Flapless Application of Enamel Matrix Derivative in Class II Mandibular Furcation Defects

Periodontal Diseases Clinical Trial

Official title:

Flapless Application of Enamel Matrix Derivative in Class II Mandibular Furcation Defects: a Randomized Clinical Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05541614
• Other study ID #: 155/14-03-2022
• Status: Recruiting
• Phase: N/A
• Start date: October 15, 2022
• Est. completion date: April 15, 2025

Study information

• Verified date: March 2023
• Source: Aristotle University Of Thessaloniki
• Contact: Georgios S Chatzopoulos, DDS, MS
• Phone: +30 6970836897
• Email: gschatzopoulos[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Patients diagnosed with stage III or IV periodontitis that exhibit mandibular first or second molars with increased periodontal probing depth (PPD > 4 mm) and class II buccal mandibular furcation defects (horizontal probing depth of >= 3 mm ) will be recruited. This study will be a non-inferiority, prospective, randomized, double-blind controlled clinical trial with a parallel design. Patient will be recruited from the clinics of the School of Dentistry at the Aristotle University of Thessaloniki and private dental practices in Thessaloniki, Greece. Initially, non-surgical periodontal treatment will be performed through scaling and root planning in combination with oral hygiene instructions and motivation. The re-evaluation will be performed 4-6 weeks following the treatment and the patients who meet the inclusion criteria will be included in the study. Patients will be randomly allocated at a 1:1 ratio to either subgingival debridement and flapless application of EMD (test group) into the affected furcation defect or to periodontal surgery in combination with EMD application (control group). Periodontal and radiographic parameters, patient reported outcomes, oral cavity measurements and gingival crevicular fluid will be collected before as well as up to 9 months following the treatment.

Description:

The first step in periodontal therapy aims to successfully remove supragingival dental biofilm, improve oral hygiene and control potential risk factors. During the second step of treatment, the "cause-related therapy", non-surgical periodontal treatment consisting of subgingival debridement aiming to reduce plaque accumulation, calculus deposits, gingival inflammation, pocket depths is performed,which is effective for gaining attachment level. However, non-surgical periodontal treatment per se rarely translates into periodontal regeneration. In patients with severe periodontal disease residual periodontal pockets may remain after an initial therapy. Furcation defects often do not respond favourably to non-surgical periodontal therapy and are associated with elevated risk of progression. The elimination of these residual periodontal pockets can be achieved at the thirdstep of the treatment by resective or regenerative procedures based on the morphology of the defect or alternatively repeated subgingival instrumentation with or without adjunctive therapies can be carried out. Regeneration of the periodontal tissues includes cementum, periodontal ligament (PDL) and alveolar bone. Currently, several flap designs and biomaterials have been utilized and tested in the literature aiming at periodontal regeneration including bone grafts, bone substitute materials, growth factors, enamel matrix derivative proteins (EMD), guided tissue regeneration or even a combination of these materials. Although the application of EMD in conjunction with non-surgical periodontal treatment has shown a positive effect with evidence of regeneration, its effectiveness remains inconclusive.

Further studies in various disease conditions (intrabony defects, furcation defects, suprabony defects) are needed to confirm the potential benefit of adjunctive EMD application in combination with subgingival debridement (non surgical periodontal therapy). No study to our knowledge has tested the efficacy of flapless application of EMD in the healing of molars with furcation involvement.

Study design: Non-inferiority, double-blind, randomized, controlled clinical trial with parallel design.

Null Hypothesis: The adjunctive flapless use of enamel matrix derivative (EMD) during subgingival debridement in patients diagnosed with Stage III or IV periodontitis that exhibit class II buccal mandibular furcation involvement leads to inferior outcomes in clinical and radiographic as well as in biomarkers in comparison with surgical periodontal treatment with EMD.

Hypothesis: The adjunctive flapless use of enamel matrix derivative (EMD) during subgingival debridement in patients diagnosed with Stage III or IV periodontitis that exhibit class II buccal mandibular furcation involvement results in noninferior/equivalent outcome in clinical and radiographic variables as well as in biomarkers in comparison with surgical periodontal treatment with EMD.

Aim: The aim of this study is to investigate the non-inferiority of the flapless application of enamel matrix derivate (EMD) in addition to subgingival debridement in class II buccal mandibular furcationsin regards to the clinical and radiographic outcome as well as the level of biomarkers related to periodontal disease activity, inflammation and regeneration compared with periodontal surgery with EMD.

Methods: Patients diagnosed with stage III or IV periodontitis that exhibit mandibular first or second molars with increased periodontal probing depth (PPD > 4 mm) and class II buccal mandibular furcation defects (horizontal probing depth of >= 3 mm)will be recruited. This study will be a non-inferiority, prospective, randomized, double-blind controlled clinical trial with a parallel design.

Patient will be recruited from the clinics of the School of Dentistry at the Aristotle University of Thessaloniki and private dental practices in Thessaloniki, Greece.

Pre-treatment: Non-surgical periodontal treatment will be performed through scaling and root planning in combination with oral hygiene instructions and motivation. The reevaluation will be performed 4-6 weeks following the treatment and the patients who meet the inclusion criteria will be included in the study. Patients will be randomly allocated at a 1:1 ratio to either subgingival debridement and flapless application of EMD (test group) into the affected furcation defect or to periodontal surgery in combination with EMD application (control group). Periodontal and radiographic parameters, patient reported outcomes, oral cavity measurements and gingival crevicular fluid will be collected before as well as up to 9 months following the treatment.

Sample size calculation An estimate of the expected PPD reduction from OFD+EDTA+EMD was drawn from Casarin et al. 2010. The mean PPD reduction following OFD+EDTA+EMD was 1.9 +/- 1.6 mm and 1.0 +/-1.3 mm when OFD+EDTA was only performed. The differential effect of using EMD in a surgical periodontal treatment amounts about 1 mm. The sample size calculation was performed using α=0.05 and 90% power to detect a difference of 1 mm between treatment groups (MINST+Flapless EMD vs MIST+EMD) which is clinically significant and detectable. The estimated standard deviation was 1 mm. The required sample size was calculated to be 18 individuals in each group (total 36). Considering that some patients might be lost during the follow-up, a total of 44 participants will be enrolled (dropout rate of 20%). When the power was set to 80%, the required sample size is 13 patients per group (total 26). Considering a dropout rate of 20%, a total of 32 patients will be enrolled.

Statistical methods Descriptive statistics will be used to present the results of the sample's characteristics (mean and standard deviation for age, number of teeth, clinical periodontal and radiographic parameters; counts and percentages for categorical variables such as gender, medical and smoking history etc). The distribution of the sample will be measured with the Shapiro-Wilk test. In case of normal distribution: paired and unpaired t-tests will be utilized. In case a non-parametric test is used, Wilcoxon signed-rank and Mann Whitney U tests will be utilized. Chi-square test will be also used to compare categorical variables. GCF and periodontal measurements can be correlated with Spearman or Pearson rank correlation test. A statistical significant result will be set to a threshold level of <=0.05.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 44
• Est. completion date: April 15, 2025
• Est. primary completion date: April 15, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Individuals of at least 18 years of age with a diagnosis of stage III or IV periodontitis.

• Have at least one class II furcation defect with PPD >4 mm and horizontal probing depth of >= 3 mm in a mandibular first or second molar.

• Teeth have to be vital or properly treated endodontically.

• Gingival recession = 2mm on furcation site

• Proper oral hygiene: full-mouth plaque score (FMPS) =20%.

• Systemically healthy (absence of systemic conditions such as diabetes mellitus that can affect the treatment outcome of periodontal therapy)

• Ability to understand the study procedures and comply with them through the length of the study.

• Given written informed consent form for participation in the study.

Exclusion Criteria:

• Pregnant or lactating female (self-reported).

• Current acute infection.

• Non-surgical periodontal treatment within the last 6 months or/and surgical periodontal treatment the last 12 months before the initial pre-treatment.

• Need for antibiotic premedication.

• Antibiotic treatment in the previous 3 months.

• Allergy to any materials or medications that could be used during or after the procedure.

• Teeth having an improper endodontic therapy with clinical signs of infection or subgingival restorations.

• Tooth mobility of 2nd and 3rd degree.

• History of radiation therapy in the head and neck region.

• Chronic use of medications that may alter the response of periodontal tissues.

• Smoke = 10 cigarettes/day.

Related Conditions & MeSH terms

• Furcation Defects
• Periodontal Diseases

Intervention

Other:
• Emdogain® FL (flapless Emdogain®) - Enamel Matrix Derivative
Emdogain® FL has been shown to enhance the early healing of periodontal soft tissue wounds resulting from the instrumentation of periodontal pockets.
• Emdogain® - Enamel Matrix Derivative
Enamel matrix derivative (EMD) has been widely used in the surgical treatment of periodontal disease and in furcation defects.

Locations

Country	Name	City	State
Greece	Aristotle University of Thessaloniki, School of Dentistry	Thessaloníki	Thessaloniki

Sponsors (1)

Lead Sponsor	Collaborator
Aristotle University Of Thessaloniki

Country where clinical trial is conducted

Greece, 

References & Publications (1)

- Graziani F, Karapetsa D, Mardas N, Leow N, Donos N (2018) Surgical treatment of the residual periodontal pocket. Periodontol 2000 76:150-163. - Lang NP, Salvi GE, Sculean A (2019) Nonsurgical therapy for teeth and implants-When and why? Periodontol 200079(1):15-21. doi: 10.1111/prd.12240. - Kaldahl WB, Kalkwarf KL, Patil KD, Molvar MP. Responses of four tooth and site groupings to periodontal therapy. J Periodontol. 1990 Mar;61(3):173-9. doi: 10.1902/jop.1990.61.3.173. PMID: 2181110. - Tomasi C, Leyland AH, Wennström JL. Factors influencing the outcome of non-surgical periodontal treatment: a multilevel approach. J Clin Periodontol. 2007 Aug;34(8):682-90. doi: 10.1111/j.1600-051X.2007.01111.x. PMID: 17635246. - Wang HL, Burgett FG, Shyr Y, Ramfjord S. The influence of molar furcation involvement and mobility on future clinical periodontal attachment loss. J Periodontol. 1994 Jan;65(1):25-9. doi: 10.1902/jop.1994.65.1.25. PMID: 8133412. - Nibali L, Zavattini A, Nagata K, Di Iorio A, Lin GH, Needleman I, Donos N. Tooth loss in molars with and without furcation involvement - a systematic review and meta-analysis. J Clin Periodontol. 2016 Feb;43(2):156-66. doi: 10.1111/jcpe.12497. Epub 2016 Feb 12. PMID: 26932323. - Meza Mauricio J, Furquim CP, Bustillos-Torrez W, Soto-Peñaloza D, Peñarrocha-Oltra D, Retamal- Valdes B, Faveri M (2021) Does enamel matrix derivative application provide additional clinical benefits in the treatment of maxillary Miller class I and II gingival recession? A systematic review and meta-analysis. Clin Oral Investig25(4):1613-1626. doi: 10.1007/s00784-021-03782-2. - Graziani F, Gennai S, Cei S, Ducci F, Discepoli N, Carmignani A, Tonetti M (2014) Does enamel matrix derivative application provide additional clinical benefits in residual periodontal pockets associated with suprabony defects? A systematic review and meta-analysis of randomized clinical trials. J Clin Periodontol;41(4):377-86. doi: 10.1111/jcpe.12218. - Stavropoulos A, Bertl K, Spineli LM, Sculean A, Cortellini P, Tonetti M (2021) Medium- and longterm clinical benefits of periodontal regenerative/reconstructive procedures in intrabony defects: Systematic review and network meta-analysis of randomized controlled clinical studies. J Clin Periodontol48(3):410-430. doi: 10.1111/jcpe.13409. - Esberg A, Isehed C, Holmlund A, Lundberg P (2019) Peri-implant crevicular fluid proteome before and after adjunctive enamel matrix derivative treatment of peri-implantitis. J Clin Periodontol46(6):669-677. doi: 10.1111/jcpe.13108. - Oliveira HFE, Verri F, Lemos CA, Cruz R, Batista VES, Pellizzer E, Santinoni C (2020) Clinical Evidence for Treatment of Class II Periodontal Furcation Defects. Systematic Review and Metaanalysis. J Int Acad Periodontol22(3):117-128. - Wennstrom JL, Lindhe J (2002) Some effects of enamel matrix proteins on wound healing in the dentogingival region. J Clin Periodontol29:9-14. - Mark R, Mohan R, Gundappa M, Balaji MDS, Vijay VK, Umayal M. Comparative Evaluation of Periodontal Osseous Defects Using Direct Digital Radiography and Cone-Beam Computed Tomography. J Pharm Bioallied Sci. 2021 Jun;13(Suppl 1):S306-S311. doi: 10.4103/jpbs.JPBS_804_20. Epub 2021 Jun 5. PMID: 34447099; PMCID: PMC8375921. - Assiri H, Dawasaz AA, Alahmari A, Asiri Z. Cone beam computed tomography (CBCT) in periodontal diseases: a Systematic review based on the efficacy model. BMC Oral Health. 2020 Jul 8;20(1):191. doi: 10.1186/s12903- 020-01106-6. PMID: 32641102; PMCID: PMC7341656. - Walter C, Schmidt JC, Rinne CA, Mendes S, Dula K, Sculean A. Cone beam computed tomography (CBCT) for diagnosis and treatment planning in periodontology: systematic review update. Clin Oral Investig. 2020 Sep;24(9):2943-2958. doi: 10.1007/s00784-020-03326-0. Epub 2020 Jul 3. PMID: 32617781. - Yusof NAM, Noor E, Reduwan NH, Yusof MYPM. Diagnostic accuracy of periapical radiograph, cone beam computed tomography, and intrasurgical linear measurement techniques for assessing furcation defects: a longitudinal randomised controlled trial. Clin Oral Investig. 2021 Mar;25(3):923-932. doi: 10.1007/s00784-020- 03380-8. Epub 2020 Jun 14. PMID: 32535703. - Zhang W, Foss K, Wang BY. A retrospective study on molar furcation assessment via clinical detection, intraoral radiography and cone beam computed tomography. BMC Oral Health. 2018 May 3;18(1):75. doi: 10.1186/s12903- 018-0544-0. PMID: 29724208; PMCID: PMC5934848.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Periodontal probing pocket depth (PPD) change	Changes in pocket probing depth will be measured using a periodontal probe. The depth of the sulcus will be assessed by gently inserting a graduated periodontal probe until resistance is encountered at the base of the sulcus. The depth from the free gingival margin to the base of the sulcus is measured in millimeters and represents PPD.	9 months after treatment
Secondary	Horizontal and vertical furcation involvement change.	Changes in horizontal and vertical furcation involvement will be measured using a periodontal probe.	9 months after treatment
Secondary	Periodontal clinical attachment level (CAL) change.	Changes in clinical attachment level will be measured using a periodontal probe.	9 months after treatment
Secondary	Bleeding on Probing (BOP) change	Bleeding on Probing will be tested using a periodontal probe that is carefully introduced to the bottom of the pocket gently.	9 months after treatment
Secondary	Gingival recession (REC) change	Changes in gingival recession will be measured using a periodontal probe.	9 months after treatment
Secondary	Furcation involvement grade change	Proportion of sites demonstrating change in furcation grade level as measured with Nabers probe	9 months after treatment
Secondary	Radiographic defect depth, height, root trunk and width.	Assessment of the defect depth, height, root trunk and width using Cone-beam computed tomography systems (CBCT) and periapical radiographs and subtraction radiography	9 months after treatment
Secondary	Levels of markers related to periodontal disease activity, inflammation as well as regeneration in the GCF.	The levels of markers will be assessed using gingival crevicular fluid (GCF) and analyzed with multiplex assays (in pg or ng based on the assays)	9 months after treatment
Secondary	Patient-reported outcome measures	Patient-reported outcome measures using Visual Analogue Scales (VAS) Visual analogue Scale: range from 0 mm "no", to 100 mm," the worst possible"	9 months after treatment
Secondary	Oral health-related quality of life	Oral health-related quality of life measures using OHIP-14 (Greek version) The OHIP-14 captures seven domains of OHRQoL with two items per domain: functional limitation, physical pain, psychological discomfort, physical disability, psychological disability, social disability, and handicap.; The responses are rated on a 5-point Likert scale: 0 = never; 1 = hardly ever; 2 = occasionally; 3 = fairly often; 4 = very often/every day. The OHIP-14 scores can range from 0 to 56 and are calculated by summing the ordinal values for the 14 items.	9 months after treatment