Periodontitis
Conditions
Keywords
Clinical Trial, Periodontitis, Wound Healing, Polynucleotides, Hyaluronic Acid
Brief summary
Over the last 30 years, the prevalence of periodontitis (PE) has increased substantially, including among younger populations, highlighting the need to improve the management of this condition as a chronic disease and to develop techniques that favor its control and stability in the short and long term. After non-surgical periodontal therapy (NSPT), the first phase of PE treatment, residual periodontal pockets may persist, often associated with intraosseous defects, which compromise the tooth's prognosis and are associated with disease progression and increased treatment complexity. Surgical treatment of intrabony defects often results in the formation of long junctional epithelium, weakly attached to the root surface, since true regeneration of periodontal tissues is an unpredictable event and depends on complex biological processes. In recent decades, various biomaterials have been proposed as aids to open-flap debridement (OFD) in the surgical treatment of intrabony defects, with the aim of promoting periodontal regeneration, enhancing clinical results and favoring treatment prognosis. Recently, the combination of polynucleotides (PN) and hyaluronic acid (HA) has emerged as a promising auxiliary strategy to promote periodontal regeneration, due to its biological potential in stimulating cell growth and increasing cell viability. The aim of this controlled, randomized, parallel-group clinical study is to compare OFD alone with its association with xenogenous bone graft or xenogenous bone graft plus gel containing PN/HA in the surgical treatment of intrabony defects in patients with PE (stages III or IV, grades B or C). The patients will be randomly divided into three experimental groups (n=22): control (C), xenogeneic bone graft (XENO) and xenogeneic bone graft plus gel containing PN/HA (R-XENO). The patients will receive NSPT, and after eight weeks will undergo surgical procedures to treat the intrabony defects (baseline). Clinical, radiographic, tomographic and immunological periodontal parameters will be assessed at baseline and after 12 months. The wound healing index will be recorded 1, 2 and 6 weeks after the surgical procedure. Patient-centered outcomes will be assessed by means of a visual analog scale (VAS), applied two weeks after the surgical procedure, and oral health-related quality of life (OHRQoL) questionnaires, applied at the beginning of the study and after 6 and 12 months. At the start of the study and after 6 and 12 months, anthropometric data will be collected, blood pressure (BP) will be measured and questionnaires will be applied to survey socio-demographic and nutritional parameters. The data obtained will be statistically analyzed (p\<0.05).
Detailed description
This controlled, randomized, parallel-group clinical study aims to compare open-flap debridement alone with its association with xenogeneic bone graft or xenogeneic bone graft plus gel containing polynucleotides (PN) and hyaluronic acid (HA) in the surgical treatment of intrabony defects in patients with periodontitis (stages III or IV, grades B or C), based on clinical, immunologic, radiographic/tomographic parameters and patient-centered outcomes. The sample size was calculated using the primary variable clinical attachment level (CAL), considering a mean difference of 1 mm between the experimental groups as the minimum value and a standard deviation of 0.91. Considering β = 80% and α = 5%, the required sample size was 18 patients for each experimental group, with each patient contributing a single defect. Considering a dropout of 20%, the number was increased to 22 patients per experimental group, making a total of 66 patients. Patients who meet the inclusion criteria will be randomly assigned to one of three experimental groups (n=22) in a 1:1 allocation ratio: Group C (Control), including intrabony defects treated with open flap debridement alone; Group XENO, including open flap debridement associated with xenogeneic bone grafting; and Group R-XENO, including open flap debridement associated with xenogeneic bone grafting and a PN/HA-containing gel. Randomization will be performed using software, which will identify each participant by a numerical code. Group allocation will be carried out on the day of surgery by the study coordinator. Surgical treatment: After local anesthesia using an infiltration or nerve block technique with a sterile injectable solution of 2% mepivacaine hydrochloride (20 mg/mL) and 1:100,000 epinephrine (10 µg/mL), intrasulcular incisions will be made on the buccal and lingual/palatal aspects using a 15C surgical blade (Stainless Steel Surgical Blades, Swann-Morton®, Sheffield, England), extending one tooth mesially and one tooth distally to the tooth associated with the defect. A full-thickness flap will be carefully elevated on the buccal and lingual/palatal sides to expose 2 to 3 mm of the alveolar crest. Meticulous debridement of the defect will be performed, along with the removal of subgingival biofilm and calculus using ultrasonic combined with manual instruments, followed by irrigation with sterile saline solution. The defects will be filled as follows: with blood clot only in the group C; with xenogeneic bone graft (Geistlich Bio-Oss®, Geistlich Pharma AG, Wolhusen, Switzerland) in the XENO group; and with xenogeneic bone graft (Geistlich Bio-Oss®) plus PN/HA-containing gel (REGENFAST®, Geistlich Pharma AG, Wolhusen, Switzerland) in the R-XENO group. Primary soft tissue closure was achieved by interrupted mattress suture technique with non-resorbable monofilament polyamide 5-0 sutures (Soft Blue®, Techsuture, Bauru, SP, Brazil). Outcome assessment will be conducted at predefined time points. The primary outcome is clinical attachment level (CAL). Secondary outcomes include probing depth (PD); radiographic and tomographic measures of bone fill and defect resolution; quantitative analysis of biomarkers related to tissue neoformation (PDGF-BB, VEGF, BMP-2); early wound healing assessed by standardized indices; and patient-reported outcomes, including pain perception and oral health-related quality of life.
Interventions
DEVICEPolynucleotide and hyaluronic acid-based gel
The polynucleotide and hyaluronic acid-based gel will be applied in combination with a xenogeneic bone graft to fill the intrabony defects.
OTHERControl
Intrabony defects treated with open flap debridement alone
DEVICEXenogeneic bone graft
The xenogeneic bone graft will be applied to fill the intrabony defects.
Sponsors
University of Sao Paulo
Geistlich Pharma AG
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Intervention model description
Groups: Patients who meet the inclusion criteria will be randomly assigned to one of three experimental groups (n=22) in a 1:1 allocation ratio: Group C (Control), including intrabony defects treated with open flap debridement alone; Group XENO, including open flap debridement associated with xenogeneic bone grafting; and Group R-XENO, including open flap debridement associated with xenogeneic bone grafting and a PN/HA-containing gel. Randomization will be performed using software, which will identify each participant by a numerical code. Group allocation will be carried out on the day of surgery by the study coordinator.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* ≥ 18 years of age; * diagnosis of periodontitis stage III or IV, grade B or C (Chapple et al., 2018; Papapanou et al., 2018); * full-mouth plaque score (FMPS) and full-mouth bleeding score (FMBS) of ≤ 20%; * presence of a 2- or 3-wall intrabony defect with a depth ≥ 3 mm and probing depth and clinical attachment level ≥ 5 mm in the interproximal region of a single- or multi-rooted tooth; * pulp vitality or satisfactory endodontic treatment in the tooth to be treated; * at least 1 mm of keratinized tissue on the buccal surface of the tooth to be treated.
Exclusion criteria
* presence of furcation involvement associated with the intrabony defect; * presence of systemic conditions that may affect the progression of periodontitis or the response to its treatment; * long-term use of anti-inflammatory or immunosuppressive medications; * use of antimicrobials within the last 6 months; * continuous use of mouthwashes containing antimicrobial agents within the last 6 months; * need for prophylactic antibiotic therapy for routine dental procedures; * current or past tobacco use within the last 5 years; * pregnancy; * breastfeeding.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Attachment Level (CAL) | Baseline and 12 months | Distance between the cemento-enamel junction and the bottom of the periodontal pocket/sulcus, in milimeters |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Probing depth (PD) | Baseline and 12 months | Distance between the gingival margin and the bottom of the periodontal pocket/sulcus, in milimeters |
| Changes in the alveolar bone crest | Baseline and 12 months | Distance between the cemento-enamel junction and the alveolar crest in milimeters, assessed radiographically |
| Radiographic defect depth | Baseline and 12 months | Distance between the alveolar crest and the defect base in milimeters, assessed radiographically |
| Vertical bone loss | Baseline and 12 months | Distante between the cemento-enamel junction and the defect base in milimeters, assessed radiographically |
| Tomographic vertical bone loss | Baseline and 12 months | Distance, in milimeters, between the cemento-enamel junction and the defect base in coronal sections of computed tomography |
| Buccolingual width of the defect | Baseline and 12 months | Buccolingual width, in milimeters, assessed in axial sections of computed tomography |
| Platelet-derived growth factor (PDGF)-BB | Baseline and 12 months | Quantification in pg/mL using a multiplex assay with Milliplex plates (Millipore) |
| Vascular endothelial growth factor (VEGF) | Baseline and 12 months | Quantification in pg/mL using a multiplex assay with Milliplex plates (Millipore) |
| Bone morphogenetic protein (BMP)-2 | Baseline and 12 months | Quantification in pg/mL using an enzyme-linked immunosorbent assay (ELISA). |
| Wound Healing Index (WHI). | 1, 2 and 6 weeks | A score from 1 to 3 will be assigned according to the following criteria: i) score 1 - uneventful healing, i.e., no gingival edema, erythema, suppuration, patient discomfort, or flap dehiscence; ii) score 2 - uneventful healing with slight gingival edema, erythema, patient discomfort, or flap dehiscence, but no suppuration; iii) score 3 - poor wound healing, with significant gingival edema, erythema, patient discomfort, flap dehiscence, or any suppuration. |
| Visual Analogue Scale | 2 weeks | Patients will complete a questionnaire using a 100 mm visual analogue scale (VAS) , where 0 means no pain/hardship and 100 means unbearable pain/hardship |
| Oral Health Impact Profile (OHIP-14) questionnaire | Baseline, 6 and 12 months | Oral health-related quality of life assessed using the 14-item Oral Health Impact Profile (OHIP-14) questionnaire. Each item is scored on a 5-point Likert scale ranging from 0 (never) to 4 (very often). The total score is calculated as the sum of all item responses, ranging from 0 to 56, with higher scores indicating worse oral health-related quality of life. |
| Oral Health Related Quality of Life (OHRQoL-UK) questionnaire | Baseline, 6 and 12 months | Oral health-related quality of life assessed using the Oral Health-Related Quality of Life-UK (OHRQoL-UK) questionnaire. The instrument consists of 16 items covering physical, psychological, and social dimensions. Each item is scored on a 5-point scale ranging from 1 (very bad effect) to 5 (very good effect). The total score is calculated as the sum of all item responses, ranging from 16 to 80, with higher scores indicating better oral health-related quality of life. |
Countries
Brazil
Outcome results
None listed