
PubMed 17348886Petkovic-Curcin A, Zeljic K, Cikota-Aleksic B, Dakovic D, Tatic Z, Magic Z. Association of Cytokine Gene Polymorphism with Peri-implantitis Risk. Int J Oral Maxillofac Implants. 2017 Sep/Oct;32(5):e241-e248. doi: 10.11607/jomi.5814.
PubMed 28906511He K, Jian F, He T, Tang H, Huang B, Wei N. Analysis of the association of TNF-alpha, IL-1A, and IL-1B polymorphisms with peri-implantitis in a Chinese non-smoking population. Clin Oral Investig. 2020 Feb;24(2):693-699. doi: 10.1007/s00784-019-02968-z. Epub 2019 May 24.
PubMed 31127430McDowell TL, Symons JA, Ploski R, Forre O, Duff GW. A genetic association between juvenile rheumatoid arthritis and a novel interleukin-1 alpha polymorphism. Arthritis Rheum. 1995 Feb;38(2):221-8. doi: 10.1002/art.1780380210.
PubMed 7848312Tarlow JK, Blakemore AI, Lennard A, Solari R, Hughes HN, Steinkasserer A, Duff GW. Polymorphism in human IL-1 receptor antagonist gene intron 2 is caused by variable numbers of an 86-bp tandem repeat. Hum Genet. 1993 May;91(4):403-4. doi: 10.1007/BF00217368.
PubMed 8500797Hamdy AA, Ebrahem MA. The effect of interleukin-1 allele 2 genotype (IL-1a(-889) and IL-1b(+3954)) on the individual's susceptibility to peri-implantitis: case-control study. J Oral Implantol. 2011 Jun;37(3):325-34. doi: 10.1563/AAID-JOI-D-09-00117.1. Epub 2010 Jun 16.
PubMed 20594066Dereka X, Mardas N, Chin S, Petrie A, Donos N. A systematic review on the association between genetic predisposition and dental implant biological complications. Clin Oral Implants Res. 2012 Jul;23(7):775-88. doi: 10.1111/j.1600-0501.2011.02329.x. Epub 2011 Dec 12.
PubMed 22151432Laine ML, Leonhardt A, Roos-Jansaker AM, Pena AS, van Winkelhoff AJ, Winkel EG, Renvert S. IL-1RN gene polymorphism is associated with peri-implantitis. Clin Oral Implants Res. 2006 Aug;17(4):380-5. doi: 10.1111/j.1600-0501.2006.01249.x.
PubMed 16907768Huynh-Ba G, Lang NP, Tonetti MS, Zwahlen M, Salvi GE. Association of the composite IL-1 genotype with peri-implantitis: a systematic review. Clin Oral Implants Res. 2008 Nov;19(11):1154-62. doi: 10.1111/j.1600-0501.2008.01596.x.
PubMed 18983319Andreiotelli M, Koutayas SO, Madianos PN, Strub JR. Relationship between interleukin-1 genotype and peri-implantitis: a literature review. Quintessence Int. 2008 Apr;39(4):289-98.
PubMed 19081897Liao J, Li C, Wang Y, Ten M, Sun X, Tian A, Zhang Q, Liang X. Meta-analysis of the association between common interleukin-1 polymorphisms and dental implant failure. Mol Biol Rep. 2014 May;41(5):2789-98. doi: 10.1007/s11033-014-3133-6. Epub 2014 Jan 23.
PubMed 24452718
Study at a glance
From the registry record, last updated by the sponsor on 23 Mar 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Association Between IL-1 and IL-1Ra Gene Polymorphisms With Peri-implantitis
- ClinicalTrials.gov ID
- NCT04807725
- Acronym / sponsor ID
- PHDJMC
- Conditions
- Peri-Implantitis
- Keywords
- peri-implantitis, gene polymorphisms, interleukin-1, dental implants
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 88 participants (estimated)
- Lead sponsor
- Egas Moniz - Cooperativa de Ensino Superior, CRLUniversity, hospital or other
- Collaborators
- Oral Reconstruction Foudation
- Study start
- 9 Mar 2021 (actual)
- Primary completion
- 29 Jul 2022 (estimated)
- Study completion
- 29 Jul 2022 (estimated)
- First posted
- 19 Mar 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary objective of this study is to evaluate interleukin-1(IL-1) gene group polymorphisms in patients with peri-implantitis and to compare them with patients with peri-implant health (control group), taking into account smoking status, gender, age and history of periodontitis.The aim of this investigation is also to look at the levels of the inflammatory response markers IL-1 beta, prostaglandin E2 (PGE2) and tumor necrosis factor alpha (TNF alpha) in the peri-implant crevicular fluid of patients with healthy oral implants in comparison with individuals with peri-implantitis, under consideration of the patients´ individual IL-1 genotype.
The main hypothesis is that individuals carrying the polymorphism in the IL-1 gene cluster are susceptible to develop peri-implantitis through altered IL-1 and IL-1 receptor antagonist (IL-1Ra) production. A second hypothesis is that both in healthy individuals and especially pronounced in patients having peri-implantitis, an IL-1-positive genotype will result in higher levels of inflammatory cytokines (IL-1 beta, PGE2 and TNF alpha) than an IL-1- negative genotype.
Patients included in the study will be recruited from the Dental Clinic Egas Moniz implant maintenance program and will only be used for this study. All possible candidates will receive a questionnaire and if the patient's medical history is in accordance with study inclusion criteria, and if they agree to participate, informed consent will be signed. All clinical data will be collected by the same examiner.
Genes IL-1A and IL-1B control the production of the proinflammatory proteins, IL-1 alpha and IL-1 beta, respectively. IL-1RN gene controls the synthesis of the IL-1Ra, which impedes the function of IL-1alpha and IL-1beta by competing for receptor binding. Polymorphisms of the following genes will be analyzed: IL-1A-889, IL-1B + 3954, IL-1B-511 and IL-1 RN from patients with peri-implantitis and peri-implant health. For the investigation of genetic polymorphisms, it will be collected a sample of cells from the jugal mucosa with the aid of a swab.
For the biochemical analysis of the inflammatory mediators IL-1 beta, TNF alpha and PGE2 a peri-implant crevicular fluid collection will be performed by inserting paper strips into peri-implant sulcus or pocket, in situations of peri-implantitis from the most affected location, while in situations of peri-implant health from the mesio-buccal location.
Detailed description
The study will be conducted according to the principles of the Helsinki Declaration (reviewed in 2013). Appropriate measures will be taken for the protection of patient data. The study was approved by Instituto Universitário Egas Moniz (IUEM) Scientific Council on 3 July 2019 and the approval of the Ethics Committee of Egas Moniz was received on 24 July 2019. Authorization was also obtained by the Clinical Direction of Egas Moniz Dental Clinic to carry out research work at the Clinic of the University.
The study will consist of two groups, the first consisting of patients with peri-implantitis (bleeding and / or suppuration on probing, probing depth (PD) equal or greater than 6mm and bone loss equal to or greater than 3mm) and the second group (control group) formed by patients with peri-implant health (peri implant mucosa without inflammatory signs and absence of peri-implant bone loss). The definition of peri-implantitis and peri-implant health will be in accordance with the new classification of periodontal and peri-implant diseases (American Academy of Periodontology (AAP) and European Federation of Periodontology (EFP) 2017)
A peri-implant probing examination (6 locations with a CP12 graduated periodontal probe) and evaluation of plaque accumulation and gingival indexes (4 locations) will be performed as usual at implant maintenance appointments. The presence of bleeding on probing or pus will also be evaluated. An implant control radiograph will be taken in cases where there is a probing depth more than 6mm. All clinical data will be collected by the same examiner. Prior to the study, a training and calibration exercise will be performed for PD measurements using patients not included in the study.
The periodontal condition of the patients will be also evaluated. To consider periodontal health, patients should have the following clinical characteristics: up to 10% of locations with bleeding on probing, absence of erythema and edema, absence of patient symptoms, absence of clinical attachment loss and bone loss and PD < 3mm (AAP and EFP 2017). A patient is a periodontitis case if: interdental clinical attachment loss is detectable at least 2 non-adjacent teeth, or buccal or oral clinical attachment loss >3mm with pocketing >3mm is detectable at least 2 teeth. The classification of periodontitis will be done on a multi-dimensional staging and grading system.
In the case of a peri-implant health situation, plaque control measures will be taken, while in cases of peri-implantitis the patient will be referred for a specific treatment appointment. In situations of patients with more than one implant affected by peri-implantitis, the one with the greatest bone loss will be chosen for the study.
The genetic analysis will be done at the IUEM Molecular Biology Laboratory with the DNA extraction technique followed by polymerase chain reaction followed by restriction fragment length polymorphism.
For the biochemical analysis the paper strips will be inserted into the peri-implant sulcus/ pocket until resistance is felt, waiting 30 seconds before removal. Visually contaminated samples (blood) will be discarded. Subsequently paper strips will be placed on Periotron® 8000 (Periotron Ide-interstate, NY, USA) for quantification of the collected peri-implant crevicular fluid volume. The strips of paper will then be placed in eppendorf tubes with filter and frozen at -80ºC until shipment to the Universidad Complutense de Madrid. At this university, the concentration of inflammatory mediators IL-1 beta and TNF alpha will be analyzed using multiplexed fluorescent sphere immunoassays using the Luminex® 100/200™ system and PGE2 by enzyme-linked immunosorbent assay (ELISA).
The prevalence of IL-1 gene group polymorphisms in patients with peri-implantitis and healthy ones will be compared by using appropriate inferential statistics methodologies (bivariate analysis/association tests), taking into account several sociodemographic and clinical variables: smoking status, gender, age and history of periodontitis. Based on a medium effect size (w=0.3), with 80% power and a 5% alpha level, the sample size for this study was calculated as n=88, thus, n= 44 for each group (periimplantitis and peri-implant health). Further, a multivariable regression logistic model will be constructed in order to evaluate the effect of those covariables and quantify the risk, through determination of the correspondent adjusted Odds Ratio (OR), towards the presence of peri-implantitis. Additionally, the levels of the inflammatory response markers IL-1 beta, PGE2 and TNF-alpha, present in the peri-implant crevicular fluid, will be compared between the group of patients with peri-implantitis and the patients with healthy oral implants, taking into account the above mentioned variables, by using appropriate inferential statistics methodologies (parametric/non parametric tests). All inferential analysis will be performed at a 5% significance level.
Study design
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Peri-implant health | – | Genetic: Analysis of genetic polymorphisms, Other: Biochemical analysisIncludes patients with peri implant mucosa without inflammatory signs and absence of peri-implant bone loss. |
| Peri-implantitis | – | Genetic: Analysis of genetic polymorphisms, Other: Biochemical analysisIncludes patients with bleeding and / or suppuration on probing, probing depth equal or greater than 6mm and bone loss equal to or greater than 3mm. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Patients included in the study will be recruited from the Dental Clinic Egas Moniz implant maintenance program and will only be used for this study. All possible candidates will receive a questionnaire and if the patient's medical history is in accordance with study inclusion criteria, and if they agree to participate, informed consent will be signed.
Key inclusion criteria (6 listed)
- patients with Caucasian parents and grandparents
- patients with dental implants placed at the Dental Clinic Egas Moniz or out
- patients with peri-implantitis diagnosis
- implants in function for at least 1 year
- patients included in a periodontal / peri-implant support program
Key exclusion criteria (4 listed)
- patients with any systemic condition that affects the immune system
- pregnant women
- patients who have taken chronic antibiotics or anti-inflammatory drugs in the last 6 months
- patients who have undergone peri-implant treatment in the area to be evaluated
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Analysis of genetic polymorphismsFor the investigation of genetic polymorphisms, it will be collected a sample of cells from the jugal mucosa with the aid of a swab. The genetic analysis will be done with the DNA extraction technique followed by PCR-RFLP techniques (polymerase chain reaction followed by restriction fragment length polymorphism). | Genetic | Peri-implant health, Peri-implantitis |
| Biochemical analysisFor the biochemical analysis of the inflammatory mediators IL-1beta, TNF-alpha and PGE2 a peri-implant crevicular fluid collection will be performed by inserting paper strips into peri-implant sulcus or pocket, in situations of peri-implantitis from the most affected location, while in situations of peri-implant health from the mesio-buccal location. | Other | Peri-implant health, Peri-implantitis |
Primary outcome
Frequency of Participants with polymorphism in the IL-1 gene cluster
Time frame: 1 month after sample collection
In the IL-1A-889 gene, two possible alleles are expected to be found, allele 1 (83 base pairs (bp) + 16 bp), allele 2 - allele with nucleotide sequence changed (99 bp). In the IL-1B + 3954 gene, two possible alleles are expected to be found, allele 1 (12 bp + 85 bp + 97 bp), allele 2 (12 bp + 182 bp). In the IL-1B-511 gene, two possible alleles are expected to be found, allele 1 (190bp + 114bp), allele 2 (304 bp). In relation to the polymorphism of the IL-1RN gene, 5 possible alleles are expected to be found according to the repeated base pair sequences: allele 1 (410 bp), allele 2 (240 bp), allele 3 (500 bp), allele 4 (325 bp), allele 5 (595 bp).
1 secondary outcome
Concentration of inflammatory response markers IL-1 beta, PGE2 and TNF-alpha
Time frame: 1 month after sample collection
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Mar 2022.
- Background: PubMed 31207194Chen X, Zhao Y. Genetic Involvement in Dental Implant Failure: Association With Polymorphisms of Genes Modulating Inflammatory Responses and Bone Metabolism. J Oral Implantol. 2019 Aug;45(4):318-326. doi: 10.1563/aaid-joi-D-18-00212. Epub 2019 Jun 17.
- Background: PubMed 19302394Duarte PM, de Mendonca AC, Maximo MB, Santos VR, Bastos MF, Nociti Junior FH. Differential cytokine expressions affect the severity of peri-implant disease. Clin Oral Implants Res. 2009 May;20(5):514-20. doi: 10.1111/j.1600-0501.2008.01680.x. Epub 2009 Mar 11.
- Background: PubMed 12562360Feloutzis A, Lang NP, Tonetti MS, Burgin W, Bragger U, Buser D, Duff GW, Kornman KS. IL-1 gene polymorphism and smoking as risk factors for peri-implant bone loss in a well-maintained population. Clin Oral Implants Res. 2003 Feb;14(1):10-7. doi: 10.1034/j.1600-0501.2003.140102.x.
- Background: PubMed 15248873Gruica B, Wang HY, Lang NP, Buser D. Impact of IL-1 genotype and smoking status on the prognosis of osseointegrated implants. Clin Oral Implants Res. 2004 Aug;15(4):393-400. doi: 10.1111/j.1600-0501.2004.01026.x.
- Background: PubMed 17348886Lachmann S, Kimmerle-Muller E, Axmann D, Scheideler L, Weber H, Haas R. Associations between peri-implant crevicular fluid volume, concentrations of crevicular inflammatory mediators, and composite IL-1A -889 and IL-1B +3954 genotype. A cross-sectional study on implant recall patients with and without clinical signs of peri-implantitis. Clin Oral Implants Res. 2007 Apr;18(2):212-23. doi: 10.1111/j.1600-0501.2006.01322.x.
- Background: PubMed 28906511Petkovic-Curcin A, Zeljic K, Cikota-Aleksic B, Dakovic D, Tatic Z, Magic Z. Association of Cytokine Gene Polymorphism with Peri-implantitis Risk. Int J Oral Maxillofac Implants. 2017 Sep/Oct;32(5):e241-e248. doi: 10.11607/jomi.5814.
- Background: PubMed 31127430He K, Jian F, He T, Tang H, Huang B, Wei N. Analysis of the association of TNF-alpha, IL-1A, and IL-1B polymorphisms with peri-implantitis in a Chinese non-smoking population. Clin Oral Investig. 2020 Feb;24(2):693-699. doi: 10.1007/s00784-019-02968-z. Epub 2019 May 24.
- Background: PubMed 7848312McDowell TL, Symons JA, Ploski R, Forre O, Duff GW. A genetic association between juvenile rheumatoid arthritis and a novel interleukin-1 alpha polymorphism. Arthritis Rheum. 1995 Feb;38(2):221-8. doi: 10.1002/art.1780380210.
- Background: PubMed 8500797Tarlow JK, Blakemore AI, Lennard A, Solari R, Hughes HN, Steinkasserer A, Duff GW. Polymorphism in human IL-1 receptor antagonist gene intron 2 is caused by variable numbers of an 86-bp tandem repeat. Hum Genet. 1993 May;91(4):403-4. doi: 10.1007/BF00217368.
- Background: PubMed 20594066Hamdy AA, Ebrahem MA. The effect of interleukin-1 allele 2 genotype (IL-1a(-889) and IL-1b(+3954)) on the individual's susceptibility to peri-implantitis: case-control study. J Oral Implantol. 2011 Jun;37(3):325-34. doi: 10.1563/AAID-JOI-D-09-00117.1. Epub 2010 Jun 16.
- Background: PubMed 22151432Dereka X, Mardas N, Chin S, Petrie A, Donos N. A systematic review on the association between genetic predisposition and dental implant biological complications. Clin Oral Implants Res. 2012 Jul;23(7):775-88. doi: 10.1111/j.1600-0501.2011.02329.x. Epub 2011 Dec 12.
- Background: PubMed 16907768Laine ML, Leonhardt A, Roos-Jansaker AM, Pena AS, van Winkelhoff AJ, Winkel EG, Renvert S. IL-1RN gene polymorphism is associated with peri-implantitis. Clin Oral Implants Res. 2006 Aug;17(4):380-5. doi: 10.1111/j.1600-0501.2006.01249.x.
- Individual participant dataSharing planned: No. The collections of DNA samples were collected only for the purpose of analyzing the polymorphisms of the IL-1 gene group. Participants authorized their collection only for this purpose. For ethical and confidentiality reasons, these samples may not be accessible to other researchers. DNA samples will be eliminated after conducting the study.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ricardo Alves, Phd principal investigator
Egas Moniz
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Peri-Implantitis, run by Egas Moniz - Cooperativa de Ensino Superior, CRL at 1 site in Portugal.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 23 Mar 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Portugal. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Ricardo Alves, Phd (00351212946767, ralves@egasmoniz.edu.pt), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Frequency of Participants with polymorphism in the IL-1 gene cluster (time frame: 1 month after sample collection). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04807725, which also lists 17 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Mar 2022.