Clinical trial NCT04082949: Autologous Fibrin Glue Application as an Adjunct to Nonsurgical Periodontal Treatment of Chronic Periodontitis
Official title: Evaluation of Clinical Effects of Autologous Fibrin Glue Application as an Adjunct to Nonsurgical Periodontal Treatment of Chronic Periodontitis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Chronic Periodontitis
Periodontal Pocket
Periodontal Attachment Loss
Periodontal Diseases
Keywords: Chronic Periodontitis
Autologous fibrin tissue adhesive
Blood Platelets
Non-surgical periodontal therapy
Lead sponsor: Inonu University
Sponsor class: OTHER
First posted: 2019-09-10
Enrollment: 18
Sex: ALL
Minimum age (years): 25
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomised paralleled clinical trial
Primary purpose: SUPPORTIVE_CARE

Brief summary: Chronic periodontitis is an inflammatory and polymicrobic disease characterized by the irreversible loss of alveolar bone and connective tissue attachment of the teeth. Chronic periodontitis is the most prevalent type of periodontitis and it is seen in the great majority of the adult population.

The main objective of periodontal treatment is to heal the inflammatory tissue, to eliminate unhealthy periodontal pockets, and to reduce the number of pathogenic bacteria. The traditional treatment of chronic periodontitis is debridement performed with hand tools and ultrasonic devices. However, in deep pockets, which are difficult to access, mechanical root surface debridement is not sufficient to remove the biofilm via root instrumentation.

The regeneration of the periodontium aims at the reconstitution of the periodontal ligament, alveolar bone, and cementum. Platelet concentrates have gained popularity in regenerative periodontal therapy due to their autologous nature. Their regenerative potential is associated with growth factors such as TGFβ-1, PDGF, EGF, IGF-I, and VEGF, stimulate cell proliferation and regulate matrix remodeling and angiogenesis. Growth factors are naturally occurring proteins that regulate cell growth and development. They also modulate cell proliferation, migration, extracellular matrix formation and other cellular functions in epithelization. In addition, some growth factors may function as cell differentiation factors. These functions of the growth factors support epithelization following surgical periodontal treatment and reduce postoperative pain and swelling with their anti-inflammatory properties. Furthermore, studies have reported their antibacterial potentials.

Different platelet concentrates such as platelet-rich plasma (PRP) and platelet-rich fibrin (PRF) are obtained when whole blood is centrifuged at different speeds and for different durations. When the literature is reviewed, it is seen that these platelet concentrates are frequently used in regenerative therapies in dentistry. In 2010, Sohn et al. obtained autologous fibrin glue (AFG), an injectable platelet concentrate, by centrifuging venous blood for two minutes in a special centrifuge device (Medifuge, Silfradent, Italy; 2400-2700 rpm). AFG is used, by mixing it with bone grafts, in the production of sticky bone, which could be an alternative to titanium mesh and bone block procedures that enable grafts to remain more stable in defects.

It was found in the literature review that studies on AFG, which is a second-generation platelet concentrate, are limited in number. It was also found that these studies were conducted on sticky bone, obtained by mixing AFG with bone grafts, and there are no studies in which AFG is used alone to treat periodontal diseases. The purpose of this study is to investigate the effect of AFG, an injectable platelet concentration, on clinical parameters in the nonsurgical treatment of chronic periodontitis.

Detailed description: This randomized controlled clinical study included patients diagnosed with moderate/severe periodontitis who applied to the Department of Periodontology, Faculty of Dentistry, Inonu University. Written consent was received from each patient. Approval was obtained from the Malatya Clinical Research Ethics Committee for our study, which was designed in compliance with the Declaration of Helsinki.

Two random split-mouth groups were formed among the patients. One side of each patient's mouth was administered AFG following SRP (test group), while the other side of the same patient's mouth was administered a placebo drug (control group).

The following periodontal parameters were evaluated in all patients before and after SRP at the 1st, 3rd, and 6th months: probing depth (PD), clinical attachment level (CAL), plaque index (PI), gingival index (GI), and bleeding on probing (BOP) index. Measurements were performed using a Williams probe (Hu-Friedy, Chicago, IL, USA) for all teeth except for the third molars, in 4 regions (mesiobuccal, midbuccal, distobuccal, midlingual) for PI and GI and in 6 regions (mesiobuccal, midbuccal, distobuccal, mesiolingual, midlingual, distolingual) for PD, CAL, and BOP. Clinical attachment level was measured from the enamel-cement border. Following the initial measurement, the regions with ≥5 mm pocket depth were determined. Measurements were performed only in these regions in the 1st, 3rd, and 6th months. The initial pocket depth was considered within two subgroups as regions with 5-6 mm pocket depth and regions with ≥7 mm pocket depth.

Venous blood from each patient (9 mL) was transferred into a tube without any anticoagulant. Following the protocol recommended by Sohn et al., the venous blood collected in the tube was centrifuged in a special centrifuge machine (Medifuge, Silfradent, Italy). The AFG at the top of the tube was collected using an injector.

Nonsurgical periodontal treatments of the patients were completed in two sessions by a periodontology expert.

In the first session, the supragingival calculus was removed, and patients were given oral hygiene training and encouragement. In the second session, the SRP procedure was performed under local anesthesia in the regions in which there were periodontal pockets of ≥5 mm in the quadrants considered as the control and test groups. The test group was administered AFG using a blunt dental injector in the subgingival region, as an adjunct to SRP, while the control group was administered the placebo.

Eligibility criteria: Inclusion Criteria:

* Being diagnosed with moderate/severe chronic periodontitis;
* Being older than 18 years;
* Presence of at least three teeth in each quadrant with ≥5 mm probing pocket; depth and ≥3 mm clinical attachment loss;
* Being systemically healthy;
* Not smoking cigarettes.

Exclusion Criteria:

* Presence of a systemic disease (diabetes, hypertension, coagulopathy, radiotherapy, chemotherapy, etc.);
* Use of any drugs that could influence the results of the study;
* Periodontal treatment in the last six months before the study, or use of antibiotics in the last six months;
* Smoking or alcohol consumption;
* Pregnancy.

Primary outcomes:
measure: change of pocket depths (PD) in millimeters at different time points
timeFrame: Pocket depths were evaluated in all patients at baseline and after SRP at the 1st, 3rd, and 6th months
measure: change of clinical attachment levels (CAL) in millimeters at different time points
timeFrame: clinical attachment levels were evaluated in all patients at baseline and after SRP at the 1st, 3rd, and 6th months
Secondary outcomes:
measure: change of bleeding on probing(BOP) scores in % at different time points
timeFrame: bleeding on probing scores were evaluated in all patients at baseline and after SRP at the 1st, 3rd, and 6th months
measure: change of gingival index(GI) scores in levels at different time points
timeFrame: gingival index scores were evaluated in all patients at baseline and after SRP at the 1st, 3rd, and 6th months
measure: change of plaque index(PI) scores in levels at different time points
timeFrame: plaque index scores were evaluated in all patients bt baseline and after SRP at the 1st, 3rd, and 6th months
Other outcomes:
Locations:
city: Malatya
country: Turkey
facility: Faculty of Dentistry, Department of Periodontology, İnonu University
Study officials:
affiliation: Dr.
name: MUSTAFA Ö USLU, Asst. Prof.
role: STUDY_DIRECTOR
References:
citation: Heitz-Mayfield LJ, Trombelli L, Heitz F, Needleman I, Moles D. A systematic review of the effect of surgical debridement vs non-surgical debridement for the treatment of chronic periodontitis. J Clin Periodontol. 2002;29 Suppl 3:92-102; discussion 160-2. doi: 10.1034/j.1600-051x.29.s3.5.x.
citation: The potential role of growth and differentiation factors in periodontal regeneration. J Periodontol. 1996 May;67(5):545-53.
citation: Abdul Ameer LA, Raheem ZJ, Abdulrazaq SS, Ali BG, Nasser MM, Khairi AWA. The anti-inflammatory effect of the platelet-rich plasma in the periodontal pocket. Eur J Dent. 2018 Oct-Dec;12(4):528-531. doi: 10.4103/ejd.ejd_49_18.
citation: Kao RT, Murakami S, Beirne OR. The use of biologic mediators and tissue engineering in dentistry. Periodontol 2000. 2009;50:127-53. doi: 10.1111/j.1600-0757.2008.00287.x. No abstract available.
citation: Nevins M, Giannobile WV, McGuire MK, Kao RT, Mellonig JT, Hinrichs JE, McAllister BS, Murphy KS, McClain PK, Nevins ML, Paquette DW, Han TJ, Reddy MS, Lavin PT, Genco RJ, Lynch SE. Platelet-derived growth factor stimulates bone fill and rate of attachment level gain: results of a large multicenter randomized controlled trial. J Periodontol. 2005 Dec;76(12):2205-15. doi: 10.1902/jop.2005.76.12.2205.