Antimicrobial Photodynamic Therapy Mediated by PapaMBlue® on Chronic Periodontal Disease

Antimicrobial Photodynamic Therapy Mediated by PapaMBlue® on Chronic Periodontal Disease - Randomized Blind Controlled Trial

The elimination of the pathogenic microorganisms of the periodontal pocket is one of the main points for success in periodontal treatment. The objective of this study is to investigate the clinical and antimicrobial effect of papain-mediated photodynamic therapy in the clinical treatment of periodontal disease. Twenty patients with chronic periodontitis will be selected. Patients will be divided randomly into two groups (n = 10), and the control group will receive conventional periodontal treatment and group II will receive conventional treatment and antimicrobial photodynamic therapy (aPDT). Conventional treatment will consist of oral hygiene guidance, with brushing technique instructions and recommendation of daily flossing. The calculus deposits on the teeth will be removed with ultrasound equipment and curettes for scraping and root planing. The aPDT will be performed at the end of each periodontal treatment session, at sites with bags greater than or equal to 4 mm. The PapaMblue® photosensitizer will be deposited in the periodontal pockets with a syringe and a pre-irradiation time of 1 min will be adopted. Then, the laser emitting wavelength of 660 nm, with power of 100 mW, for 2 min, radiant exposure of 30 J/cm2 and power density of 250 mW/cm2 will be applied. Patients will undergo clinical evaluations before treatment (day 1) and 30, 60 and 90 days after the end of treatment. Microbiological evaluations will be made before and 30 days after treatment. The distribution of the data within each group and the homogeneity of the variances will be verified. With this information, the most appropriate statistical test for each evaluation will be used. The sample calculation is based on the literature and the significance level of 5% will be adopted.

Study Overview

• Status: Unknown
• Conditions: Periodontal Diseases
• Intervention / Treatment: Procedure: Conventional treatment; Radiation: aPDT

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• The patient must have chronic periodontitis (AAP, 2001);
• At least 10 present teeth, with at least 3 sites with clinical depth of probing greater than 4 mm;
• The patient must be in periodontal treatment at the Dental Clinic of Universidade Nove de Julho, institution where this research will be carried out;

Exclusion Criteria:

• Smokers or former smokers who discontinued the habit less than 12 months prior to selection;
• Uncontrolled diabetes;
• Anemia;
• Cancer;
• Pregnant women;
• Use of antibiotics in the last 6 months;
• Use of anti-inflammatory in the last 3 months;
• Coagulation disorder (use of anti-coagulant, presence of liver diseases, thrombocytopenia and immunosuppression);
• Patients under orthodontic treatment;
• Patients who maintain a biofilm index greater than 25%.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Control group; In this group, the participants will be submitted to the conventional treatment. The treatment will consist of oral hygiene orientation, with instructions of brushing technique and recommendation of the daily use of dental floss. All patients will receive a demonstration of oral hygiene techniques. The calculus deposits on the teeth will be removed with ultrasound equipment and curettes for root scaling and straightening. After the use of ultrasound and curettes, bicarbonate jet will be used to remove dental biofilm. Treatment will be performed in 2 to 4 sessions under local anesthesia (typically 2% mepivacaine with 1: 100,000 noradrenaline). Gracey periodontal curettes (numbers 3/4, 7/8, 11/12 and 13/14) and Mc Call curettes for removal of the dental calculus will be used. Other biofilm-retaining factors, such as carious lesions, condemned teeth, and ill-adapted restorations, will be removed during these periodontal treatment sessions.	Procedure: Conventional treatment; The treatment will consist of oral hygiene orientation, with instructions of brushing technique and recommendation of the daily use of dental floss. All patients will receive a demonstration of oral hygiene techniques. The calculus deposits on the teeth will be removed with ultrasound equipment and curettes for root scaling and straightening. After the use of ultrasound and curettes, bicarbonate jet will be used to remove dental biofilm. Treatment will be performed in 2 to 4 sessions under local anesthesia (typically 2% mepivacaine with 1: 100,000 noradrenaline). Gracey periodontal curettes (numbers 3/4, 7/8, 11/12 and 13/14) and Mc Call curettes for removal of the dental calculus will be used. Other biofilm-retaining factors, such as carious lesions, condemned teeth, and ill-adapted restorations, will be removed during these periodontal treatment sessions.
Experimental: aPDT group; In this group, besides the conventional treatments, patients will also receive aPDT. aPDT will be performed at the end of each periodontal treatment session, at sites with bags greater than or equal to 4 mm. The photosensitizer PapaMBlue® (F & A Ltda, São Paulo, Brazil) will be deposited in the pouches with a syringe, with the application in coronal direction, and a time of 1 min of pre-irradiation will be adopted so that the substance can stain bacterial biofilm (according to the manufacturer's information). Next, the diode laser emitting wavelength of ʎ=660 nm, with power of P=100 mW, will be applied. The laser will be applied to the mucosa, over the oral epithelium with an optical fiber. Irradiation will be performed until the entire periodontal pocket is illuminated for 2 min at each point. Each irradiation point will be approximately 0.4cm2, which will result in energy density of 30 J/cm2 in 2 min irradiation. The irradiation will have a constant power density of 250 mW/cm2.	Procedure: Conventional treatment; The treatment will consist of oral hygiene orientation, with instructions of brushing technique and recommendation of the daily use of dental floss. All patients will receive a demonstration of oral hygiene techniques. The calculus deposits on the teeth will be removed with ultrasound equipment and curettes for root scaling and straightening. After the use of ultrasound and curettes, bicarbonate jet will be used to remove dental biofilm. Treatment will be performed in 2 to 4 sessions under local anesthesia (typically 2% mepivacaine with 1: 100,000 noradrenaline). Gracey periodontal curettes (numbers 3/4, 7/8, 11/12 and 13/14) and Mc Call curettes for removal of the dental calculus will be used. Other biofilm-retaining factors, such as carious lesions, condemned teeth, and ill-adapted restorations, will be removed during these periodontal treatment sessions.; Radiation: aPDT; aPDT will be performed at the end of each periodontal treatment session, at sites with bags greater than or equal to 4 mm. The photosensitizer PapaMBlue® (F & A Ltda, São Paulo, Brazil) will be deposited in the pouches with a syringe, with the application in coronal direction, and a time of 1 min of pre-irradiation will be adopted so that the substance can stain bacterial biofilm (according to the manufacturer's information). Next, the diode laser emitting wavelength of ʎ=660 nm, with power of P=100 mW, will be applied. The laser will be applied to the mucosa, over the oral epithelium with an optical fiber. Irradiation will be performed until the entire periodontal pocket is illuminated for 2 min at each point. Each irradiation point will be approximately 0.4cm2, which will result in energy density of 30 J/cm2 in 2 min irradiation. The irradiation will have a constant power density of 250 mW/cm2.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in probing depth	For the evaluation of probing depth, a single trained, calibrated examiner will examine 6 sites of each tooth with a 15mm North Carolina millimeter probe (Hu-Friedy, Chicago, IL, USA) for the measurement of probing depth in milimeters. The evaluation will be performed at the beginning of treatment, 30, 60 and 90 days after the tretaments.	Baseline, 30, 60 and 90 days after treatment.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in probing bleeding	For the evaluation of bleeding, a single trained, calibrated examiner will examine 6 sites of each tooth using a 15mm North Carolina millimeter probe (Hu-Friedy, Chicago, IL, USA) to check whether there is bleeding during the probing. The evaluation will be performed at the beginning of treatment, 30, 60 and 90 days after the treatments.	Baseline, 30, 60 and 90 days after treatment.
Change in loss of clinical insertion	A single trained, calibrated examiner will examine 6 sites in each tooth with a 15mm North Carolina millimeter probe (Hu-Friedy, Chicago, IL, USA) for the measurement of loss of clinical insertion in milimeters. The evaluation will be performed at the beginning of treatment, 30, 60 and 90 days after the treatments.	Baseline, 30, 60 and 90 days after treatment.
Change in plaque index	For the evaluation of plaque index, a single trained, calibrated examiner will examine 6 sites of each tooth with a 15mm North Carolina millimeter probe (Hu-Friedy, Chicago, IL, USA) for the measurement of the amount of plaque in milimeters. The evaluation will be performed at the beginning of treatment, 30, 60 and 90 days after treatment.	Baseline, 30, 60 and 90 days after treatment.
Microbiological examination (change in CFUs (Colony Forming Units))	The microbiological examination will be performed from subgingival biofilm samples collected from the periodontal pockets. Two collections will be performed at each experimental site before and immediately after treatments. For the collection of the subgingival biofilm, a relative isolation of the teeth with cotton rollers will be performed, the supra-gingival biofilm will be removed with sterile gauze, and the subgingival biofilm sample will be obtained by inserting a sterile absorbent paper tip (no. 30) into the inside of the pocket, being held in place for 30s. The tips will be removed and stored in properly identified sterile plastic microtubes, with each paper cone being stored in a different microtube. The samples will be used to determine the CFUs (Colony Forming Units).	Baseline, 30, 60 and 90 days after treatment.

Collaborators and Investigators

• Sponsor: University of Nove de Julho

Study record dates

Study Major Dates

• Study Start (Anticipated): March 15, 2019
• Primary Completion (Anticipated): November 15, 2019
• Study Completion (Anticipated): April 15, 2020

Study Registration Dates

• First Submitted: February 22, 2019
• First Submitted That Met QC Criteria: February 25, 2019
• First Posted (Actual): February 26, 2019

Study Record Updates

• Last Update Posted (Actual): February 26, 2019
• Last Update Submitted That Met QC Criteria: February 25, 2019
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Stomatognathic Diseases; Mouth Diseases; Periodontitis; Periodontal Diseases; Chronic Periodontitis
• Other Study ID Numbers: GIU

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No