Impact of a Newly Formulated Toothpaste in Tooth Staining Associated With Chlorhexidine Rinses

Dental staining may interfere with compliance with chlorhexidine mouth rinse use

Thus, developing strategies to control tooth staining associated with chlorhexidine use may be relevant for improving compliance. Thus, a new anti-staining toothpaste formulation (Dentaid, Barcelona, Spain) has been recently developed, aiming to interfere with the development of extrinsic staining associated with chlorhexidine use (preventive action), but also with the capacity of removing staining already formed. For that, the proposed formulation includes hexametaphosphate, tripolyphosphate and polyvinylpyrrolidone (PVP), within its ingredients. Thus, it may be relevant to test the efficacy of this new anti-staining toothpaste formulation in two consecutive randomized clinical trials (RCTs).

Objectives The primary objective of these RCTs will be to evaluate the capacity of preventing tooth staining, associated with the use of a chlorhexidine mouth rinse, adjunctive to subgingival instrumentation (step 2 of periodontal therapy) (RCT #1). As secondary objective, the capacity of eliminating or reducing tooth staining already present will be assessed (RCT #2).

The primary objective of these RCTs will be to evaluate the capacity of preventing tooth staining, associated with the use of a chlorhexidine mouth rinse, adjunctive to subgingival instrumentation (step 2 of periodontal therapy) (RCT #1). As secondary objective, the capacity of eliminating or reducing tooth staining already present will be assessed (RCT #2).

Additional objectives will include to test: (1) the safety of the tested formulation, in terms of adverse events and tolerability; (2) patient´s evaluation of the product, by means of patient-reported outcome measures (PROMs); and (3) clinical impact of the tested formulation in terms of periodontal clinical outcomes.

Consecutive subjects, referred to the Post-Graduate Periodontal Clinic in the University Complutense, Madrid, seeking for treatment of periodontitis in stages I-III will be screened, and enrolled in the clinical trials if they fulfil the following criteria and accept to participate by filling an informed consent

Two consecutive parallel, double-blind, randomized, placebo-controlled, 2-week, clinical trials have been designed.

Screening visit After completing a questionnaire including the subject's medical health status, medication and smoking habit \[smoker defined when currently smoking ≥ 9 cigarettes per day\], a careful oral health evaluation will be carried out. If subjects met the inclusion/exclusion criteria, the investigator will inform them about the aims and details of the study and will request their voluntary participation. Once they accept, by signing the Institutional Review Board (IRB) approved informed consent form, they will be enrolled in the study.

Pre-treatment visit At this visit the oral health of each participant, identified by a unique trial number, will be examined. Clinical parameters will be recorded around all teeth, except the third molars.

Treatment visits All interventions, included in the steps 1 and 2 of periodontal therapy will be implemented according to the patient´s needs. Specifically, subgingival instrumentation will be performed in two sessions, with a maximum interval of one week, with hand and automatic devices, under local anaesthesia. Full-mouth dental polishing (air-polishing) will be performed immediately after the second session, to eliminate any dental staining.

Immediately after the second session of subgingival instrumentation (initial visit, RCT #1) subjects will be randomly assigned to one of two groups, test or placebo. Randomization will be performed using true random numbers from a computer-generated list, stratified for tobacco smoking (smokers of 10 or more cigarettes per day versus other smokers, former smokers and non-smokers):

1. The experimental group will use three times daily a provided manual toothbrush with the test toothpaste (Dentaid, Barcelona, Spain), followed by the use, twice daily, of a 0.12% chlorhexidine, commercially available, mouth rinse.
2. The control group will use three times daily a provided manual toothbrush with the placebo toothpaste (identical to the test tooth paste, but without the active ingredients), followed by the use, twice daily, of a 0.12% chlorhexidine mouth rinse,

All subjects will be masked to their group allocation and will receive their assigned products kit containing: a manual toothbrush (Vitis Suave, Dentaid, Barcelona, Spain), the test or placebo toothpaste, and the mouth rinse with dose caps. They will be instructed to brush with the toothpaste (the amount of a pee size) for 2 minutes, twice daily, and then rinse for 30 seconds with 15 mL of the mouth rinse, twice daily. Standardized instructions will be given for mechanical supragingival biofilm control, including the use of interdental brushes (Interprox®, Dentaid, Barcelona, Spain). Each subject will receive standardized verbal and written instructions on how to use the assigned products.

2-week visit (final visit, RCT #1; initial visit, RCT #2) Two weeks after the second session of subgingival instrumentation, an oral examination will be performed to evaluate possible adverse effect, and dental plaque index will be recorded. Clinical photographs will be also taken to assess staining (four, for sextants 2 and 5, for buccal and palatal surfaces).

The subjects will be asked about the occurrence of any adverse effects. A questionnaire on product usage and perceptions (PROMs), dietary habits and compliance with product use will be filled by the patients. The study coordinator will collect the empty and unused tubes and bottles. Subjects will be provided with a new kit containing the necessary assigned products.

Subjects will stop using the mouth rinse, and will start the second RCT, being randomized again, within each group of the first RCT, to the placebo or test toothpaste. Thus, at the 2-week visit, half of each group will continue with the same toothpaste and the other half will change toothpaste, creating four different groups, when considering both RCTs: group control-control, group control-test, group test-control, group test-test)

4-week visit (final visit, RCT #2) After 4 weeks, a comprehensive oral examination will be performed, including the assessment of clinical variables. The subjects will be asked about the occurrence of any adverse effects and the study coordinator will collect the empty and unused tubes. A new questionnaire on product usage and perceptions (PROMs), dietary habits and compliance with product use will be filled by the patients.

Clinical photographs (four, for sextants 2 and 5, for buccal and palatal surfaces) will be also taken to assess staining. All subjects will be provided with a professional dental prophylaxis at the end of the study.

Eligibility Criteria:
Inclusion Criteria:

* 30-69 years old.
* Periodontitis patients, in stages I-III, requiring steps 1 and 2 of periodontal treatment including full-mouth subgingival instrumentation.
* Systemically healthy, following the criteria of the American Society of Anesthesiologists (ASA), for patients ASA type I or II (see also exclusion criteria).
* Presence of at least three evaluable teeth in each quadrant.
* No orthodontic banding or removable prosthesis.
* Subjects willing to participate and comply with the requirements of the study.

Exclusion Criteria:

* Acute periodontal conditions.
* Antibiotic intake within the previous month.
* Chronic use of analgesic or anti-inflammatory drugs.
* Pregnant women.
* Any adverse medical history (diabetes, osteoporosis, immunosuppression...) or long-term medication (chemotherapy and immunosuppression treatment; pharmacological treatment associated with gingival overgrowth such as the use of phenytoin, phenobarbital, lamotrigine, vigabatrin, ethosuximide, topiramate, primidone, nifedipine, amlodipine, verapamil, cyclosporine) influencing gingival conditions.
* Conditions which require antibiotic prophylaxis (infectious endocarditis, cardiac valve prosthesis...).