Periodontitis Chronic Generalized SeverePhase 3HERPARONCT05902208
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
A Phase 3 study testing Antiviral treatment with conventional non-surgical treatment in people with Periodontitis Chronic Generalized Severe, run by Centre Hospitalier Universitaire de Nice at 3 sites in France.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Periodontitis Chronic Generalized Severe
- What is being tested?
- Antiviral treatment with conventional non-surgical treatment
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 142 participants
- Where
- 3 sitesFrance
- Study dates
- 5 Feb 2024to May 2026
- Phase
- Phase 3
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 14Show fewer
- 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.
Trial locations and contacts
3 sites in 1 country.
France3 sites, 3 recruiting
- Not yet recruiting
APHM
Marseille, Bouches Du Rhone, 13385
Virginie MONNET-CORTI, 04 91 38 84 45 ext. +33, virginie.monnet@ap-hm.fr
Virginie MONNET-CORTI
- Recruiting
CHU de Nice
Nice, Alpes Maritimes, 06000
Severine VINCENT-BUGNAS, 04 92 03 32 70 ext. +33, vincent-bugnas.s@chu-nice.fr
Severine VINCENT-BUGNAS
- Recruiting
CHU de Rennes
Rennes, Ille-et-Vilaine, 35000
Sylvie JEANNE, sylvie.jeanne@chu-rennes.fr
Sylvie JEANNE
About this study
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
- Being tested
- Antiviral treatment with conventional non-surgical treatment, Placebo with conventional non-surgical treatment
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Antiviral treatment with conventional non-surgical treatmentDrug
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.
Placebo with conventional non-surgical treatmentDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Valaciclovir | Experimental | Not described Receives: Drug: Antiviral treatment with conventional non-surgical treatment |
| Placebo | Placebo comparator | Not described Receives: Drug: Placebo with conventional non-surgical treatment |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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).
The Bleeding on Probing (BOP) assesses the gingival inflammation based on gum bleeding after periodontal probing. It corresponds to the number of sites with bleeding divided by the total number of measured sites, expressed as a percentage. This index will be collected from the same tooth that was determined for the primary objective.
Measured: 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).
O'Leary's Plaque Index (PI) measures the amount of plaque on the tooth (hygiene index). It is calculated by dividing the number of sites with plaque by the total number of measured sites, expressed as a percentage. This index will be collected from the same tooth that was determined for the primary objective.
Measured: 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).
The Clinical Attachment Level (CAL) assesses the degree of impairment, by measuring the distance between the bottom of the pocket and the amelo-cemental junction of the tooth, expressed in millimeters. This index will be collected from the same tooth that was determined for the primary objective.
Measured: 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
The periodontal pocket depth will be measured using a graduated (in millimeter) and coloured probe used at low pressure (<0.2N). This index will be collected from the same tooth that was determined for the primary objective.
Measured: 6 and 8 months after root planing
Compare changes in the Epstein-Barr Virus (EBV) levels, between the two groups of patients
The Epstein-Barr Virus (EBV) levels in periodontal sample is measured through quantitative Polymerase Chain Reaction (PCR) of their viral genomes, throughout patient follow-up.
Measured: From the start of treatment (V0) to the end of the follow-up (V5, 8 months)
Compare changes in the CytoMegaloVirus (CMV) levels between the two groups of patients
The CytoMegaloVirus (CMV) levels in periodontal sample is measured through quantitative Polymerase Chain Reaction (PCR) of their viral genomes, throughout patient follow-up.
Measured: From the start of treatment (V0) to the end of the follow-up (V5, 8 months)
Compare changes in the Herpes Simplex Virus-1 (HSV-1) levels between the 2 patient groups.
The Herpes Simplex Virus-1 (HSV-1) levels in periodontal sample is measured through quantitative Polymerase Chain Reaction (PCR) of their viral genomes, throughout patient follow-up.
Measured: From the start of treatment (V0) to the end of the follow-up (V5, 8 months)
Compare changes in main bacterial species quantity of the periodontal biofilm (bacterial mapping) between both groups.
The twenty bacterial species levels in periodontal sample is measured through quantitative Polymerase Chain Reaction (PCR) of the bacterial genomes, before, at the end and after the antiviral treatment (V0, V2 and V5)
Measured: Before (V0), at the end (V2) and after the antiviral treatment (V5)
Compare frequency of periodontal surgery from visit (V3) (at periodontal reassessment) between both groups
Surgery is available from visit 3 (during periodontal reassessment) and is indicated for patients with a good degree of hygiene (PI ≤ 20%) but with persistent pockets (PPS > 5mm) and bleeding at probing
Measured: 2 months after the start of the antiviral treatment (V3)
Compare changes of oral health impact on the quality of life of patients between both groups
The oral health impact on quality of life is based on the Oral Health Impact Profile 14 (OHIP-14) questionnaire, which measures the impact of oral conditions on the well-being and quality of life of the patients. It will be measured before, 2 months and 8 months after the start of the antiviral treatment.
Measured: Before (V0), 2 months (V3) and 8 months (V5) after the start of the antiviral treatment
Evaluate the medico-economic impact of valaciclovir used with conventional treatment compared to conventional treatment alone.
The medico-economic impact is evaluated by the incremental cost-effectiveness ratio by divided the difference in the cost of each strategy to the difference in efficiency (number of patients who had therapeutical surgery during the follow-up period)
Measured: From the start of treatment (V0) to the end of the follow-up (V5, 8 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jun 2023
- Study start5 Feb 2024
- Primary completionMay 2026 (estimated)
- Study completionMay 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Periodontitis Chronic Generalized SevereStudies of the same condition, open and under way.
- More trials run by Centre Hospitalier Universitaire de NiceThe sponsor's other registered studies.
- 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
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 142 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Centre Hospitalier Universitaire de Nice
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05902208
- Sponsor's protocol ID
- 20-API-02
- Acronym
- HERPARO
- Status last verified
- Feb 2024
- First submitted
- 5 Jun 2023
- Last updated
- 9 Feb 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT05902208
- Acronym / sponsor ID
- HERPARO / 20-API-02
- Conditions
- Periodontitis Chronic Generalized Severe
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 142 participants (estimated)
- Lead sponsor
- Centre Hospitalier Universitaire de NiceUniversity, hospital or other
- Study start
- 5 Feb 2024 (actual)
- Primary completion
- May 2026 (estimated)
- Study completion
- May 2026 (estimated)
- First posted
- 13 Jun 2023 (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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Valaciclovir | Experimental | Drug: Antiviral treatment with conventional non-surgical treatment |
| Placebo | Placebo comparator | Drug: Placebo with conventional non-surgical treatment |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (14 listed)
- 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)
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 |
|---|---|---|
| Antiviral treatment with conventional non-surgical treatmentValaciclovir, 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. | Drug | Valaciclovir |
| Placebo with conventional non-surgical treatmentPlacebo 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. | Drug | Placebo |
Primary outcome
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)
Time frame: 28 days after the end of antiviral treatment and 2 months after root surfacing
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
11 secondary outcomes
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).
Time frame: 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).
Time frame: 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).
Time frame: 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
Time frame: 6 and 8 months after root planing
Compare changes in the Epstein-Barr Virus (EBV) levels, between the two groups of patients
Time frame: From the start of treatment (V0) to the end of the follow-up (V5, 8 months)
Compare changes in the CytoMegaloVirus (CMV) levels between the two groups of patients
Time frame: From the start of treatment (V0) to the end of the follow-up (V5, 8 months)
Compare changes in the Herpes Simplex Virus-1 (HSV-1) levels between the 2 patient groups.
Time frame: From the start of treatment (V0) to the end of the follow-up (V5, 8 months)
Compare changes in main bacterial species quantity of the periodontal biofilm (bacterial mapping) between both groups.
Time frame: Before (V0), at the end (V2) and after the antiviral treatment (V5)
Compare frequency of periodontal surgery from visit (V3) (at periodontal reassessment) between both groups
Time frame: 2 months after the start of the antiviral treatment (V3)
Compare changes of oral health impact on the quality of life of patients between both groups
Time frame: Before (V0), 2 months (V3) and 8 months (V5) after the start of the antiviral treatment
Evaluate the medico-economic impact of valaciclovir used with conventional treatment compared to conventional treatment alone.
Time frame: From the start of treatment (V0) to the end of the follow-up (V5, 8 months)
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Feb 2024.
- Individual participant dataSharing planned: No
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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.
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Antiviral treatment with conventional non-surgical treatment in people with Periodontitis Chronic Generalized Severe, run by Centre Hospitalier Universitaire de Nice at 3 sites in France.
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 5 inclusion and 14 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 9 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in France. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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 Séverine VINCENT-BUGNAS (04 92 03 32 70 ext. +33, vincent-bugnas.s@chu-nice.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome 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) (time frame: 28 days after the end of antiviral treatment and 2 months after root surfacing). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 9 Feb 2024.