Clinical trial NCT01964833: PDT and Periodontal Treatment in DMT2 Patients
Official title: Combination of Photodynamic Therapy and Periodontal Treatment in Patients With Type 2 Diabetes Mellitus: Randomized, Double-blind Clinical Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Periodontitis
Diabetes Mellitus Type 2
Keywords: clinical trial
DMT2
periodontitis
PDT
Lead sponsor: University of Nove de Julho
Sponsor class: OTHER
First posted: 2013-10-17
Enrollment: 44
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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. 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. 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 sham) 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 seconds per point (9 J/point); and energy density = 22 J/cm2. The photosensitizer will be methylene blue (50 µg/mL). The patients will be re-evaluated 15, 30, 90 and 180 days after treatment. Serological exams with complete blood count, fasting glucose, glycated hemoglobin and crevicular fluid exams to screen for tumor necrosis factor alpha, interleukin 1, interleukin 6, osteocalcin, osteoprotegerin/RANKL will be performed at each evaluation. At baseline and 180 day periapical radiographs will be performed to evaluate the alveolar bone crest level. The data will be statistically evaluated using the most appropriate tests.

Detailed description: Randomization of the patients to the different groups will be performed with the appropriate software program. Only the lead researcher will have access to the randomization list. Allocation to the two groups will be carried out in blocks of four.

The patients will be sent to Operator A for the periodontal exam. Without knowledge of the results of this exam, the patients will be treated by Operators B and C for periodontal treatment, which will involve oral hygiene instructions as well as supra-gingival and sub-gingival scaling and planing in up to four sessions. At the end of each session, the patients will be sent to Operator D, who will administer either placebo or active PDT based on the content of the sealed envelope. Thus, both the patients and operator in charge of the periodontal exams will be blinded to the PDT protocol (double-blind study).

Fasting blood sugar and glycated hemoglobin exams will be performed at baseline as well as 15, 30, 90 and 180 days after the completion of treatment. All exams will be carried out at the same laboratory affiliated with the university.

The clinical periodontal exams will be performed by a single examiner specialized in periodontics, who will evaluate six regions of each tooth with a 15-mm probe (North Carolina model, Hu-Friedy, Chicago, IL, USA). The following aspects will be recorded: plaque index, bleeding upon probing, probing depth, gingival recession and attachment loss (Armitage, 2004). Evaluations will be carried out performed at baseline (prior to initial treatment) as well as 15, 30, 90 and 180 days after the completion of treatment.

Patients will receive periodontal treatment and photodynamic therapy (active or sham depending on the allocation).

Crevicular fluid will be collected from the previously defined sites with a probing depth equal to or greater than 4 mm that will receive treatment. Collection will be performed with relative isolation using cotton rolls following the removal of supra-gingival plaque with periodontal curettes and air drying for five seconds. Absorbent paper strips (PerioPaper, ProFlow Inc., Amityville, NY, USA) will be individually inserted into each site for 30 seconds (Rudin et al., 1970). The collections will be performed by a single researcher. The volume of crevicular fluid samples will be measured using the Periotron 8000 micro-moisture meter (Oraflow Inc., NY, USA). The samples will then be placed in duly identified sterile plastic microtubes, temporarily stored in dry ice and subsequently stored in a freezer at -80 ºC

Eligibility criteria: Inclusion Criteria:

1. Compensated type 2 diabetes mellitus or with adequate control based on the criteria of the Brazilian Society of Diabetes (SBD, 2012);
2. Chronic periodontitis (AAP, 2001);
3. Presence of at least 15 teeth and at least four teeth with bleeding upon probing and probing depth greater than 4 mm;
4. Aged 18 years or older;
5. Under follow up with an endocrinologist.

Exclusion Criteria:

1. Uncompensated diabetes, based on SBD criteria;
2. Smoking habit in 12 months prior to treatment;
3. Anemia;
4. Active cancer;
5. Current pregnancy;
6. History of antibiotic therapy in previous six months;
7. History of anti-inflammatory therapy in previous three months;
8. Clotting disorder (use of anti-coagulant, presence of liver disease, thrombocytopenia and immunosuppression);
9. Currently undergoing orthodontic treatment.

Primary outcomes:
measure: Change in the clinical attachment level at 180 days.
timeFrame: 180 days
Secondary outcomes:
measure: Changes in the fasting blood and glycated hemoglobin (HBA1C)
timeFrame: Baseline, 15, 30, 90 and 180 days
measure: Cytokines in the crevicular fluid
timeFrame: Baseline, 15, 30, 90 and 180 days
Other outcomes:
Locations:
city: São Paulo
country: Brazil
facility: Universidade Nove de Julho
state: SP
Study officials:
affiliation: University of Nove de Julho
name: Cristiane M Franca, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Evangelista EE, Franca CM, Veni P, de Oliveira Silva T, Goncalves RM, de Carvalho VF, Deana AM, Fernandes KP, Mesquita-Ferrari RA, Camacho CP, Bussadori SK, Alvarenga LH, Prates RA. Antimicrobial photodynamic therapy combined with periodontal treatment for metabolic control in patients with type 2 diabetes mellitus: study protocol for a randomized controlled trial. Trials. 2015 May 27;16:229. doi: 10.1186/s13063-015-0757-3.