Periodontal DiseasesNCT05541614
Flapless Application of Enamel Matrix Derivative in Class II Mandibular Furcation Defects
A study testing Emdogain® FL (flapless Emdogain®) - Enamel Matrix Derivative and Emdogain® - Enamel Matrix Derivative in people with Periodontal Diseases and Periodontal Disease, AVDC Stage 3, run by Aristotle University Of Thessaloniki at 1 site in Greece.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Periodontal Diseases, Periodontal Disease, AVDC Stage 3, Periodontal Disease, AVDC Stage 4
- What is being tested?
- Emdogain® FL (flapless Emdogain®) - Enamel Matrix Derivative and Emdogain® - Enamel Matrix Derivative
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 44 participants
- Where
- 1 siteGreece
- Study dates
- 15 Oct 2022to 15 Apr 2025
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 11Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
Greece1 site, 1 recruiting
- Recruiting
Aristotle University of Thessaloniki, School of Dentistry
Thessaloniki, Thessaloniki
Georgios Chatzopoulos, DDS, MS
About this study
Official title: Flapless Application of Enamel Matrix Derivative in Class II Mandibular Furcation Defects: a Randomized Clinical Trial
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.
Read the detailed 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.
- Conditions
- Periodontal Diseases, Periodontal Disease, AVDC Stage 3, Periodontal Disease, AVDC Stage 4, Furcation Defects
- Being tested
- Emdogain® FL (flapless Emdogain®) - Enamel Matrix Derivative, Emdogain® - Enamel Matrix Derivative
- Keywords
- Periodontal disease, Enamel Matrix Derivative, EMD, Flapless, MINST, Periodontal treatment, Furcation defect
- Medical subject headings
- Periodontal Diseases, Furcation Defects
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Emdogain® FL (flapless Emdogain®) - Enamel Matrix DerivativeOther
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 DerivativeOther
Enamel matrix derivative (EMD) has been widely used in the surgical treatment of periodontal disease and in furcation defects.
| Study group | Role | What they receive |
|---|---|---|
| Subgingival debridement + Flapless Enamel Matrix Derivative | Experimental | Subgingival debridement following a minimally-invasive non-surgical treatment (MINST) approach with flapless application of EMD
Root instrumentation under local anesthesia using mini hand instruments (mini curettes) and ultrasonic instruments with fine tips in the furcation area of mandibular first or second molars with class II buccal furcation defects. EDTA gel will be applied for 2 minutes on the affected root surfaces, followed by rinsing with saline and drying prior to the application of Emdogain® FL. Emdogain® FL has been shown to enhance the early healing of periodontal soft tissue wounds resulting from the instrumentation of periodontal pockets. Receives: Other: Emdogain® FL (flapless Emdogain®) - Enamel Matrix Derivative |
| Periodontal surgery + Enamel Matrix Derivative | Active comparator | Periodontal surgery following a minimally-invasive surgical treatment (MIST) protocol with application of EMD
Following local anesthesia, minimal flap elevation on the buccal aspect of first or second molars associated with a grade II furcation defect will be performed.Removal of granulation tissues and root instrumentation with mini hand instruments (mini curettes) and ultrasonic instruments with fine tips in the furcation area will then be carried out. EDTA gel will be applied for 2 minutes on the affected root surfaces, followed by rinsing with saline and drying prior to the application of Emdogain®. Then, the surgical flaps will be positioned and sutured in order to completely cover the defects. Receives: Other: Emdogain® - Enamel Matrix Derivative |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 9 months after treatment
Secondary outcomes (9)
Horizontal and vertical furcation involvement change.
Changes in horizontal and vertical furcation involvement will be measured using a periodontal probe.
Measured: 9 months after treatment
Periodontal clinical attachment level (CAL) change.
Changes in clinical attachment level will be measured using a periodontal probe.
Measured: 9 months after treatment
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.
Measured: 9 months after treatment
Gingival recession (REC) change
Changes in gingival recession will be measured using a periodontal probe.
Measured: 9 months after treatment
Furcation involvement grade change
Proportion of sites demonstrating change in furcation grade level as measured with Nabers probe
Measured: 9 months after treatment
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
Measured: 9 months after treatment
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)
Measured: 9 months after treatment
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"
Measured: 9 months after treatment
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.
Measured: 9 months after treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Sep 2022
- Study start15 Oct 2022
- Primary completion15 Apr 2025 (estimated)
- Study completion15 Apr 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Periodontal DiseasesStudies of the same condition, open and under way.
- More trials run by Aristotle University Of ThessalonikiThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 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). The selected sites will be randomly assigned to test and control groups using an online software for randomization. The therapist will be kept unaware of treatment allocation until the treatment.
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 44 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Aristotle University Of Thessaloniki
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Georgios Chatzopoulos, Aristotle University Of Thessaloniki
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05541614
- Sponsor's protocol ID
- 155/14-03-2022
- Status last verified
- Mar 2023
- First submitted
- 13 Sep 2022
- Last updated
- 7 Mar 2023
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
- 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.
Chatzopoulos GS, Kaklamanos EG, Vouros I, Mikrogeorgis G, Doufexi AE, Tsalikis L. Clinical, Radiographic and Patient-Centred Outcomes of MINST Versus MIST With Enamel Matrix Derivative in Class II Mandibular Furcation Defects: A Randomised Controlled Trial. J Clin Periodontol. 2026 Jul 11. doi: 10.1111/jcpe.70167. Online ahead of print.
PubMed 42433105
Study at a glance
From the registry record, last updated by the sponsor on 7 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Flapless Application of Enamel Matrix Derivative in Class II Mandibular Furcation Defects: a Randomized Clinical Trial
- ClinicalTrials.gov ID
- NCT05541614
- Acronym / sponsor ID
- 155/14-03-2022
- Conditions
- Periodontal Diseases, Periodontal Disease, AVDC Stage 3, Periodontal Disease, AVDC Stage 4, Furcation Defects
- Keywords
- Periodontal disease, Enamel Matrix Derivative, EMD, Flapless, MINST, Periodontal treatment, Furcation defect
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 44 participants (estimated)
- Lead sponsor
- Aristotle University Of ThessalonikiUniversity, hospital or other
- Study start
- 15 Oct 2022 (actual)
- Primary completion
- 15 Apr 2025 (estimated)
- Study completion
- 15 Apr 2025 (estimated)
- First posted
- 15 Sep 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
- Model description
- 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). The selected sites will be randomly assigned to test and control groups using an online software for randomization. The therapist will be kept unaware of treatment allocation until the treatment.
| Arm | Type | Receives |
|---|---|---|
| Subgingival debridement + Flapless Enamel Matrix Derivative | Experimental | Other: Emdogain® FL (flapless Emdogain®) - Enamel Matrix DerivativeSubgingival debridement following a minimally-invasive non-surgical treatment (MINST) approach with flapless application of EMD Root instrumentation under local anesthesia using mini hand instruments (mini curettes) and ultrasonic instruments with fine tips in the furcation area of mandibular first or second molars with class II buccal furcation defects. EDTA gel will be applied for 2 minutes on the affected root surfaces, followed by rinsing with saline and drying prior to the application of Emdogain® FL. Emdogain® FL has been shown to enhance the early healing of periodontal soft tissue wounds resulting from the instrumentation of periodontal pockets. |
| Periodontal surgery + Enamel Matrix Derivative | Active comparator | Other: Emdogain® - Enamel Matrix DerivativePeriodontal surgery following a minimally-invasive surgical treatment (MIST) protocol with application of EMD Following local anesthesia, minimal flap elevation on the buccal aspect of first or second molars associated with a grade II furcation defect will be performed.Removal of granulation tissues and root instrumentation with mini hand instruments (mini curettes) and ultrasonic instruments with fine tips in the furcation area will then be carried out. EDTA gel will be applied for 2 minutes on the affected root surfaces, followed by rinsing with saline and drying prior to the application of Emdogain®. Then, the surgical flaps will be positioned and sutured in order to completely cover the defects. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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%.
Key exclusion criteria (11 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Emdogain® FL (flapless Emdogain®) - Enamel Matrix DerivativeEmdogain® FL has been shown to enhance the early healing of periodontal soft tissue wounds resulting from the instrumentation of periodontal pockets. | Other | Subgingival debridement + Flapless Enamel Matrix Derivative |
| Emdogain® - Enamel Matrix DerivativeEnamel matrix derivative (EMD) has been widely used in the surgical treatment of periodontal disease and in furcation defects. | Other | Periodontal surgery + Enamel Matrix Derivative |
Primary outcome
Periodontal probing pocket depth (PPD) change
Time frame: 9 months after treatment
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 secondary outcomes
Horizontal and vertical furcation involvement change.
Time frame: 9 months after treatment
Periodontal clinical attachment level (CAL) change.
Time frame: 9 months after treatment
Bleeding on Probing (BOP) change
Time frame: 9 months after treatment
Gingival recession (REC) change
Time frame: 9 months after treatment
Furcation involvement grade change
Time frame: 9 months after treatment
Radiographic defect depth, height, root trunk and width.
Time frame: 9 months after treatment
Levels of markers related to periodontal disease activity, inflammation as well as regeneration in the GCF.
Time frame: 9 months after treatment
Patient-reported outcome measures
Time frame: 9 months after treatment
Oral health-related quality of life
Time frame: 9 months after treatment
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Mar 2023.
- Background- 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.
- Derived from this study: PubMed 42433105Chatzopoulos GS, Kaklamanos EG, Vouros I, Mikrogeorgis G, Doufexi AE, Tsalikis L. Clinical, Radiographic and Patient-Centred Outcomes of MINST Versus MIST With Enamel Matrix Derivative in Class II Mandibular Furcation Defects: A Randomised Controlled Trial. J Clin Periodontol. 2026 Jul 11. doi: 10.1111/jcpe.70167. Online ahead of print.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Emdogain® FL (flapless Emdogain®) - Enamel Matrix Derivative and Emdogain® - Enamel Matrix Derivative in people with Periodontal Diseases and Periodontal Disease, AVDC Stage 3, run by Aristotle University Of Thessaloniki at 1 site in Greece.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 7 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Greece. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Georgios S Chatzopoulos, DDS, MS (+30 6970836897, gschatzopoulos@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Periodontal probing pocket depth (PPD) change (time frame: 9 months after treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05541614, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Mar 2023.