Plaque Formation Rate and Toothpaste
Condition: Chronic Periodontitis
MeSH terms: Periodontitis; Chronic Periodontitis
Study type: Interventional

Summary: 
      This 12-week prospective, randomized, double-blind, two-center trial evaluated the impact of
      a microcrystalline zinc-hydroxyapatite (mHA) dentifrice on plaque formation rate (PFR) in
      periodontitis patients. The investigators hypothesized that mHA precipitates cause delayed
      plaque development when compared to a fluoridated control (AmF/SnF2), and therefore would
      improve periodontal health.
    

Detailed description: 
      Study Objectives and Purpose The purpose of this study is to assess the clinical efficacy of
      a new dentifrice, containing carbonate/hydroxyapatite nanocrystals (BioRepair®, Kurt Wolff,
      Bielefeld, Germany), in subjects suffering from severe gingivitis and/or mild to moderate
      chronic periodontitis and receiving non-surgical periodontal therapy. Clinical efficacy will
      be evaluated regarding clinical and microbiological parameters and compared to the use of a
      zinc-fluoride containing dentifrice (Meridol®, GABA, Lörrach, Germany) serving as a positive
      control.

      Research Questions

      This three-month clinical trial is conducted to answer the following research questions:

      Primary Question

        1. Is there a difference in de novo plaque formation as measured by the Plaque Formation
           Rate Index (Axelsson 1991) between subjects using the new carbonate/hydroxylapatite
           nanocrystal dentifrice and those using the established zinc-fluoride containing control
           dentifrice? Secondary Questions

        2. Are there differences between subjects using the two dentifrices with respect to their
           subjective perception of therapy?

        3. Are there differences between the two dentifrices with respect to the following
           periodontal measurements: change of full mouth plaque scores (O'Leary Plaque Control
           Record, O'Leary 1972), gingival index (Löe 1967), change of pocket probing depths
           (PPD's), and the percentage of sites with attachment gain of ≥ 2 mm?

        4. Are there qualitative and quantitative changes regarding the composition of the oral
           microflora?

      Study design The investigation is designed as a double blind, parallel group, and randomized
      trial over a 3-months period (primary endpoint). Secondary endpoints are not scheduled.
      Seventy-five subjects will be enrolled in this four-visit study; visits 1-4 are required for
      each subject. Test and control group subjects will be treated following identical therapy
      protocols, except for the dentifrice. Participating study centers will be the Department of
      Periodontology at the University of Münster and the Department of Periodontology at the
      University of Würzburg.

      Subject Registration and Randomization Subjects that fulfil all the inclusion criteria, do
      not meet any exclusion criteria, and have signed the informed consent will be registered into
      the study by the centers Münster or Würzburg (visit 1). At visit 2 study subjects will be
      randomly assigned to the test group using the carbonate/hydroxyapatite nanocrystal dentifrice
      or the control group using a zinc-fluoride containing dentifrice. Patient randomization is
      warranted by using a randomization list (block randomization with 4 subjects per block).
      Designation of a study subject as a smoker/non-smoker will be based on recording
      carbonmonoxide concentration in exhaled air (non-smoker: less than 3 ppm CO in exhaled air;
      smoker: equal to or more than 3 ppm).

      Treatment of subjects At visit 1 ("Screening/Recruitment") all subjects are informed about
      the projected trial. If subjects are willing to participate, they receive periodontal
      screening examination (PSI) and medical history is asked. At visit 2 ("Baseline", consist of
      two appointments at intervals of 24 hours) within the first appointment, subjects are
      randomized and periodontal parameters are examined. The blinded packages of different
      dentifrices are dispensed to the subjects. At the end, the subjects receive routine
      supragingival scaling with sonic scalers and polishing with an air powder device (glycin
      powder). Subjects are instructed to abstain from oral hygiene for the next 24 hours. At the
      end, subjects fill out the two questionnaires. At the second appointment, plaque formation
      rate is examined and subjects are instructed to brush with their already used toothbrush for
      2 minutes at least twice per day at home.

      Four weeks after "Baseline" at visit 3 ("Treatment", consist of two appointments at intervals
      of 24 hours), periodontal parameters are examined and all subjects receive full mouth supra-
      and subgingival debridement in two sessions on two consecutive days. Debridement is performed
      with sonic scalers using micro tips under local anesthesia and polishing is performed with an
      air powder device. Subjects are instructed to abstain from oral hygiene for the next 24
      hours. At the second appointment, plaque formation rate is examined, all subjects receive
      full mouth supra- and subgingival debridement, and are instructed to brush with their already
      used toothbrush for 2 minutes at least twice per day at home. Two months after "Treatment" at
      visit 4 ("Reevaluation", consist of two appointments at intervals of 24 hours) periodontal
      parameters are examined and all subjects receive full mouth supragingival debridement in one
      session. Subjects are instructed to abstain from oral hygiene for the next 24 hours. At the
      second appointment, plaque formation rate is examined, all subjects receive full mouth
      supragingival debridement. Subjects return the dentifrice packages.

      Over the course of the study no medication except the dentifrice or local anesthesia is
      administered. During the trial, subjects are not permitted to undergo advanced periodontal
      treatment (i.e. periodontal surgery) or to receive drugs influencing periodontal health.

      Clinical Examinations After assessing the plaque and the gingival index (O'Leary 1972, Löe
      1967) clinical measurements of full mouth pocket probing depths (PPD), bleeding on probing
      (BOP), gingival recessions (GR), and furcation involvement are taken. All measurements,
      except for furcation involvement, are taken at six sites per tooth (mesiobuccal, mid-buccal,
      distobuccal, mesiolingual, mid-lingual and distolingual). Measurements of PPD, BOP, and GR
      are performed using a standard Florida Probe® handpiece (Florida Probe Corp., Gainsville, FL,
      USA). Clinical measurements are taken at baseline, after 4 weeks, and after 3 months (visits
      2a, 3a, and 4a). Smoking habits are determined by an objective chairside measurement of
      carbon monoxide concentration in exhaled air (Bedfont-Smokerlyzer®, Bedfont, UK) at visits 1
      through 4. Intraoral radiographs and photographs are taken at baseline.

      Specification of Psychological Assessments At visits 2a and 4a patients are asked to complete
      the Oral Health Impact Profile - German Version (OHIP-G 49) and the German version of the
      Client Satisfaction Questionnaire (ZUF-8) as a standardized instrument used to measure health
      outcome.

      Oral Health Impact Profile - German Version (OHIP-G 49) The original English version of the
      questionnaire was developed by Slade and Spencer (1994). The German translation and
      validation of the instrument was performed by John et al. (2002). The OHIP-G 49 contains 49
      items that address specific problems of oral health, e.g., "problems with chewing of food" or
      "pain in the gums". Each item is assessed on a five-point scale (0: never to 4: very often).
      A sum score of all of the items is calculated as an indicator for current oral health. The
      completion of the questionnaire takes about ten minutes.

      ZUF-8 The patients´ satisfaction with the treatment is evaluated by means of the Fragebogen
      zur Patientenzufriedenheit (ZUF-8, Schmidt et al. 1989) which represents the German version
      of the Client Satisfaction Questionnaire (CQS, Attkisson & Zwick 1982).

      Microbiological Examination For microbiological analysis, pooled subgingival plaque samples
      are taken from four different teeth with at least one site with PPDs of ≥ 4 mm from each
      study subject. The pooled subgingival plaque sample is collected in a transport tube
      containing 500 µl Ringer-Glycerin-Solution. The pooled samples are at once taken to the
      laboratory for analysis or stored in liquid nitrogen.

      Supragingival plaque is collected from four sites per sample tooth. From the buccal and
      lingual sites samples are taken using Periotron© adapted to the tooth surface to collect
      dental plaque from the area near the gingival margin. Interproximal, supragingival plaque
      samples are collected by inserting a sterile paperpoint horizontally in buccal to lingual
      direction near the gingival margin. Samples from buccal/lingual and from interproximal sites
      are pooled respectively (two pooled samples from each subject per visit 2a, 3a, 4a) in a
      seperate transport tube containing 500 µl Ringer-Glycerin-Solution. The pooled samples are at
      once taken to the laboratory for analysis or stored in liquid nitrogen.

      Sample teeth are randomly selected at baseline as shown in Fig. 2 to assure equal
      distribution throughout the mouth, and remain the same over the course of the study. The
      whole bacterial counts are quantified by culture at study visits 2a, 3a, and 4a.

      Laboratory Processing, Microbiological Analysis After subgingival plaque sampling, the
      samples are taken immediately in the laboratory for further processing or stored in liquid
      nitrogen until the study is finished. After finishing the trial they will be carried to
      Münster. For transport they are stored in carbon dioxide snow and are stored in liquid
      nitrogen in the laboratory in Münster again. The pooled samples are sonicated for 10 seconds
      (Sonotex RK 82, Bandelin Electronic AG, Berlin, Germany) and diluted in tenfold steps. 0.1 ml
      of the undiluted suspension and 0.1 ml aliquots of the dilutions are spread on different
      culture media. In parallel supragingival plaque samples are spread on CDC agar and are stored
      in an aerobe atmosphere at 37 degree above zero overnight.

      For quantitative enumeration the undiluted and diluted suspensions are spread on
      non-selective blood agar (CDC agar) plates containing 5% defibrinated sheep blood
      supplemented with 5mg/l hemin (Merck, Darmstadt, Germany), 1 mg/l vitamin K1, and 10 mg/l
      N-acetylmuramine acid (NAM). NAM is supplemented for cultivation of T. forsythensis. The
      plates are incubated in an atmosphere containing N2 (85%), H2 (10%), and CO2 (5%) for 7 days.
      Total cultivable counts are assessed for each of the plaque samples. The evaluation of pooled
      plaque samples on CDC agar and the total cultivable counts are reported quantitatively as
      colony forming units (CFU/ml). In further investigation the present of specific periodontal
      pathogens will be evaluated.
    

Intervention name(s): AmF/SnF2; mHA
Intervention type(s): Other; Other
Intervention description(s): AmF/SnF2 dentifrice used twice daily for 2 minutes for 12 weeks; microcrystalline zinc-hydroxyapatite (mHA) dentifrice dentifrice used twice daily for 2 minutes for 12 weeks.
Other intervention name(s): Meridol®, GABA, Lörrach, Germany; BioRepair® toothpaste, Kurt Wolff GmbH, Bielefeld, Germany.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Supportive Care