PeriodontitisNCT05447026
The Effect of Adjunctive Therapies in Regenerative Treatment of Stage III Grade C Periodontitis
A study testing Antimicrobial photodynamic therapy (aPDT) group, LED photobiomodulation group and Topical ozone group in people with Periodontitis and Lasers, run by Gazi University at 1 site in Turkey (Türkiye).
Trial summary
Anti-infective procedures play a very important role in the success of regenerative surgical treatment of aggressive periodontitis, Grade C periodontitis, which shows the newly named molar-incisor pattern according to the 2017 World Workshop Classification of Periodontal Diseases. Read more about this study
- Who is it for?
- Ages 18 to 35 yearsHealthy volunteers can take part
- Conditions the study is for
- Periodontitis, Lasers, Ozone
- What is being tested?
- Antimicrobial photodynamic therapy (aPDT) group, LED photobiomodulation group and Topical ozone group
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 48 participants
- Where
- 1 siteTurkey (Türkiye)
- Study dates
- 1 Jan 2018to 15 Sep 2022
- 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 to 35 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- the presence of ≥ 20 teeth (excluding third molars);
- the presence of infrabony defects of ≥ 3 mm as detected in periapical radiographs;
- have not received any periodontal treatment and have not taken any of antibiotics within the last 6 months.
Who cannot join
- females that were pregnant or breastfeeding;
- systemic disease that could affect the risk or progression of periodontal disease (e.g., diabetes mellitus, bone metabolic disease, blood disorders, radiation or immuno-suppressive therapy);
- medications that significantly impact periodontal inflammation and bone metabolism (nonsteroidal anti-inflammatory drugs, bisphosphonates, selective serotonin reuptake inhibitors [SSRIs], proton pump inhibitors [PPIs], calcium channel blockers (CCBs), benzodiazepines, or corticosteroids);
- smokers or use of other tobacco products;
- teeth with class III furcation lesions or mobility degree >1;
- systemic antimicrobial treatment (up to 3 weeks prior study inclusion);
- periodontal treatment within the past 6 months prior to recruitment.
Trial locations and contacts
1 site in 1 country.
Turkey (Türkiye)1 site
Gazi University, Faculty of Dentistry
Ankara, 06500
About this study
Official title: The Adjunctive Use of Antimicrobial Photodynamic Therapy, Light-emitting-diode Photobiomodulation, and Ozone Therapy in Regenerative Treatment of Stage III Grade C Periodontitis
Anti-infective procedures play a very important role in the success of regenerative surgical treatment of aggressive periodontitis, Grade C periodontitis, which shows the newly named molar-incisor pattern according to the 2017 World Workshop Classification of Periodontal Diseases. In the present study, it was aimed to analyze the effects of photodynamic, photobiomodulation, and ozone therapy applications on periodontal healing, both clinically and immunologically, in addition to the surgical regenerative treatment of aggressive periodontitis. Forty adult individuals diagnosed with aggressive periodontitis who applied to Gazi University Faculty of Dentistry Department of Periodontology for the treatment of periodontal disease were included in the study. In addition to the regenerative surgical treatment using cortico-cancellous particle allograft and a resorbable collagen membrane in randomly determined areas with multiple intraosseous defects, topical ozone, antimicrobial photodynamic, and light-emitting diode (LED) photobiomodulation treatments were applied. Periodontal clinical parameters [plaque index (PI), gingival index (GI), bleeding on probing (BOP), probing pocket depths (PPD), clinical attachment level (CAL), gingival recession (GR), and width of keratinized gingival (WKG)] were examined and patient-centered postoperative evaluations, and early wound healing index (EHI) assessments were performed for 2 weeks after the operation. In addition, gingival crevicular fluid (GCF) samples from patients to determine the total amount and concentration of vascular endothelial growth factor (VEGF), interleukin -6 (IL-6), Runt-related transcription factor 2 (RunX2), NEL-like 1 (Nell-1), Osterix and samples were quantified by Quantitative Real-Time PCR. The repeated measures ANOVA model was used for the analysis of variables in which both group and time measurements were taken.
Read the detailed description
Periodontitis is a chronic multifactorial inflammatory disease driven by the dysbiotic relationship between the host immune-inflammatory response and the commensal oral microbiota in plaque biofilms that results in the progressive destruction of the tooth-supporting apparatus (Papapanou et al., 2018). Several modifiable and non-modifiable factors including genetic, environmental, and systemic factors can influence its pathogenicity and alter patient's susceptibility to the development and severity of the periodontal disease (Kinane et al., 2017).
According to the 2017 World Workshop classification, stages III or IV, grade C periodontitis, formerly defined as aggressive periodontitis, is characterized by the rapid progression of a particularly severe form of periodontal disease (Papapanou et al., 2018). According to the EFP S3 Clinical Treatment Guidelines, in patients with deep periodontal pockets (≥ 6 mm) step 2 of periodontal therapy (subgingival instrumentation, with or without adjunctive therapies) may be insufficient, and step 3 of surgical periodontal therapy incorporated with regenerative procedures may be required to eliminate deep residual pockets and reconstruct the intrabony part of the defects, as well as prevent tooth loss (Sanz et al., 2020). Despite of some limitations of access flap periodontal surgeries such as increased risk of gingival recession, increased postoperative dentin hypersensitivity, and morbidity, regenerative surgical procedures have been shown to be efficacious for the treatment of intrabony defects in patients with severe periodontitis, with the rapid rate of progression (Diaz-Faes et al., 2020). To improve the outcomes of therapy in severe periodontitis patients, adjunctive interventions such as local or systemic antibiotics, and antimicrobial photodynamic or photobiomodulation therapies using lasers or light-emitting-diodes (LED) have been explored in non-surgical and surgical treatment approaches (Collins et al., 2022; Andere et al., 2022; Giannelli et al., 2018).
Within the visible red or near-infrared (NIR) range of the spectrum (600 to 700 nm and 780 to 1100 nm), low-level lasers (LLL) or LEDs have been widely utilized as an adjunct therapy for periodontitis treatment based on their photobiomodulation and decontamination effects, which primarily occur at the level of the cellular respiratory chain (Zhao et al., 2021). These modalities promote mitochondrial activity and activate the mechanisms, i.e., inducing intracellular metabolic changes, enhancing the cellular resuscitation system, increasing adenosine triphosphate (ATP) and extracellular matrix (ECM) production (Heidari et al., 2018). Through the biological characteristics of these approaches, various studies have shown to increase angiogenesis, promote modulation of the immunoinflammatory response, stimulate the processes of regeneration and epithelialization, and reduce postoperative symptoms. The use of LLLs or LEDs in conjunction with photosensitizing agents (optical absorption-dye) has been referred as antimicrobial photodynamic therapy (aPDT). This procedure stimulates the dye to form free radicals of singlet oxygen that will act as toxic to the target cells or bacteria mainly as a result of deterioration to the cytoplasmic membrane and DNA, thereby demonstrating anti-microbial activity at periodontal pathogenic bacteria in combination with periodontal treatment (Katsikanis et al., 2020). Similar to the biostimulatory features of LLLs or LEDs, adjunctive gaseous ozone therapy applications have been recently exploited because of their analgesic, immunomodulatory, and anti-inflammatory effects, which may have the ability to provide significant added benefits in both step 2 and 3 of the periodontal therapy due to its analgesic, immunomodulatory, and anti-inflammatory effects (Rapone et al., 2022). All these adjunct therapies have also been shown to have a positive effect on the proliferation and osteogenic differentiation of undifferentiated periodontal tissue cells or the direct stimulation of osteoblasts in several studies. However, little information exists regarding the efficacy of these modalities adjunct to the periodontal regenerative therapies on the processes and sequences of the healing and consequently, in the postoperative expression levels of biomarkers of inflammation, angiogenesis, and osteogenesis. Therefore, the objectives of the present study were: (i) to investigate the additional influence of multiple sessions of aPDT, LED photobiomodulation, and topical gaseous ozone therapy applications associated with surgical regenerative treatments by using an allogenic bone graft in combination with a collagen membrane on clinical and patient-centered outcomes in patients with stage III, grade C periodontitis, and (ii) to analyze mRNA expression levels of vascular endothelial growth factor (VEGF), interleukin -6 (IL-6), runt-related transcription factor 2 (RunX2), NEL-like 1 (Nell-1), and osterix in gingival crevicular (GCF) samples at baseline and the 1-, 3- and 6-month follow-ups after the treatment procedures.
- Conditions
- Periodontitis, Lasers, Ozone, Wound Healing, Regeneration
- Being tested
- Control group, Antimicrobial photodynamic therapy (aPDT) group, LED photobiomodulation group, Topical ozone group
- Medical subject headings
- Periodontitis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Control groupDevice
Following local anesthesia, a full-thickness (muco-periosteal) access flap was elevated, granulation tissue was removed and direct instrumentation of the affected root surfaces was performed under the saline irrigation. Intrabony defects were filled with granules of allograft bone material and covered with a native porcine pericardial collagen membrane. The flaps were repositioned and sutured without any tension in order to achieve primary closure of the inter-dental area using a 5-0 mono-filament non-resorbable PTEF suturing material. On the 1st, 3rd, and 7th postoperative days, the sites in the control group received only saline irrigation for 1 min.
Antimicrobial photodynamic therapy (aPDT) groupDevice
Following local anesthesia, a full-thickness (muco-periosteal) access flap was elevated, granulation tissue was removed and direct instrumentation of the affected root surfaces was performed under the saline irrigation. Intrabony defects were filled with granules of allograft bone material and covered with a native porcine pericardial collagen membrane. The flaps were repositioned and sutured without any tension in order to achieve primary closure of the inter-dental area using a 5-0 mono-filament non-resorbable PTEF suturing material. On the 1st, 3rd, and 7th postoperative days, aPDT group received additional application of a diode laser with a wavelength of 810 nm and a power rating of 200 mW (continuous mode). Indocyanine-green (ICG) as a photosensitizer at a concentration of 1 mg/ml was applied at the surgical site on both the buccal and the lingual sides of the flaps. Irradiation was performed in non-contact mode in a constant distance of 1 mm during 30 s per site
LED photobiomodulation groupDevice
Following local anesthesia, a full-thickness (muco-periosteal) access flap was elevated, granulation tissue was removed and direct instrumentation of the affected root surfaces was performed under the saline irrigation. Intrabony defects were filled with granules of allograft bone material and covered with a native porcine pericardial collagen membrane. The flaps were repositioned and sutured without any tension in order to achieve primary closure of the inter-dental area using a 5-0 mono-filament non-resorbable PTEF suturing material. On the 1st, 3rd, and 7th postoperative days, irradiation was carried out with a LED device with a wavelength of 626 nm in the near-infrared region at a dose of 20 mw/cm2 for 20 min with a total energy of 222 J
Topical ozone groupDevice
Following local anesthesia, a full-thickness (muco-periosteal) access flap was elevated, granulation tissue was removed and direct instrumentation of the affected root surfaces was performed under the saline irrigation. Intrabony defects were filled with granules of allograft bone material and covered with a native porcine pericardial collagen membrane. The flaps were repositioned and sutured without any tension in order to achieve primary closure of the inter-dental area using a 5-0 mono-filament non-resorbable PTEF suturing material. On the 1st, 3rd, and 7th postoperative days, topical ozone group received ozone application with an ozone generator at 80% concentration using probe #3 for 30 s per site
| Study group | Role | What they receive |
|---|---|---|
| Control group | Active comparator | Regenerative surgical treatment of periodontal infrabony defects without any adjunctive therapies. Receives: Device: Control group |
| antimicrobial photodynamic therapy (aPDT) group | Active comparator | Regenerative surgical treatment of periodontal infrabony defects in conjunction with irradiation by a diode laser and a photosensitizer Receives: Device: Antimicrobial photodynamic therapy (aPDT) group |
| LED photobiomodulation group | Active comparator | Regenerative surgical treatment of periodontal infrabony defects in conjunction with irradiation by a LED device Receives: Device: LED photobiomodulation group |
| Topical ozone group | Active comparator | Regenerative surgical treatment of periodontal infrabony defects in conjunction with topical ozone application Receives: Device: Topical ozone group |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes in CAL values
The changes in the mean CAL values between baseline and postoperative 6 months
Measured: 6 months after the surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Jul 2022
- Study start1 Jan 2018
- Primary completion10 Feb 2022
- Study completion15 Sep 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (11)Papers the sponsor has linked to this study.
- Other trials for PeriodontitisStudies of the same condition, open and under way.
- More trials run by Gazi UniversityThe 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
- The present study is a parallel design randomized controlled clinical trial evaluating four different treatment approaches.
- Masking
- Single blind
- Who is masked
- Investigator
- Enrolment
- 48 participants (actual)
Sponsor and investigators
- Lead sponsor
- Gazi University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Sıla Çağrı İşler, Gazi University
- Investigators
- Deniz Ozbay, Prof Dr, Study director, Gazi University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05447026
- Sponsor's protocol ID
- 36290600/105
- Status last verified
- Aug 2023
- First submitted
- 1 Jul 2022
- Last updated
- 30 Aug 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Kinane DF, Stathopoulou PG, Papapanou PN. Periodontal diseases. Nat Rev Dis Primers. 2017 Jun 22;3:17038. doi: 10.1038/nrdp.2017.38.
PubMed 28805207Papapanou PN, Sanz M, Buduneli N, Dietrich T, Feres M, Fine DH, Flemmig TF, Garcia R, Giannobile WV, Graziani F, Greenwell H, Herrera D, Kao RT, Kebschull M, Kinane DF, Kirkwood KL, Kocher T, Kornman KS, Kumar PS, Loos BG, Machtei E, Meng H, Mombelli A, Needleman I, Offenbacher S, Seymour GJ, Teles R, Tonetti MS. Periodontitis: Consensus report of workgroup 2 of the 2017 World Workshop on the Classification of Periodontal and Peri-Implant Diseases and Conditions. J Periodontol. 2018 Jun;89 Suppl 1:S173-S182. doi: 10.1002/JPER.17-0721.
PubMed 29926951Sanz M, Herrera D, Kebschull M, Chapple I, Jepsen S, Beglundh T, Sculean A, Tonetti MS; EFP Workshop Participants and Methodological Consultants. Treatment of stage I-III periodontitis-The EFP S3 level clinical practice guideline. J Clin Periodontol. 2020 Jul;47 Suppl 22(Suppl 22):4-60. doi: 10.1111/jcpe.13290.
PubMed 32383274Diaz-Faes L, Fernandez-Somoano A, Magan-Fernandez A, Mesa F. Efficacy of regenerative therapy in aggressive periodontitis: a systematic review and meta-analysis of randomised controlled clinical trials. Clin Oral Investig. 2020 Apr;24(4):1369-1378. doi: 10.1007/s00784-020-03237-0. Epub 2020 Feb 14.
PubMed 32060656Collins JR, Ogando G, Gonzalez R, Figuero E, Marin MJ, Sanz M, Herrera D. Adjunctive efficacy of systemic metronidazole in the surgical treatment of periodontitis: a double-blind parallel randomized clinical trial. Clin Oral Investig. 2022 May;26(5):4195-4207. doi: 10.1007/s00784-022-04392-2. Epub 2022 Feb 5.
PubMed 35122549Andere NMRB, Castro Dos Santos NC, Araujo CF, Paz HES, Shaddox LM, Casarin RCV, Santamaria MP. Open flap debridement compared to repeated applications of photodynamic therapy in the treatment of residual pockets: A randomized clinical trial. J Periodontol. 2022 Nov;93(11):1671-1681. doi: 10.1002/JPER.22-0059. Epub 2022 Jun 2.
PubMed 35536044Giannelli M, Materassi F, Fossi T, Lorenzini L, Bani D. Treatment of severe periodontitis with a laser and light-emitting diode (LED) procedure adjunctive to scaling and root planing: a double-blind, randomized, single-center, split-mouth clinical trial investigating its efficacy and patient-reported outcomes at 1 year. Lasers Med Sci. 2018 Jul;33(5):991-1002. doi: 10.1007/s10103-018-2441-9. Epub 2018 Jan 18.
PubMed 29349511Zhao H, Hu J, Zhao L. The effect of low-level laser therapy as an adjunct to periodontal surgery in the management of postoperative pain and wound healing: a systematic review and meta-analysis. Lasers Med Sci. 2021 Feb;36(1):175-187. doi: 10.1007/s10103-020-03072-5. Epub 2020 Jul 1.
PubMed 32613416Heidari M, Fekrazad R, Sobouti F, Moharrami M, Azizi S, Nokhbatolfoghahaei H, Khatami M. Evaluating the effect of photobiomodulation with a 940-nm diode laser on post-operative pain in periodontal flap surgery. Lasers Med Sci. 2018 Nov;33(8):1639-1645. doi: 10.1007/s10103-018-2492-y. Epub 2018 Jul 6.
PubMed 29978268Katsikanis F, Strakas D, Vouros I. The application of antimicrobial photodynamic therapy (aPDT, 670 nm) and diode laser (940 nm) as adjunctive approach in the conventional cause-related treatment of chronic periodontal disease: a randomized controlled split-mouth clinical trial. Clin Oral Investig. 2020 May;24(5):1821-1827. doi: 10.1007/s00784-019-03045-1. Epub 2019 Aug 13.
PubMed 31410672Rapone B, Ferrara E, Santacroce L, Topi S, Gnoni A, Dipalma G, Mancini A, Di Domenico M, Tartaglia GM, Scarano A, Inchingolo F. The Gaseous Ozone Therapy as a Promising Antiseptic Adjuvant of Periodontal Treatment: A Randomized Controlled Clinical Trial. Int J Environ Res Public Health. 2022 Jan 16;19(2):985. doi: 10.3390/ijerph19020985.
PubMed 35055807
Study at a glance
From the registry record, last updated by the sponsor on 30 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Adjunctive Use of Antimicrobial Photodynamic Therapy, Light-emitting-diode Photobiomodulation, and Ozone Therapy in Regenerative Treatment of Stage III Grade C Periodontitis
- ClinicalTrials.gov ID
- NCT05447026
- Acronym / sponsor ID
- 36290600/105
- Conditions
- Periodontitis, Lasers, Ozone, Wound Healing, Regeneration
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 48 participants (actual)
- Lead sponsor
- Gazi UniversityUniversity, hospital or other
- Study start
- 1 Jan 2018 (actual)
- Primary completion
- 10 Feb 2022 (actual)
- Study completion
- 15 Sep 2022 (actual)
- First posted
- 7 Jul 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.
Anti-infective procedures play a very important role in the success of regenerative surgical treatment of aggressive periodontitis, Grade C periodontitis, which shows the newly named molar-incisor pattern according to the 2017 World Workshop Classification of Periodontal Diseases. In the present study, it was aimed to analyze the effects of photodynamic, photobiomodulation, and ozone therapy applications on periodontal healing, both clinically and immunologically, in addition to the surgical regenerative treatment of aggressive periodontitis. Forty adult individuals diagnosed with aggressive periodontitis who applied to Gazi University Faculty of Dentistry Department of Periodontology for the treatment of periodontal disease were included in the study. In addition to the regenerative surgical treatment using cortico-cancellous particle allograft and a resorbable collagen membrane in randomly determined areas with multiple intraosseous defects, topical ozone, antimicrobial photodynamic, and light-emitting diode (LED) photobiomodulation treatments were applied. Periodontal clinical parameters [plaque index (PI), gingival index (GI), bleeding on probing (BOP), probing pocket depths (PPD), clinical attachment level (CAL), gingival recession (GR), and width of keratinized gingival (WKG)] were examined and patient-centered postoperative evaluations, and early wound healing index (EHI) assessments were performed for 2 weeks after the operation. In addition, gingival crevicular fluid (GCF) samples from patients to determine the total amount and concentration of vascular endothelial growth factor (VEGF), interleukin -6 (IL-6), Runt-related transcription factor 2 (RunX2), NEL-like 1 (Nell-1), Osterix and samples were quantified by Quantitative Real-Time PCR. The repeated measures ANOVA model was used for the analysis of variables in which both group and time measurements were taken.
Detailed description
Periodontitis is a chronic multifactorial inflammatory disease driven by the dysbiotic relationship between the host immune-inflammatory response and the commensal oral microbiota in plaque biofilms that results in the progressive destruction of the tooth-supporting apparatus (Papapanou et al., 2018). Several modifiable and non-modifiable factors including genetic, environmental, and systemic factors can influence its pathogenicity and alter patient's susceptibility to the development and severity of the periodontal disease (Kinane et al., 2017).
According to the 2017 World Workshop classification, stages III or IV, grade C periodontitis, formerly defined as aggressive periodontitis, is characterized by the rapid progression of a particularly severe form of periodontal disease (Papapanou et al., 2018). According to the EFP S3 Clinical Treatment Guidelines, in patients with deep periodontal pockets (≥ 6 mm) step 2 of periodontal therapy (subgingival instrumentation, with or without adjunctive therapies) may be insufficient, and step 3 of surgical periodontal therapy incorporated with regenerative procedures may be required to eliminate deep residual pockets and reconstruct the intrabony part of the defects, as well as prevent tooth loss (Sanz et al., 2020). Despite of some limitations of access flap periodontal surgeries such as increased risk of gingival recession, increased postoperative dentin hypersensitivity, and morbidity, regenerative surgical procedures have been shown to be efficacious for the treatment of intrabony defects in patients with severe periodontitis, with the rapid rate of progression (Diaz-Faes et al., 2020). To improve the outcomes of therapy in severe periodontitis patients, adjunctive interventions such as local or systemic antibiotics, and antimicrobial photodynamic or photobiomodulation therapies using lasers or light-emitting-diodes (LED) have been explored in non-surgical and surgical treatment approaches (Collins et al., 2022; Andere et al., 2022; Giannelli et al., 2018).
Within the visible red or near-infrared (NIR) range of the spectrum (600 to 700 nm and 780 to 1100 nm), low-level lasers (LLL) or LEDs have been widely utilized as an adjunct therapy for periodontitis treatment based on their photobiomodulation and decontamination effects, which primarily occur at the level of the cellular respiratory chain (Zhao et al., 2021). These modalities promote mitochondrial activity and activate the mechanisms, i.e., inducing intracellular metabolic changes, enhancing the cellular resuscitation system, increasing adenosine triphosphate (ATP) and extracellular matrix (ECM) production (Heidari et al., 2018). Through the biological characteristics of these approaches, various studies have shown to increase angiogenesis, promote modulation of the immunoinflammatory response, stimulate the processes of regeneration and epithelialization, and reduce postoperative symptoms. The use of LLLs or LEDs in conjunction with photosensitizing agents (optical absorption-dye) has been referred as antimicrobial photodynamic therapy (aPDT). This procedure stimulates the dye to form free radicals of singlet oxygen that will act as toxic to the target cells or bacteria mainly as a result of deterioration to the cytoplasmic membrane and DNA, thereby demonstrating anti-microbial activity at periodontal pathogenic bacteria in combination with periodontal treatment (Katsikanis et al., 2020). Similar to the biostimulatory features of LLLs or LEDs, adjunctive gaseous ozone therapy applications have been recently exploited because of their analgesic, immunomodulatory, and anti-inflammatory effects, which may have the ability to provide significant added benefits in both step 2 and 3 of the periodontal therapy due to its analgesic, immunomodulatory, and anti-inflammatory effects (Rapone et al., 2022). All these adjunct therapies have also been shown to have a positive effect on the proliferation and osteogenic differentiation of undifferentiated periodontal tissue cells or the direct stimulation of osteoblasts in several studies. However, little information exists regarding the efficacy of these modalities adjunct to the periodontal regenerative therapies on the processes and sequences of the healing and consequently, in the postoperative expression levels of biomarkers of inflammation, angiogenesis, and osteogenesis. Therefore, the objectives of the present study were: (i) to investigate the additional influence of multiple sessions of aPDT, LED photobiomodulation, and topical gaseous ozone therapy applications associated with surgical regenerative treatments by using an allogenic bone graft in combination with a collagen membrane on clinical and patient-centered outcomes in patients with stage III, grade C periodontitis, and (ii) to analyze mRNA expression levels of vascular endothelial growth factor (VEGF), interleukin -6 (IL-6), runt-related transcription factor 2 (RunX2), NEL-like 1 (Nell-1), and osterix in gingival crevicular (GCF) samples at baseline and the 1-, 3- and 6-month follow-ups after the treatment procedures.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (investigator)
- Number of arms
- 4
- Model description
- The present study is a parallel design randomized controlled clinical trial evaluating four different treatment approaches.
| Arm | Type | Receives |
|---|---|---|
| Control group | Active comparator | Device: Control groupRegenerative surgical treatment of periodontal infrabony defects without any adjunctive therapies. |
| antimicrobial photodynamic therapy (aPDT) group | Active comparator | Device: Antimicrobial photodynamic therapy (aPDT) groupRegenerative surgical treatment of periodontal infrabony defects in conjunction with irradiation by a diode laser and a photosensitizer |
| LED photobiomodulation group | Active comparator | Device: LED photobiomodulation groupRegenerative surgical treatment of periodontal infrabony defects in conjunction with irradiation by a LED device |
| Topical ozone group | Active comparator | Device: Topical ozone groupRegenerative surgical treatment of periodontal infrabony defects in conjunction with topical ozone application |
Who may qualify
- Ages
- 18 to 35 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- the presence of ≥ 20 teeth (excluding third molars);
- the presence of infrabony defects of ≥ 3 mm as detected in periapical radiographs;
- have not received any periodontal treatment and have not taken any of antibiotics within the last 6 months.
Key exclusion criteria (7 listed)
- females that were pregnant or breastfeeding;
- systemic disease that could affect the risk or progression of periodontal disease (e.g., diabetes mellitus, bone metabolic disease, blood disorders, radiation or immuno-suppressive therapy);
- medications that significantly impact periodontal inflammation and bone metabolism (nonsteroidal anti-inflammatory drugs, bisphosphonates, selective serotonin reuptake inhibitors [SSRIs], proton pump inhibitors [PPIs], calcium channel blockers (CCBs), benzodiazepines, or corticosteroids);
- smokers or use of other tobacco products;
- teeth with class III furcation lesions or mobility degree >1;
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 |
|---|---|---|
| Control groupFollowing local anesthesia, a full-thickness (muco-periosteal) access flap was elevated, granulation tissue was removed and direct instrumentation of the affected root surfaces was performed under the saline irrigation. Intrabony defects were filled with granules of allograft bone material and covered with a native porcine pericardial collagen membrane. The flaps were repositioned and sutured without any tension in order to achieve primary closure of the inter-dental area using a 5-0 mono-filament non-resorbable PTEF suturing material. On the 1st, 3rd, and 7th postoperative days, the sites in the control group received only saline irrigation for 1 min. | Device | Control group |
| Antimicrobial photodynamic therapy (aPDT) groupFollowing local anesthesia, a full-thickness (muco-periosteal) access flap was elevated, granulation tissue was removed and direct instrumentation of the affected root surfaces was performed under the saline irrigation. Intrabony defects were filled with granules of allograft bone material and covered with a native porcine pericardial collagen membrane. The flaps were repositioned and sutured without any tension in order to achieve primary closure of the inter-dental area using a 5-0 mono-filament non-resorbable PTEF suturing material. On the 1st, 3rd, and 7th postoperative days, aPDT group received additional application of a diode laser with a wavelength of 810 nm and a power rating of 200 mW (continuous mode). Indocyanine-green (ICG) as a photosensitizer at a concentration of 1 mg/ml was applied at the surgical site on both the buccal and the lingual sides of the flaps. Irradiation was performed in non-contact mode in a constant distance of 1 mm during 30 s per site | Device | antimicrobial photodynamic therapy (aPDT) group |
| LED photobiomodulation groupFollowing local anesthesia, a full-thickness (muco-periosteal) access flap was elevated, granulation tissue was removed and direct instrumentation of the affected root surfaces was performed under the saline irrigation. Intrabony defects were filled with granules of allograft bone material and covered with a native porcine pericardial collagen membrane. The flaps were repositioned and sutured without any tension in order to achieve primary closure of the inter-dental area using a 5-0 mono-filament non-resorbable PTEF suturing material. On the 1st, 3rd, and 7th postoperative days, irradiation was carried out with a LED device with a wavelength of 626 nm in the near-infrared region at a dose of 20 mw/cm2 for 20 min with a total energy of 222 J | Device | LED photobiomodulation group |
| Topical ozone groupFollowing local anesthesia, a full-thickness (muco-periosteal) access flap was elevated, granulation tissue was removed and direct instrumentation of the affected root surfaces was performed under the saline irrigation. Intrabony defects were filled with granules of allograft bone material and covered with a native porcine pericardial collagen membrane. The flaps were repositioned and sutured without any tension in order to achieve primary closure of the inter-dental area using a 5-0 mono-filament non-resorbable PTEF suturing material. On the 1st, 3rd, and 7th postoperative days, topical ozone group received ozone application with an ozone generator at 80% concentration using probe #3 for 30 s per site | Device | Topical ozone group |
Primary outcome
Changes in CAL values
Time frame: 6 months after the surgery
The changes in the mean CAL values between baseline and postoperative 6 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Aug 2023.
- Results publication: PubMed 28805207Kinane DF, Stathopoulou PG, Papapanou PN. Periodontal diseases. Nat Rev Dis Primers. 2017 Jun 22;3:17038. doi: 10.1038/nrdp.2017.38.
- Results publication: PubMed 29926951Papapanou PN, Sanz M, Buduneli N, Dietrich T, Feres M, Fine DH, Flemmig TF, Garcia R, Giannobile WV, Graziani F, Greenwell H, Herrera D, Kao RT, Kebschull M, Kinane DF, Kirkwood KL, Kocher T, Kornman KS, Kumar PS, Loos BG, Machtei E, Meng H, Mombelli A, Needleman I, Offenbacher S, Seymour GJ, Teles R, Tonetti MS. Periodontitis: Consensus report of workgroup 2 of the 2017 World Workshop on the Classification of Periodontal and Peri-Implant Diseases and Conditions. J Periodontol. 2018 Jun;89 Suppl 1:S173-S182. doi: 10.1002/JPER.17-0721.
- Results publication: PubMed 32383274Sanz M, Herrera D, Kebschull M, Chapple I, Jepsen S, Beglundh T, Sculean A, Tonetti MS; EFP Workshop Participants and Methodological Consultants. Treatment of stage I-III periodontitis-The EFP S3 level clinical practice guideline. J Clin Periodontol. 2020 Jul;47 Suppl 22(Suppl 22):4-60. doi: 10.1111/jcpe.13290.
- Results publication: PubMed 32060656Diaz-Faes L, Fernandez-Somoano A, Magan-Fernandez A, Mesa F. Efficacy of regenerative therapy in aggressive periodontitis: a systematic review and meta-analysis of randomised controlled clinical trials. Clin Oral Investig. 2020 Apr;24(4):1369-1378. doi: 10.1007/s00784-020-03237-0. Epub 2020 Feb 14.
- Results publication: PubMed 35122549Collins JR, Ogando G, Gonzalez R, Figuero E, Marin MJ, Sanz M, Herrera D. Adjunctive efficacy of systemic metronidazole in the surgical treatment of periodontitis: a double-blind parallel randomized clinical trial. Clin Oral Investig. 2022 May;26(5):4195-4207. doi: 10.1007/s00784-022-04392-2. Epub 2022 Feb 5.
- Results publication: PubMed 35536044Andere NMRB, Castro Dos Santos NC, Araujo CF, Paz HES, Shaddox LM, Casarin RCV, Santamaria MP. Open flap debridement compared to repeated applications of photodynamic therapy in the treatment of residual pockets: A randomized clinical trial. J Periodontol. 2022 Nov;93(11):1671-1681. doi: 10.1002/JPER.22-0059. Epub 2022 Jun 2.
- Results publication: PubMed 29349511Giannelli M, Materassi F, Fossi T, Lorenzini L, Bani D. Treatment of severe periodontitis with a laser and light-emitting diode (LED) procedure adjunctive to scaling and root planing: a double-blind, randomized, single-center, split-mouth clinical trial investigating its efficacy and patient-reported outcomes at 1 year. Lasers Med Sci. 2018 Jul;33(5):991-1002. doi: 10.1007/s10103-018-2441-9. Epub 2018 Jan 18.
- Results publication: PubMed 32613416Zhao H, Hu J, Zhao L. The effect of low-level laser therapy as an adjunct to periodontal surgery in the management of postoperative pain and wound healing: a systematic review and meta-analysis. Lasers Med Sci. 2021 Feb;36(1):175-187. doi: 10.1007/s10103-020-03072-5. Epub 2020 Jul 1.
- Results publication: PubMed 29978268Heidari M, Fekrazad R, Sobouti F, Moharrami M, Azizi S, Nokhbatolfoghahaei H, Khatami M. Evaluating the effect of photobiomodulation with a 940-nm diode laser on post-operative pain in periodontal flap surgery. Lasers Med Sci. 2018 Nov;33(8):1639-1645. doi: 10.1007/s10103-018-2492-y. Epub 2018 Jul 6.
- Results publication: PubMed 31410672Katsikanis F, Strakas D, Vouros I. The application of antimicrobial photodynamic therapy (aPDT, 670 nm) and diode laser (940 nm) as adjunctive approach in the conventional cause-related treatment of chronic periodontal disease: a randomized controlled split-mouth clinical trial. Clin Oral Investig. 2020 May;24(5):1821-1827. doi: 10.1007/s00784-019-03045-1. Epub 2019 Aug 13.
- Results publication: PubMed 35055807Rapone B, Ferrara E, Santacroce L, Topi S, Gnoni A, Dipalma G, Mancini A, Di Domenico M, Tartaglia GM, Scarano A, Inchingolo F. The Gaseous Ozone Therapy as a Promising Antiseptic Adjuvant of Periodontal Treatment: A Randomized Controlled Clinical Trial. Int J Environ Res Public Health. 2022 Jan 16;19(2):985. doi: 10.3390/ijerph19020985.
- Individual participant dataSharing planned: No
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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.
Deniz Ozbay, Prof Dr study director
Gazi University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Antimicrobial photodynamic therapy (aPDT) group, LED photobiomodulation group and Topical ozone group in people with Periodontitis and Lasers, run by Gazi University at 1 site in Turkey (Türkiye).
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 3 inclusion and 7 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: finished, as of the sponsor's last update on 30 Aug 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 Turkey (Türkiye). 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Changes in CAL values (time frame: 6 months after the surgery). 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 NCT05447026, which also lists 11 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 30 Aug 2023.