Periodontal Debridement Associated With Systemic Antibiotics and Single/Repeated PDT to Treat Aggressive Periodontitis
Condition: Aggressive Periodontitis, Generalized
MeSH terms: Periodontitis; Aggressive Periodontitis; Aggression
Study type: Interventional
Phase: Phase 2/Phase 3

Summary: 
      The aim of this project is to compare the efficacy and the local effect of the association of
      single or repeated application of photodynamic therapy (PDT) with antibiotic agents using
      Amoxicillin + Metronidazole or Clarithromycin in the treatment of patients with Generalized
      Aggressive Periodontitis (GAgP).
    

Detailed description: 
      The study methodology is according to CONSORT-STATEMENT 2010 and SPIRIT 2013 for randomized
      controlled clinical trials.

      Study Design

      The study is designed as a prospective, interventional, parallel, blinded, randomized,
      controlled clinical trial aimed to compare the efficacy and the local effect of the
      association of single or repeated application of photodynamic therapy (PDT) with antibiotic
      agents using Amoxicillin + Metronidazole or Clarithromycin in the treatment of patients with
      Generalized Aggressive Periodontitis (GAgP).

      Source of data

      The population of this study will be recruited among patients referred to the Science and
      Technology Institute (ICT) - São José dos Campos, College of Dentistry. Each one of 46
      patients will have three pockets with probing depth and loss of clinical attachment level ≥5
      mm and bleeding on probing not located at furcation sites randomly chosen.

      Power calculation

      A population of 46 patients (138 periodontal pockets, 3 per patient) that meet the
      pre-established criteria will be considered. Considering α = 5% and a β = 5% to detect a
      difference of 1 mm between groups in probing depth reduction of pockets ≥5 mm, for a standard
      deviation of 0.8 mm, 14 patients will be needed in each group. With a sample of 46 patients
      (138 pockets), the study will have a power greater than 95%.

      Clinical Parameters

      All clinical parameters will be assessed by a single blinded, trained and calibrated examiner
      (CFA) before periodontal therapy (baseline) and at 3 and 6 months after using a manual probe.
      Measurements will be done at six sites per tooth (mesiobuccal, buccal, disto-buccal,
      distolingual, lingual, and mesiolingual) in all teeth, except third molars.

      The following clinical parameters will be evaluated: 1) Full-mouth plaque index (FMPI); 2)
      Bleeding on probing (BoP); 3) Probing depth (PD): distance from the bottom of sulcus/pocket
      to gingival margin; 4) Gingival recession (GM): distance from the free gingival margin to
      cement-enamel junction (CEJ); 5) Clinical attachment level (CAL): distance from bottom of
      sulcus/pocket to the CEJ. The CEJ will be identified by careful probe on cervical area.

      Calibration and Randomization

      Initially, a total of ten patients presenting with GAgP will be selected. The designated
      examiner (CFA) will measure CAL and PD in all patients twice within 24 hours, with an
      interval of ≥ 1 hour between examinations. Then, the measures will be submitted to intraclass
      correlation test and the examiner will be judged calibrated if reaches 90% agreement.

      Patients will be allocated into two antibiotic groups (that will receive Amoxicillin +
      Metronidazole or Clarithromycin) according to a computer-generated list. The allocation will
      be implemented by an investigator (NCCS) who was not directly involved in the examination or
      treatment procedures. All medication will be prepared and encased in identical opaque coded
      bottles by a compounding pharmacy. The same person outside the project will generate a random
      sequence regarding the type of PDT application for each patient, for the three previously
      selected pockets (single or repeated application of PDT or control), which will be revealed
      shortly after the periodontal debridement session.

      Treatment Protocols

      All patients will be treated with periodontal therapy through of the one-stage, full mouth,
      ultrasonic debridement (FMUD). In a single session, patients will receive local anesthesia
      and periodontal debridement with ultrasound equipment (Cavitron - Dentsply EUA) and
      subgingival tips (UI25KSF10S, Hu-Friedy). All diseased sites will be instrumented in this one
      session. The debridement session will be performed by a single experienced and trained
      periodontist (NA), different from the examiner (ca). Immediately before the mechanical
      therapy, patients will be allocated in one of the two treatment protocols: Clarithromycin
      (CLM) group (n = 22): FMUD + CLM 500 mg bid, for 7 days or Amoxicillin (AMX) + metronidazole
      (MET) group (n = 22): FMUD + (AMX 500 mg tid + MET 400 mg tid, both for 7 days. All patients
      will start taking the pills immediately before the FMUD session.

      After periodontal debridement (PD), two periodontal pockets from each patient will receive
      the proposed PDT protocols to assist the decontamination of diseased sites. One pocket will
      receive a single application of PDT (sPDT) (baseline only) and the other will receive
      repeated application of PDT (rPDT). After subgingival irrigation with saline solution to wash
      the pocket, the photosensitizer (methylene blue 10 mg / mL) will be applied to the bottom of
      the pocket by buccal side until it is completely filled. After one minute, the pocket will be
      washed with water and exposed to low-level laser (TheraLase - Brazil), with a corresponding
      optical fiber of 600 um diameter, which will be inserted into the pocket. A 660 nm wavelength
      with a power of 60 milliwatts and a dose of 129 J / cm2 will be used for one minute. The same
      procedure will be repeated by lingual site, totaling two minutes of application per pocket.
      The repeated application protocol will consist of 5 applications on different days, performed
      on the day of periodontal treatment (baseline - 0), 1, 2, 7 and 14 days after. Thus, the
      following comparative groups will be formed, totaling 138 pockets:

      PD + (AMX + MET) (n = 23): periodontal pockets that will receive periodontal debridement
      associated with Amoxicillin + Metronidazole;

      PD + CLM (n = 23): periodontal pockets that will receive periodontal debridement associated
      with the use of Clarithromycin;

      PD + (AMX + MET) + sPDT (n = 23): periodontal pockets that will receive periodontal
      debridement associated with Amoxicillin + Metronidazole and single application of PDT; PD +
      CLM + sPDT (n = 23): periodontal pockets that will receive periodontal debridement associated
      with the use of Clarithromycin and single application of PDT;

      PD + (AMX + MET) + rPDT (n = 23) : periodontal pockets that will receive periodontal
      debridement associated with Amoxicillin + Metronidazole and repeated application of PDT;

      PD + CLM + rPDT (n = 23): periodontal pockets that will receive periodontal debridement
      associated with Clarithromycin and repeated application of PDT

      Statistical analysis

      Mean and standard deviation will be calculated for each parameter. The normal distribution of
      the data will be analyzed by Shapiro-Wilk test. Data from clinical measurements will be
      subjected to analysis of variance (repeated measures) for inter and intra-group comparison.
    

Intervention name(s): Full-mouth ultrasonic debridement; Amoxicillin 500mg; Metronidazole 400mg; Clarithromycin 500mg; Single application of PDT; Repeated application of PDT
Intervention type(s): Procedure; Drug; Drug; Drug; Procedure; Procedure
Intervention description(s): Full-mouth ultrasonic debridement will be performed in order to treat diseased sites; Administration of Amoxicillin 500mg tid for 7 days; Administration of Metronidazole 400mg tid for 7 days.; Administration of Clarithromycin 500mg bid for 7 days; Single application of photodynamic therapy (PDT) at day 0.; Repeated application of photodynamic therapy (PDT) at 0, 1, 2, 7 and 14 days post-operatively.
Other intervention name(s): Periodontal debridement; Amoxil; Flagyl; Biaxin
Intervention MeSH terms: Amoxicillin; Metronidazole; Clarithromycin
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary purpose: Treatment
Keywords: Full-mouth ultrasonic debridement; Clarithromycin; Amoxicillin; Metronidazole; Antimicrobial therapy; Photodynamic therapy; Low-level laser therapy