Omega-3 Plus Low-dose Aspirin Daily Supplementation in Non-surgical Therapy to Treat Aggressive Periodontitis
Condition: Aggressive Periodontitis
MeSH terms: Periodontitis; Aggressive Periodontitis; Aggression
Study type: Interventional
Phase: Phase 2/Phase 3

Summary: 
      The aim of this randomized controlled clinical trial of superiority will be to evaluate the
      effect of 3 g of omega-3 polyunsaturated fatty acids and 100 mg of aspirin daily
      supplementation over a period of 180 days as adjunct to non-surgical therapY of patients with
      generalized aggressive periodontitis. Probing depth, clinical attachment level, gingival
      index and concentration of microorganisms and cytokines at baseline, 3, and 6 12 months after
      the procedure will be evaluated.
    

Detailed description: 
      The study methodology is according to CONSORT-STATEMENT 2010 for randomized controlled
      clinical trials.

      Study Design The study is designed as a prospective, interventional, parallel, blinded,
      randomized, controlled clinical trial of superiority.

      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. Patients
      will fill a healthy history questionnaire to ensure that they are medically qualified for
      participate in this study. Based on the power calculation for this study, a population of 38
      patients will be included. Considering α of 5% and 10% β-type error (90% power) to detect a
      difference of at least 1 mm in probing depth reduction of pockets ≥ 5 mm between groups, for
      a standard deviation of 0.94 from a previous study evaluating different antimicrobials in the
      treatment of GAgP (Xajigeorgiou et al., 2006), 19 patients will be needed in each group.

      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 groups according to a computer-generated list. The
      allocation will be implemented by an investigator (NC) who was not directly involved in the
      examination or treatment procedures.

      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. Immediately before the mechanical therapy,
      patients will be allocated in one of the two treatment protocols:

      Test group (n = 19): FMUD + 3 g of omega-3 polyunsaturated fatty acids and 100 mg of aspirin
      daily supplementation over a period of 180 days; Control group (n = 19): FMUD + placebo
      pills.

      All patients will start taking the pills immediately before of the FMUD session.

      Microbiological evaluation Subgingival microbiological samples will be collected at the
      baseline, 3 and 6 months after therapy. The site will be isolated with a sterile cotton
      roller and supragingival biofilm will be carefully removed with periodontal curettes and a
      sterile paper will be inserted into the periodontal pocket for 30 s (Hartoth et al., 1999).
      The sample will be stored in sterile microtubes. The samples will then be lyophilized and
      sent to the Department of Periodontology at the University of Florida, where the samples will
      be analyzed.

      Evaluation of cytokines For the analysis of immunological changes, crevicular gingival fluid
      (CGF) will be collected at baseline, 3 and 6 months after treatment. Each site will be
      isolated with a sterile cotton roller and the supragingival biofilm will be removed. After
      this, the CGF will be collected with Periopaper strips (Periopaper, Oraflow, Plainview, NY,
      USA), inserted in the pocket for 15 seconds. The volume of collected fluid will be measured
      (Periotron 8000, Oraflow). The Periopaper strips will be stored in a sterile tube containing
      300μl of phosphate saline (PBS) with 5% Tween-20 and stored in a freezer at -20 ° C until the
      multiplex test. The level of the following cytokines will be measured in the CGF: interferon
      (IFN) -γ, interleukins (IL) -10, -1β, -4, -6, -8, tumor necrosis factor (TNF) -α, macrophage
      inflammatory protein 1α (MIP1α), 1α monocyte chemotactic protein (MCP-1α). The 10-plex high
      sensitivity kit (Millipore Corporation, Billerica, MA, USA) will be used according to the
      manufacturer's instruction and analyzed using the MAGpixTM platform (MiraiBio, Alameda, CA,
      USA). Samples will be analyzed individually (each pocket separately) and the concentrations
      will be calculated using a standard 5-parameter curve in the Xponet program (Millipore
      Corporation). The concentration of each marker will be given in pg / ml. All analysis of
      cytokine concentrations will be done in duplicate.

      Statistical analysis Two analyzes will be performed: Per Protocol and Intention-to-treat
      (Moher, 2010; Gupta, 2011; Day, 2008). For each of them, mean and standard deviation will be
      calculated in each of the parameters. Full-mouth PI, GI, PD, CAL, and GR will be submitted to
      the Shapiro-Wilk test to evaluate the distribution of these data, and then subjected to the
      variance test for both intra- and intra-group comparison. In addition, the number of pockets
      ≥ 5mm, the frequency of closure of these pockets, the mean reduction in PS and the gain in
      CAL of these pockets will be assessed before and after the therapy by performing intra- and
      inter-group analyzes.

      The concentration of each cytokine will be analyzed by test of variance for intra and
      intergroup comparison.
    

Intervention name(s): Omega-3 polyunsaturated fatty acids; Aspirin; Placebo; Full-mouth ultrasonic debridement
Intervention type(s): Dietary Supplement; Drug; Other; Procedure
Intervention description(s): 3 g of omega-3 polyunsaturated fatty acids daily supplementation over a period of 180 days; 100 mg of aspirin daily supplementation over a period of 180 days; Placebo pills over a period of 180 days; Full-mouth ultrasonic debridement will be performed in order to treat diseased sites
Other intervention name(s): Fish oil; acetylsalicylic acid; Periodontal debridement
Intervention MeSH terms: Aspirin
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Full-mouth ultrasonic debridement; Aspirin; Omega-3 polyunsaturated fatty acids; Non-surgical therapy