Clinical trial NCT05902208: Contribution of an Antiviral Drug (Valaciclovir) in the Treatment of Generalized Periodontitis (Stage III or IV and Grade A, B or C): Prospective, Randomized and Double Blind Clinical Trial
Official title: Contribution of an Antiviral Drug (Valaciclovir) in the Treatment of Generalized Periodontitis (Stage III or IV and Grade A, B or C): Prospective, Randomized and Double Blind Clinical Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Periodontitis Chronic Generalized Severe
Lead sponsor: Centre Hospitalier Universitaire de Nice
Sponsor class: OTHER
First posted: 2023-06-13
Enrollment: 142
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Periodontitis is an inflammatory pathology that destroys periodontitis and causes tooth loosening. Its high incidence, combined with very high oral and systemic morbidity, places this pathology at the heart of global public health priorities. The current therapeutic management of periodontitis is not satisfactory because it often leads to a stabilization of the disease, marked by frequent recurrences, especially severe forms. Improving the treatment of patients with periodontitis is therefore an essential priority.

If gingival bacterial dysbiosis is a major contributing factor, this model has clinical-biological limitations that suggest that other etiological factors are involved, and worsen the pathology. In particular, the literature provides clear evidence that periodontal lesions are mostly infected with Herpes EBV, CMV and HSV-1 viruses and that periodontal infection with these viruses is very directly correlated with disease progression (severity). In addition, our work provides new cellular and molecular data that demonstrate mechanisms of active EBV infection of cells and periodontal structures, and highlight inflammatory and necrotic effects associated with this infection. Given these observations and the high pathogenicity of herpes viruses, all known to be powerful inflammatory, lytic and immunomodulatory agents, it seems difficult not to evoke a direct etiopathogenic role of these viruses capable of acting synergistically with periodontopathogenic bacteria.

In this context, the use of an antiviral appears as a very attractive therapeutic proposal to effectively treat periodontitis in combination with conventional treatments. This original and innovative proposal can also be easily and quickly validated in a randomized therapeutic trial through the availability of antiviral molecules that are non-toxic and very specific to human herpes viruses that are derivatives of aciclovir.


Eligibility criteria: Inclusion criteria:

* Age ≥ 18
* Diagnosis of periodontitis induced by bacterial biofilms of dental plaque, generalized, stage III or IV and grade A, B or C
* Patients of childbearing age will need to use an effective method of contraception for the duration of their study participation
* Signature of informed consent
* Membership of a social security scheme

Exclusion criteria:

* Necrotizing periodontitis
* Pathologies requiring prophylactic antibiotics therapy (which may influence treatment)
* Non-surgical periodontal treatment completed within 6 months prior to inclusion
* Patients with enhanced protection, namely lactating women, persons deprived of liberty by judicial or administrative decision, person over 18 under legal protection
* Patients who do not accept conventional therapy (gingival debridement not covered by the social security system (performed in each center)
* Periodontitis as a direct manifestation of systemic diseases
* Major systemic pathologies (diabetes, HIV, cancers, immunocompromised patients)
* Negative serology for EBV: a blood test will be performed. the results will be communicated to the patient by the dental surgeon
* Pregnant woman: a blood pregnancy test will be carried out for women of childbearing age who do not have contraception. Results will be communicated to the patient by the dental surgeon
* Renal failure (creatinine clearance \< 60 mL/min)
* Systemic antibiotic therapy or any medication affecting the periodontal environment (systemic antibiotics, antiepileptics, immunosuppressants, calcium inhibitors) taken within 6 months of inclusion
* Nephrotoxic medications (aminoglycosides, organoplatinums, iodized contrast agents, methotrexate, pentamidine, foscarnet, cyclosporine and tacrolimus)
* Hypersensitivity to valaciclovir, aciclovir or one of the excipients
* History of DRESS syndrome under valaciclovir treatment.

Primary outcomes:
measure: Compare the efficacy of antiviral treatment (valaciclovir) with conventional non-surgical treatment (scaling and root planing) to conventional treatment with a placebo for generalized periodontitis (stage III or IV and grade A, B or C)
timeFrame: 28 days after the end of antiviral treatment and 2 months after root surfacing
Secondary outcomes:
measure: Compare the efficacy of valaciclovir associated with conventional treatment to conventional treatment with placebo in the management of generalized periodontitis using a conventional periodontal clinical index, the Bleeding on Probing (BOP).
timeFrame: 6 and 8 months after scaling and root planing
measure: Compare the efficacy of valaciclovir associated with conventional treatment to conventional treatment with placebo in the management of generalized periodontitis using a conventional periodontal clinical index, the O'Leary's plaque index (PI).
timeFrame: 6 and 8 months after scaling and root planing
measure: Compare the efficacy of valaciclovir associated with conventional treatment to conventional treatment with placebo in the management of generalized periodontitis using a conventional periodontal clinical index, the Clinical Attachment Level (CAL).
timeFrame: 6 and 8 months after root planing
measure: Compare the efficacy of valaciclovir associated with conventional treatment to conventional treatment with placebo in the management of generalized periodontitis using a conventional periodontal clinical index, the periodontal pocket depth after probing
timeFrame: 6 and 8 months after root planing
measure: Compare changes in the Epstein-Barr Virus (EBV) levels, between the two groups of patients
timeFrame: From the start of treatment (V0) to the end of the follow-up (V5, 8 months)
measure: Compare changes in the CytoMegaloVirus (CMV) levels between the two groups of patients
timeFrame: From the start of treatment (V0) to the end of the follow-up (V5, 8 months)
measure: Compare changes in the Herpes Simplex Virus-1 (HSV-1) levels between the 2 patient groups.
timeFrame: From the start of treatment (V0) to the end of the follow-up (V5, 8 months)
measure: Compare changes in main bacterial species quantity of the periodontal biofilm (bacterial mapping) between both groups.
timeFrame: Before (V0), at the end (V2) and after the antiviral treatment (V5)
measure: Compare frequency of periodontal surgery from visit (V3) (at periodontal reassessment) between both groups
timeFrame: 2 months after the start of the antiviral treatment (V3)
measure: Compare changes of oral health impact on the quality of life of patients between both groups
timeFrame: Before (V0), 2 months (V3) and 8 months (V5) after the start of the antiviral treatment
measure: Evaluate the medico-economic impact of valaciclovir used with conventional treatment compared to conventional treatment alone.
timeFrame: From the start of treatment (V0) to the end of the follow-up (V5, 8 months)
Other outcomes:
Locations:
city: Nice
country: France
facility: CHU de Nice
state: Alpes Maritimes
city: Marseille
country: France
facility: APHM
state: Bouches Du Rhone
city: Rennes
country: France
facility: CHU de Rennes
state: Ille-et-Vilaine
Study officials:
References: