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

NCT05902208 | Recruiting Phase 3 DMC

• 1 other identifier: 20-API-02
• Study Type: interventional
• Target: 142
• Locations: 1 country
• Sites: 3

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.

Conditions

Periodontitis Chronic Generalized Severe

Outcome Measures

Primary Outcomes (1)

• 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)

  Efficacy will be assessed by measuring the periodontal pocket depth using a graduated (in millimeter) and coloured probe used at low pressure (\<0.2N) 28 days after the end of antiviral treatment (visit 2) and 2 months after scaling and root planing (visit 3), during the periodontal reassessment visit

  28 days after the end of antiviral treatment and 2 months after root surfacing

Secondary Outcomes (11)

• 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).

  6 and 8 months after scaling and root planing

• 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).

  6 and 8 months after scaling and root planing

• 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).

  6 and 8 months after root planing

• 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

  6 and 8 months after root planing

• Compare changes in the Epstein-Barr Virus (EBV) levels, between the two groups of patients

  From the start of treatment (V0) to the end of the follow-up (V5, 8 months)

Study Arms (2)

Valaciclovir

EXPERIMENTAL

Drug: Antiviral treatment with conventional non-surgical treatment

Placebo

PLACEBO COMPARATOR

Drug: Placebo with conventional non-surgical treatment

Interventions

Antiviral treatment with conventional non-surgical treatment DRUG

Valaciclovir, a antiviral treatment will be added to the conventional non-surgical treatment of generalized periodontitis. One gram per day will be administered during 28 days.

Valaciclovir

Placebo with conventional non-surgical treatment DRUG

Placebo of valaciclovir (same composition, without active substance) will be added to the conventional non-surgical treatment of generalized periodontitis. One gram a day will be administered during 28 days.

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• Necrotizing periodontitis
• Pathologies requiring prophylactic antibiotics therapy (which may influence treatment)
• 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)
• 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.

Sponsors & Collaborators

• Centre Hospitalier Universitaire de Nice: lead

Study Sites (3)

CHU de Nice

Nice, Alpes Maritimes, 06000, France

RECRUITING

APHM

Marseille, Bouches Du Rhone, 13385, France

NOT YET RECRUITING

CHU de Rennes

Rennes, Ille-et-Vilaine, 35000, France

RECRUITING

Central Study Contacts

Séverine VINCENT-BUGNAS

CONTACT

04 92 03 32 70; vincent-bugnas.s@chu-nice.fr

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 5, 2023
• First Posted: June 13, 2023
• Study Start: February 5, 2024
• Primary Completion: May 1, 2026
• Study Completion: May 1, 2026
• Last Updated: February 9, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share

Locations

FR (3)