Clinical trial NCT03622255: Evaluation of Enamel Matrix Derivative as an Adjunct to Minimally Invasive Non-surgical Treatment of Intrabony Defects.
Official title: Evaluation of Enamel Matrix Derivative as an Adjunct to Minimally Invasive Non-surgical Treatment of Intrabony Defects. A Randomized Controlled Clinical Trial.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Periodontal Diseases
Keywords: Intrabony defects
Minimally invasive non-surgical technique
Enamel Matrix Derivative
Lead sponsor: Aristotle University Of Thessaloniki
Sponsor class: OTHER
First posted: 2018-08-09
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: A software (www.randomizer.org) will be used by one of the investigators who will not participate in the clinical and radiographic measurements nor the therapeutic intervention, to generate a block randomization. Thus, participants will be randomized in one of the two groups in a way that there is no difference between the two groups regarding the initial depth of the intrabony defect. In patients with more than one intrabony defects meeting the inclusion criteria, a second randomization scheme with the same software will take place, to determine which will be included. The randomization results will be placed in sealed envelopes accessible only to the principal investigator and opened for each patient after the end of MINST to determine if EMD will be applied or not.
Primary purpose: TREATMENT

Brief summary: Aim:

The aim of this prospective, randomized, parallel arm, blind, controlled clinical trial is to compare the clinical and radiographic outcomes following regenerative treatment of intrabony periodontal defects using a Minimally Invasive Non-Surgical Technique (MINST) with or without the application of Enamel Matrix Derivative (EMD)

Research Hypothesis:

The hypothesis is that the adjunctive application of EMD will enhance the clinical and radiographic results of minimally invasive non- surgical treatment of intrabony defects. Radiographic bone fill will be the primary outcome of the research, whereas CAL gain and PD reduction will constitute the secondary outcomes.

Detailed description: Introduction Intrabony defects occur frequently in periodontitis and represent sites that, if left untreated, are at increased risk for disease progression. Although resective or repair procedures have been used to treat intrabony defects, aiming at their elimination, the treatment of choice is surgical periodontal regeneration. Over the last 30 years, histological and clinical studies have greatly improved our knowledge regarding regeneration of the periodontium and much attention has been given in clinical practice on the utilization of the principle of guided tissue regeneration (GTR), bone replacement grafts, biologics or their combination. Biologic factors appear attractive to alleviate local ⁄systemic factors counteracting periodontal wound healing ⁄ regeneration and untoward effects of biomaterials and devices as they become key components of novel regenerative technologies. The material most extensively researched as of today is enamel matrix derivative (EMD), which was first introduced in 1997.

Development of periodontal regeneration in the last 30 years has followed two distinctive, though totally different paths. The interest of researchers has so far focused on regenerative materials and products, on one side, and, on novel surgical approaches on the other side. In the area of materials and products, three different regenerative concepts have been mainly explored namely, barrier membranes, bone grafts, and wound healing modifiers, plus many combinations of the aforementioned. In the area of the surgical approaches, clinical innovation in flap design and handling as well as minimally invasive approaches has radically changed regenerative surgery.

In 1995, Harrel et al. introduced the first technical proposal of minimally invasive periodontal regenerative surgery (MIS) of isolated intrabony defects, with the aim to reduce surgical trauma, increase post-operative clot stability, improve flap adaptation and decrease time of surgery. Utilization of micro- surgical instruments and magnification was also proposed to minimize the trauma of the surgical procedure. The combination of this minimally invasive technique with EMD was also suggested by the same authors with successful long- term results.

Cortelini and Tonetti in 2007 presented a modification of the MIS technique. The authors proposed access of the defect- associated interdental papilla either with the modified papilla preservation technique- MPPT or the simplified papilla preservation technique- SPPT, depending on the width of the interdental space in combination with the application of EMD (MIST). Two years later, the same authors suggested a more tissue conservative technique, the modified- MIST (M-MIST). The surgical approach of M- MIST consists of a tiny intrasulcular incision performed only on the buccal side of the defect- associated tooth, which is connected with a horizontal incision performed as close as possible to the papilla tip. The palatal/lingual papilla are left untouched. In addition, Trombelli et al. suggested the single flap approach (SFA) in which a small incision is also performed only either buccally or palatially/lingually of the defect. Several randomized clinical trials published thereafter, comparing the efficacy of these minimally invasive techniques with or without the addition of regenerative factors, revealed equal results for both approaches, raising a series of hypotheses that focus more on the intrinsic healing potential of a wound when ideal conditions are provided with the surgical approach rather than the additive effect of regenerated material. Regenerative factors may increase the clot's initial stability and lead to better clinical results without though statistical significance.

More recently, a minimally invasive non- surgical technique (MINST) for treatment of intrabony defects was proposed. Initial clinical trials indicated comparable results to the surgical minimally invasive techniques in both clinical and microbiological outcomes. Considerable clinical and radiographic improvements after the application of MINST were also reported in a retrospective study, supporting its efficacy for treatment of intrabony defects. Additionally, an investigation designed to compare the effectiveness of EMD in combination with the MINST or MIST procedure in periodontal regeneration of deep intrabony defects concluded that the flapless procedure may be successfully applied in deep intrabony defects reaching clinical outcomes comparable with those of minimally invasive surgical approaches. So far, investigations comparing the outcomes of MINST as monotherapy or in combination with the use of EMD are missing. Thus, the purpose of this research is to compare the effectiveness of MINST with or without application of EMD in the treatment of intrabony defects.

Aim:

The aim of this prospective, randomized, parallel arm, blind, controlled clinical trial is to compare the clinical and radiographic outcomes following regenerative treatment of intrabony periodontal defects using a Minimally Invasive Non-Surgical Technique (MINST) with or without the application of Enamel Matrix Derivative (EMD)

Research Hypothesis:

The hypothesis is that the adjunctive application of EMD will enhance the clinical and radiographic results of minimally invasive non- surgical treatment of intrabony defects. Radiographic bone fill will be the primary outcome of the research, whereas CAL gain and PD reduction will constitute the secondary outcomes.

Procedure Before initiation of the study, the protocol will be approved by the Ethics Committee of the Dental School of the Aristotle University of Thessaloniki. In addition, informed consent will be signed by all participants.

Prior to inclusion in the study, an initial examination will be performed, including medical history, full- mouth plaque and bleeding scores, and PDs and CALs at 6 points on each tooth. In addition, oral hygiene instructions and motivation will be given. Patients will receive a supragingival debridement with ultrasonic instruments, in one session, without local anesthesia. Two weeks later a re-evaluation visit will be performed, including full- mouth plaque and bleeding scores and re-motivation to maintain proper oral hygiene. Four weeks after the initial visit (2 weeks after the first reassessment), the re- evaluation visit will be repeated. If the patient maintains appropriate oral hygiene levels (FMPS, FMBS \<20%) he/she will be included in the study. If the bleeding and plaque scores are \> 20%, a third re-evaluation visit will take place 2 weeks later (6 weeks after the initial visit) and if the scores reach the desired level, the patient will be included in the study. A software (www.randomizer.org) will be used by one of the investigators who will not participate in the clinical and radiographic measurements nor the therapeutic intervention, to generate a block randomization. Thus, participants will be randomized in one of the two groups in a way that there is no difference between the two groups regarding the initial depth of the intrabony defect. In patients with more than one intrabony defects meeting the inclusion criteria, a second randomization scheme with the same software will take place, to determine which will be included. The randomization results will be placed in sealed envelopes accessible only to the principal investigator and opened for each patient after the end of MINST to determine if EMD will be applied or not.

* Group A: application of minimally invasive non-surgical technique (MINST) for the intrabony defect and conventional non- surgical periodontal treatment in the rest of the quadrant teeth.
* Group B: application of minimally invasive non- surgical technique (MINST) with additional use of Enamel Matrix Derivative (EMD) for the intrabony defect and conventional non- surgical periodontal treatment in the rest of the quadrant teeth.

Treatment Procedures Group A: Minimally invasive non-surgical treatment (MINST). Root instrumentation under local anesthesia using specific hand instruments (micro- curettes) and piezon ultrasonic instruments in the area of intraosseous defect and scaling and root planing using conventional ultrasonic tips and hand instruments in the rest of the quadrant teeth.

Group B: Minimally invasive non-surgical treatment with application of enamel matrix derivative. Root instrumentation under local anesthesia using micro- curettes and piezon ultrasonic instruments in the area of intraosseous defect. Application of EDTA gel for 2 minutes on the root surface of the involved tooth. Rinsing with saline, drying and application of EMD to fill the defect. Scaling and root planing with conventional ultrasonic tips and hand instruments in the rest of the quadrant teeth.

Treatment in the remaining quadrants will proceed as following: the quadrant of the intrabony defect as well as the quadrant that will be in the same side of the mouth (either left or right) will be treated the same day with the MINST therapy. Both quadrants of the contralateral side will be treated in another day within the same week.

Treatment procedures will be performed with the use of 3.0 magnification and fiber optic lighting in both groups.

At the end of the treatment procedure, patients will be given instructions for use of a soft toothbrush without the additional use of interdental cleaning and use of 0.12% chlorhexidine solution (2 times a day) for 2 weeks. Two weeks after therapy, interdental cleaning will start with the adjunctive use of chlorhexidine gel 0.2% once a day for the first two weeks and 3 times a week for the rest of the study. Re-evaluation at 2 and 4 weeks, and 2, 3, 6, and 12 months will be scheduled. During these appointments FMPS and FMBS will be evaluated, oral hygiene instructions will be given and supragingival debridement will be performed when indicated. Clinical and radiographic measurements will be recorded at the 6th and 12th month examination.

Eligibility criteria: Inclusion Criteria:

* Be at least 18 years of age with a diagnosis of periodontitis.
* Have at least one isolated interproximal intrabony defect on a single-rooted tooth or a mandibular molar not extending to the furcation area with radiographic depth ranging between 3 mm-7 mm, pocket depth and clinical attachment loss ≥6 mm and radiographic defect angle ≤ 35o
* Proper oral hygiene: full-mouth plaque score (FMPS) ≤20% και full-mouth bleeding score (FMBS) ≤20%
* Systemically healthy (absence of systemic conditions that can affect the treatment outcome of periodontal therapy)

Exclusion Criteria:

* Pregnant or lactating female
* Current acute infection
* Non- surgical periodontal treatment the last 6 months or surgical periodontal treatment the last 12 months
* Teeth having an improper endodontic therapy with clinical signs of infection or subgingival restorations
* Tooth mobility 2nd- 3rd degree
* History of radiation therapy in the head and neck region

Primary outcomes:
measure: Radiographic bone fill
timeFrame: Change from baseline to 12 months
Secondary outcomes:
measure: Clinical attachment gain
timeFrame: Change from baseline to 12 months
measure: Pocket depth reduction
timeFrame: Change from baseline to 12 months
Other outcomes:
measure: Recession
timeFrame: Change from baseline to 12 months
measure: Full mouth plaque score
timeFrame: Change from baseline to 12 months
measure: Full mouth bleeding score
timeFrame: Change from baseline to 12 months
measure: Distance from the CEJ or the margin of a restoration to the bottom of the defect (CEJ-BD)
timeFrame: Change from baseline to 12 months
measure: Distance from the Cementoenamel Junction to the bone crest (CEJ-BC)
timeFrame: Change from baseline to 12 months
measure: Depth of the intraosseous defect
timeFrame: Change from baseline to 12 months
measure: Angle of the intraosseous defect
timeFrame: Change from baseline to 12 months
Locations:
city: Thessaloníki
country: Greece
facility: Aristotle University of Thessaloniki, School of Dentistry
state: Thessaloniki
Study officials:
affiliation: Aristotle University Of Thessaloniki
name: Ioannis Vouros, DDS, Ph.D
role: PRINCIPAL_INVESTIGATOR
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