title: Antimicrobial photodynamic therapy combined with periodontal treatment for metabolic control in patients with type 2 diabetes mellitus: study protocol for a randomized controlled trial.
abstract: BACKGROUND
  The relationship between diabetes mellitus (DM) and periodontal disease is bidirectional. DM is a predisposing and modifying factor of periodontitis, which, in turn, worsens glycemic control and increases proteins found in the acute phase of inflammation, such as C-reactive protein. The gold standard for the treatment of periodontal disease is oral hygiene orientation, scaling and planing. Moreover, systemic antibiotic therapy may be employed in some cases. In an effort to minimize the prescription of antibiotics, photodynamic therapy (PDT) has been studied as an antimicrobial technique and has demonstrated promising results. The aim of the proposed study is to determine whether PDT as a complement to periodontal therapy (PT) is helpful in the metabolic control of individuals with type 2 diabetes and the reduction of acute-phase inflammatory markers.
  
  
  METHODS
  The patients will be randomized using a proper software program into two groups: 1) PT + placebo PDT or 2) PT + active PDT. All patients will first be examined by a specialist, followed by PT performed by two other healthcare professionals. At the end of each session, PDT (active or placebo) will be administered by a fourth healthcare professional. The following will be the PDT parameters: diode laser (660 nm); power output = 110 mW; exposure time = 90 s per point (9 J/point); and energy density = 22 J/cm(2). The photosensitizer will be methylene blue (50 μg/mL). The patients will be re-evaluated 15, 30, 90 and 180 days after treatment. Serological examinations with complete blood count, fasting glucose, glycated hemoglobin and salivary examinations to screen for tumor necrosis factor alpha, interleukin 1, interleukin 6, ostelocalcin, and osteoprotegerin/RANKL will be performed at each evaluation. The data will be statistically evaluated using the most appropriate tests.
  
  
  CONCLUSIONS
  The results of this study will determine the efficacy of photodynamic therapy as an adjuvant to periodontal treatment in diabetic patients.
  
  
  BACKGROUND
  The protocol for this trial was registered with Clinical Trials registration number NCT01964833 on 14 October 2013.
authors.affiliation: Program in Biophotonics Applied to Health Sciences, University Nove de Julho, UNINOVE, Rua Vergueiro 235/249 - Liberdade, São Paulo, SP, 01504-001, Brazil. erikacatalani@ig.com.br.
authors.forename: Erika Elisabeth
authors.initials: EE
authors.lastname: Evangelista
authors.affiliation: Program in Biophotonics Applied to Health Sciences, University Nove de Julho, UNINOVE, Rua Vergueiro 235/249 - Liberdade, São Paulo, SP, 01504-001, Brazil. cristianepatologia@uninove.br.|School of Medicine, Nove de Julho University UNINOVE, Rua Vergueiro 235/249 - Liberdade, São Paulo, SP, 01504-001, Brazil. cristianepatologia@uninove.br.|Program in Rehabilitation Science, Nove de Julho University - UNINOVE, Rua Vergueiro 235/249 - Liberdade, São Paulo, SP, 01504-001, Brazil. cristianepatologia@uninove.br.
authors.forename: Cristiane Miranda
authors.initials: CM
authors.lastname: França
authors.affiliation: Program in Biophotonics Applied to Health Sciences, University Nove de Julho, UNINOVE, Rua Vergueiro 235/249 - Liberdade, São Paulo, SP, 01504-001, Brazil. priscilaveni@hotmail.com.|School of Dentistry, Nove de Julho University UNINOVE, Rua Vergueiro 235/249 - Liberdade, São Paulo, SP, 01504-001, Brazil. priscilaveni@hotmail.com.
authors.forename: Priscila
authors.initials: P
authors.lastname: Veni
authors.affiliation: Program in Biophotonics Applied to Health Sciences, University Nove de Julho, UNINOVE, Rua Vergueiro 235/249 - Liberdade, São Paulo, SP, 01504-001, Brazil. tamires.oliveira@uninove.edu.br.
authors.forename: Tamires
authors.initials: T
authors.lastname: de Oliveira Silva
authors.affiliation: Program in Biophotonics Applied to Health Sciences, University Nove de Julho, UNINOVE, Rua Vergueiro 235/249 - Liberdade, São Paulo, SP, 01504-001, Brazil. rafamoredo@hotmail.com.
authors.forename: Rafael Moredo
authors.initials: RM
authors.lastname: Gonçalves
authors.affiliation: School of Dentistry, Nove de Julho University UNINOVE, Rua Vergueiro 235/249 - Liberdade, São Paulo, SP, 01504-001, Brazil. vecarvalho@gmail.com.
authors.forename: Verônica Franco
authors.initials: VF
authors.lastname: de Carvalho
authors.affiliation: Program in Biophotonics Applied to Health Sciences, University Nove de Julho, UNINOVE, Rua Vergueiro 235/249 - Liberdade, São Paulo, SP, 01504-001, Brazil. amdeana@gmail.com.
authors.forename: Alessandro Melo
authors.initials: AM
authors.lastname: Deana
authors.affiliation: Program in Biophotonics Applied to Health Sciences, University Nove de Julho, UNINOVE, Rua Vergueiro 235/249 - Liberdade, São Paulo, SP, 01504-001, Brazil. kristianneporta@uninove.br.|School of Dentistry, Nove de Julho University UNINOVE, Rua Vergueiro 235/249 - Liberdade, São Paulo, SP, 01504-001, Brazil. kristianneporta@uninove.br.|Program in Rehabilitation Science, Nove de Julho University - UNINOVE, Rua Vergueiro 235/249 - Liberdade, São Paulo, SP, 01504-001, Brazil. kristianneporta@uninove.br.
authors.forename: Kristianne P S
authors.initials: KP
authors.lastname: Fernandes
authors.affiliation: Program in Biophotonics Applied to Health Sciences, University Nove de Julho, UNINOVE, Rua Vergueiro 235/249 - Liberdade, São Paulo, SP, 01504-001, Brazil. raquel.mesquita@gmail.com.|School of Medicine, Nove de Julho University UNINOVE, Rua Vergueiro 235/249 - Liberdade, São Paulo, SP, 01504-001, Brazil. raquel.mesquita@gmail.com.|Program in Rehabilitation Science, Nove de Julho University - UNINOVE, Rua Vergueiro 235/249 - Liberdade, São Paulo, SP, 01504-001, Brazil. raquel.mesquita@gmail.com.
authors.forename: Raquel A
authors.initials: RA
authors.lastname: Mesquita-Ferrari
authors.affiliation: School of Medicine, Nove de Julho University UNINOVE, Rua Vergueiro 235/249 - Liberdade, São Paulo, SP, 01504-001, Brazil. camacho@uninove.br.|Medical Sciences, Nove de Julho University - UNINOVE, Rua Vergueiro 235/249 - Liberdade, São Paulo, SP, 01504-001, Brazil. camacho@uninove.br.
authors.forename: Cleber P
authors.initials: CP
authors.lastname: Camacho
authors.affiliation: Program in Biophotonics Applied to Health Sciences, University Nove de Julho, UNINOVE, Rua Vergueiro 235/249 - Liberdade, São Paulo, SP, 01504-001, Brazil. sandrakalil@uninove.br.|School of Dentistry, Nove de Julho University UNINOVE, Rua Vergueiro 235/249 - Liberdade, São Paulo, SP, 01504-001, Brazil. sandrakalil@uninove.br.|Program in Rehabilitation Science, Nove de Julho University - UNINOVE, Rua Vergueiro 235/249 - Liberdade, São Paulo, SP, 01504-001, Brazil. sandrakalil@uninove.br.
authors.forename: Sandra Kalil
authors.initials: SK
authors.lastname: Bussadori
authors.affiliation: Program in Biophotonics Applied to Health Sciences, University Nove de Julho, UNINOVE, Rua Vergueiro 235/249 - Liberdade, São Paulo, SP, 01504-001, Brazil. leclimaco@hotmail.com.
authors.forename: Letícia Heineck
authors.initials: LH
authors.lastname: Alvarenga
authors.affiliation: Program in Biophotonics Applied to Health Sciences, University Nove de Julho, UNINOVE, Rua Vergueiro 235/249 - Liberdade, São Paulo, SP, 01504-001, Brazil. pratesra@uninove.br.|School of Dentistry, Nove de Julho University UNINOVE, Rua Vergueiro 235/249 - Liberdade, São Paulo, SP, 01504-001, Brazil. pratesra@uninove.br.
authors.forename: Renato Araujo
authors.initials: RA
authors.lastname: Prates
mesh_terms: D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D001938:Brazil; D002908:Chronic Disease; D002985:Clinical Protocols; D003131:Combined Modality Therapy; D012534:Dental Scaling; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D004311:Double-Blind Method; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood*; D008751:Methylene Blue / Q000009:adverse effects / Q000627:therapeutic use*; D010510:Periodontal Diseases / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000382:microbiology; D010778:Photochemotherapy / Q000009:adverse effects / Q000379:methods*; D017319:Photosensitizing Agents / Q000009:adverse effects / Q000627:therapeutic use*; D012107:Research Design; D016745:Root Planing; D012463:Saliva / Q000378:metabolism*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D006442:Glycated Hemoglobin; D018836:Inflammation Mediators; D008751:Methylene Blue; D017319:Photosensitizing Agents; C517652:hemoglobin A1c protein, human