Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT03631849 |
| Other study ID # |
18-AOI-10 |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
November 2, 2020 |
| Est. completion date |
May 2026 |
Study information
| Verified date |
February 2024 |
| Source |
Centre Hospitalier Universitaire de Nice |
| Contact |
Séverine VINCENT-BUGNAS |
| Phone |
0492033270 |
| Email |
vincent-bugnas.s[@]chu-nice.fr |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Peri-implantitis is a high prevalence disease that affects Dental Implants, and can lead to
the implant loss if untreated. This condition isn't really well known, and treatments can't
provide predictable results. The aim of this study will be to establish a link between the
Epstein Barr Virus and the Peri-implantitis, as suggested by recent studies.
Description:
Just like the tissues surrounding a natural tooth, the structures around a dental implant,
the support of an artificial tooth, can host a severe inflammation, called peri-implantitis.
Once it has developed, peri-implantitis is irreversible, and causes the loss of the mucosa
and osseous support of the implant, leading inevitably to its loss. The mean prevalence of
peri-implantitis is about 10% of all implants, and this pathology affects up to 20% of
patients, from 5 to 10 years after surgery. This disease is, therefore, a real public health
issue, and a major medico-economic challenge for present-day dentistry. If, like
periodontitis (infection/inflammation of the tissues surrounding a natural tooth),
peri-implantitis seems to be multifactorial, it is proven that a diverse and pathogenic
bacterial flora colonizes the peri-implant tissues and plays a major role in bone loss. Poor
oral hygiene and uncontrolled diabetes are among the known risk factors. Furthermore, a link
has been clearly established between an antecedent of periodontitis and the risk of
contracting peri-implantitis. However, this infection tends to progress slowly, before any
clinical symptoms appear (e.g. suppuration, pain, implant mobility) which means that the
pathology is advanced and is, most often, going to lead to implant loss. At present only very
early diagnosis and treatment (at the mucositis stage) are able to stabilize the evolution of
this disease. Moreover, present-day treatments (surgical debridement, with or without bone
regeneration) are not easily reproducible, leading to an unfavorable prognosis. If prevention
of peri-implant disease (follow-up examination, radiography, peri-implant probing and perfect
oral hygiene) is essential to maintaining healthy peri-implant tissues, it does not guarantee
the implant's sustainability. Indeed, peri-implant tissues are scar tissues, less well
vascularized than periodontal tissues, and without the periodontal ligament, which links the
tooth to the surrounding bone and plays an immune-protective role. Thus, peri-implant sites
are less well-organized to resist oral bacterial assault, which certainly explains the high
prevalence of peri-implant diseases. No correlation was found between the implant surface
treatment or the implant design, and the development of a peri-implantitis.
However, neither the onset, nor the trigger, nor even the mechanisms underlying the
progression of peri-implantitis are clearly understood at the moment. Even if the
inflammatory role of bacterial dysbiosis remains predominant, several lines of evidence
suggest that the bacterial etiology is not sufficient to totally explain the pathology,
especially the initial stages, its non-reversible inflammatory nature, and the failure of
antibiotic therapies.
A possible synergy between the peri-implant bacteria pathogenicity and the
replication/activation of endogenous herpes virus seems to be a hypothesis in the development
of peri-implantitis. This model of viro-bacterial synergy represents one of the major
mechanistic advances concerning periodontitis.
A previous study, (Vincent et al., 20135), in particular, proved that the Epstein-Barr Virus
(EBV) infection, an ubiquitous human herpesvirus with chronic oral replication, was
detectable in healthy gums, and grew significantly in the deepest periodontal pockets.
Moreover, this study clearly established for the first time that the epithelial cells
surrounding periodontally affected teeth were frequently infected by EBV, and showed a high
susceptibility to apoptosis. This epithelial damage characterized by the death of infected
cells, certainly contributes to the loss of attachment between bone and teeth, promoting
bacterial invasion and serious inflammation.
There is still little data on the involvement of EBV in peri-implantitis, but it has been
recently proved that the virus is present twelve times more often in an affected peri-implant
area than in a healthy area, with a positive predictive value between EBV and
peri-implantitis of 90%. Moreover, EBV has been associated to the most severe cases of
peri-implantitis. In addition, a significant correlation between EBV and mucositis
(reversible initial stage of peri-implant inflammation) seems to exist. If it is accepted
that untreated mucositis systematically evolves into irreversible periimplantitis any early
identification of mucositis markers would allow treatment at an early stage of the disease.
Finally, this data is also supported by our own recent preliminary results that show the
presence of EBV in peri-implantitis sites.
All these results point to the proposition that EBV may play a role in the onset and/or the
development of peri-implantitis. The objective of this research project is to test this
hypothesis and see if the results for periodontitis could be applied to peri-implantitis.
This is an original project that it now seems essential to investigate as part of a clinical
study. It draws on the already established expertise of the research laboratory of the
Faculty of Dentistry (MICORALIS, directed by Dr Alain Doglio), associated with Nice
University Hospital Dental Department, and is the continuity of Dr Vincent's work. The
evidence of an implication of EBV in peri-implantitis could open a way to identifying a new
early pathogenic marker and lead to a new antiviral therapeutic approach, which could, in
time, prevent implant loss.
