PeriodontitisPhase 3NCT05042024
Supplementation With L-ornithine But Not L-arginine Increases Density of CD68+ and CD163+ Macrophages in Periodontitis
A Phase 3 study testing Scaling and root planing, Oral L-arginine aspartate administration and Oral L-ornithine aspartate administration in people with Periodontitis, run by Ukrainian Medical Stomatological Academy at 1 site in Ukraine.
Trial summary
The aim of the study was to investigate whether oral administration of L-arginine or L-ornithine could modulate local representation density and ratio of macrophages in periodontitis-affected gingiva by using immunohistochemical detection of CD68+ and CD163+ macrophages in biopsies of the gingiva. Read more about this study
- Who is it for?
- Ages 25 to 54 years
- Conditions the study is for
- Periodontitis
- What is being tested?
- Scaling and root planing, Oral L-arginine aspartate administration and Oral L-ornithine aspartate administration
- Type of treatment
- Pill or oral medicine, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 75 participants
- Where
- 1 siteUkraine
- Study dates
- 20 Oct 2017to 1 Nov 2018
- Phase
- Phase 3
- 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 25 to 54 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Presence of periodontitis
- Good general health
- At least 19 remaining teeth
- Written informed consent forms
Who cannot join
- Antibiotics or anti-inflammatory medications use within the preceding 3 months
- Periodontal therapy within the previous 6 months
- Purulent exudation from periodontal pockets
- Pregnancy and breastfeeding
- Presence of severe, uncontrolled (decompensated) diseases of the internal organs, or neuropsychiatric disorders
- Presence of other conditions that determined the inability of the patient to understand the nature and possible consequences of the study
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Supplementation With L-ornithine Increases Representation Density of CD68+ and CD163+ Macrophages in Human Periodontitis Gingiva and Can Modulate Macrophages Phenotypes. Randomized Controlled Pilot Trial
The aim of the study was to investigate whether oral administration of L-arginine or L-ornithine could modulate local representation density and ratio of macrophages in periodontitis-affected gingiva by using immunohistochemical detection of CD68+ and CD163+ macrophages in biopsies of the gingiva.
The null hypothesis tested was that L-arginine and L-ornithine have no influences on CD68+ and CD163+ macrophages densities when supplementing the treatment of periodontitis.
Read more
Materials and methods. 75 individuals with a diagnosis of generalized periodontitis at stages II-III and grade B (38 women and 37 men, 51% and 49%, respectively) were included in the study. Periodontitis was diagnosed by using the criteria of the Classification of Periodontal and Peri-Implant Diseases and Conditions 2017. 25 patients received scaling and root planing only; 25 patients additionally received L-arginine, and 25 - L-ornithine, according to instructions available in Ukraine.
For the immunohistochemical study of paraffin-embedded sections, the gingival biopsy was taken from 5 selected patients per group before treatment and after 1 month. CD68+ (cluster of differentiation 68 positive) and CD163+ cells served as a morphological equivalent of M1, M2 macrophages subpopulations, and their densities were calculated per 10000 μm2. Statistical analysis was performed by adequate power methods.
Read the detailed description
Study design The present work was the original research study. 75 individuals with a diagnosis of generalized periodontitis at stages II-III and grade B (38 women and 37 men, 51% and 49%, respectively) were included in the study. Periodontitis was diagnosed by using the criteria of the Classification of Periodontal and Peri-Implant Diseases and Conditions 2017. Stage II of periodontitis was diagnosed in the presence of 3 to 4 mm interdental CAL at the site of greatest loss, 4 to maximum 5 mm PPD, the radiographic bone loss at the root coronal third, and no tooth loss due to periodontitis. Stage III was diagnosed in the presence of ≥5 mm interdental CAL, the radiographic bone loss extending to the middle or apical third of the root, ≤4 teeth loss due to periodontitis. In all cases, periodontitis had a generalized pattern (>30% of teeth involved) and grade B as patterns of the progression, based on indirect evidence (radiographic bone loss expressed as a percentage of root length divided by the age of the subject was from 0.25 to 1.0).
Patients were grouped by stratified randomization into three groups: the SRP Group (patients received scaling and root planing as a full-mouth procedure, n=25); the Arg Group (patients received oral L-arginine aspartate (Yuria-Pharm, Ukraine) at a dose of 1 g t.i.d. for 10 days after SRP, n=25); and the Orn Group (patients received oral L-ornithine aspartate (Farmak, Ukraine) at a dose of 3 g t.i.d. for 15 days after SRP, n=25). We used arginine and ornithine according to instructions for these medicines available for use in Ukraine. During the study, all patients were on a stable diet, without changing their rations and regiments.
For all participants, gender and age were recorded, and periodontal parameters such as periodontal pocket depth (PPD), clinical attachment level (CAL) and bleeding on probing (BoP) measurements were taken from six periodontal sites on all teeth (except for the third molars) by a single calibrated examiner using a manual periodontal probe (dental explorer tool labeled 0106.DT06.CP10, Den Tag, Italy). PPD and CAL were measured to the nearest 1 mm.
All patients were clinically examined before treatment and after 1 month ± 5 days.
Collection of gingival tissue samples For the precise immunohistochemical study, the gingival biopsy of approximately 3x3 mm was excised under local anesthesia before treatment and 1 month later in 5 selected patients per group. Biopsies were obtained in the same time-points, from a single site displaying the deepest pocket around suitable dental and periodontal procedures. Removal of these tissue biopsies did not interfere with the initial treatment plan or influence upon the expected clinical outcomes. After collection, biopsies were fixed in a 4% formalin solution for 24 hr of fixation, dehydrated, and embedded in paraffin.
Immunohistochemistry and antibodies Paraffin sections, 2-3 μm in thickness were deparaffinized and dehydrated. Heat-induced epitope retrieval in citrate buffer, power of hydrogen (pH) 6, was performed by successive heating the slides in the microwave oven, then allowed to cool, rinsed with phosphate-buffered saline (PBS), incubated with blocked reagent, rinsed, and incubated with mouse monoclonal CD68 antibodies (1:30, clone PG-M1, Diagnostic BioSystems, The Hague, The Netherlands) or anti-CD163 (1:100, clone 10D6, Diagnostic BioSystems, The Hague, The Netherlands). Then sections were stained with the 2-steps Mouse/Rabbit PolyVue Plus™ HRP/DAB Detection System (Diagnostic BioSystems, The Hague, The Netherlands), and counterstained with Mayer's haemalaun. PBS was used as a negative control, the lymph node tissue - as a positive control.
Evaluation of immunohistochemical staining CD68+ and CD163+ macrophages (Mφs) were estimated by counting the number of the cells by light microscope ×400 in intensive infiltrative areas, 5 regions from each slice were selected, and all 5 counts were taken for statistics. We counted immunopositive Mφs in the areas of cell infiltration, since they are directly related to inflammation. The number of cells per 10 000 μm2 was calculated as immunopositive cell density. Photos were obtained using the light microscope Axio Lab.A1 (Carl Zeiss, Göttingen, Germany) (×400).
Statistical analysis Small sample size was justified by the expectation of a high effect size, unknown null distribution, and compensated with adequate power non parametric statistics. Precise sample size calculation was not performed.
Means of PPD and CAL were calculated for sites with PD>4mm (affected sites). Statistical analysis was performed using GraphPad Prism 5 software (GraphPad Software, San Diego, USA) by means of descriptive statistics, chi-square test, one-way ANOVA and nonparametric ANOVA tests for multiple comparisons: Friedman - for dependent variables, Kruskal-Wallis test - for independent variables, with post-hoc analyzing. For descriptive statistics of cells numbers, the percentile ranges were also used because of non-normal distributions. The CD68+/CD163+ ratio was assessed by inter-group t-tests comparisons and Spearman correlation checking. P values of <0.05 were considered statistically significant in all of the analyses.
- Conditions
- Periodontitis
- Being tested
- Scaling and root planing, Oral L-arginine aspartate administration, Oral L-ornithine aspartate administration
- Keywords
- L-arginine, L-ornithine, M1 M2 macrophages, macrophages-targeted therapy, periodontitis
- Medical subject headings
- Periodontitis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Scaling and root planingProcedure or surgery
Also called SRP
Conventional periodontal therapy, non-surgical periodontal therapy
Oral L-arginine aspartate administrationDrug
Also called Oral supplementation with Tivortin® Aspartate (Yuria-Pharm, Ukraine)
The use of L-arginine aspartate as adjuncts to local conservative treatment (scaling and root planing) of periodontitis to optimize treatment by modulating local macrophage subpopulations
Oral L-ornithine aspartate administrationDrug
Also called Oral supplementation with Larnamin (Farmak, Ukraine)
The use of L-ornithine aspartate as adjuncts to local conservative treatment (scaling and root planing) of periodontitis to optimize treatment by modulating local macrophage subpopulations
| Study group | Role | What they receive |
|---|---|---|
| the SRP Group | Active comparator | Patients received conventional periodontal therapy including scaling and root planing as a full-mouth procedure, n=25. Receives: Procedure: Scaling and root planing |
| the Arg Group | Experimental | Patients received oral L-arginine aspartate (Yuria-Pharm, Ukraine) at a dose of 1 g t.i.d. for 10 days after conventional periodontal therapy, n=25. Receives: Procedure: Scaling and root planing; Drug: Oral L-arginine aspartate administration |
| the Orn Group | Experimental | Patients received oral L-ornithine aspartate (Farmak, Ukraine) at a dose of 3 g t.i.d. for 15 days after conventional periodontal therapy, n=25. Receives: Procedure: Scaling and root planing; Drug: Oral L-ornithine aspartate administration |
What is being measured
The primary outcome is the main question the study is designed to answer.
Periodontal pocket depth (PPD)
Mean changes in probing depth (PD). Measurements were taken from six periodontal sites on all teeth (except for the third molars) by a single calibrated examiner using a manual periodontal probe (0106.DT06.CP10, Den Tag, Italy) to the nearest 1 mm.
Measured: Before treatment and after 1 month ± 5 days.
Clinical attachment level (CAL)
Mean changes in clinical attachment level.Measurements were taken from six periodontal sites on all teeth (except for the third molars) by a single calibrated examiner using a manual periodontal probe (0106.DT06.CP10, Den Tag, Italy) to the nearest 1 mm.
Measured: Before treatment and after 1 month ± 5 days.
Bleeding on probing (BoP) measurements
Mean changes in BoP
Measured: Before treatment and after 1 month ± 5 days.
Secondary outcomes (1)
CD68+ and CD163+ macrophages density in gingiva
The number of cells per 10 000 μm2 was calculated as immunopositive cell density
Measured: Before treatment and after 1 month ± 5 days.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Sep 2021
- Study start20 Oct 2017
- Primary completion2 Oct 2018
- Study completion1 Nov 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (21)Papers the sponsor has linked to this study.
- Other trials for PeriodontitisStudies of the same condition, open and under way.
- 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Patients were grouped by stratified randomization into three groups: the SRP Group (patients received conventional periodontal therapy including scaling and root planing as a full-mouth procedure, n=25); the Arg Group (patients received oral L-arginine aspartate (Yuria-Pharm, Ukraine) at a dose of 1 g t.i.d. for 10 days after conventional periodontal therapy, n=25); and the Orn Group (patients received oral L-ornithine aspartate (Farmak, Ukraine) at a dose of 3 g t.i.d. for 15 days after conventional periodontal therapy, n=25).
- Masking
- None (open label)
- Enrolment
- 75 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ukrainian Medical Stomatological Academy
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Igor Kaydashev, Ukrainian Medical Stomatological Academy
- Investigators
- Igor P Kaydashev, Dr.hab., Principal investigator, Ukrainian Medical Stomatological Academy
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05042024
- Sponsor's protocol ID
- 0120U101151
- Status last verified
- Sep 2021
- First submitted
- 31 Aug 2021
- Last updated
- 17 Sep 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Because all the necessary participant data will be provided in the publication about the study
Publications
Papapanou 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 Clin Periodontol. 2018 Jun;45 Suppl 20:S162-S170. doi: 10.1111/jcpe.12946.
PubMed 29926490Shinkevich VI, Kaidashev IP. [The role of immune cells factors in the remodeling of gingiva at chronic generalized periodontal disease]. Stomatologiia (Mosk). 2012;91(1):23-7. Russian.
PubMed 22678603Zhou LN, Bi CS, Gao LN, An Y, Chen F, Chen FM. Macrophage polarization in human gingival tissue in response to periodontal disease. Oral Dis. 2019 Jan;25(1):265-273. doi: 10.1111/odi.12983. Epub 2018 Oct 12.
PubMed 30285304Shynkevych VI, Kaidashev IP. Contribution of macrophage subpopulations to the pathogenesis of chronic periodontitis in humans and perspectives for study. Review of the literature. Zaporozhye medical journal. 2019;21(1): 137-143. doi:10.14739/2310-1210.2019.1.155863.
Garaicoa-Pazmino C, Fretwurst T, Squarize CH, Berglundh T, Giannobile WV, Larsson L, Castilho RM. Characterization of macrophage polarization in periodontal disease. J Clin Periodontol. 2019 Aug;46(8):830-839. doi: 10.1111/jcpe.13156. Epub 2019 Jun 25.
PubMed 31152604Allam JP, Duan Y, Heinemann F, Winter J, Gotz W, Deschner J, Wenghoefer M, Bieber T, Jepsen S, Novak N. IL-23-producing CD68(+) macrophage-like cells predominate within an IL-17-polarized infiltrate in chronic periodontitis lesions. J Clin Periodontol. 2011 Oct;38(10):879-86. doi: 10.1111/j.1600-051X.2011.01752.x. Epub 2011 Aug 31.
PubMed 21883359Slots J. Periodontitis: facts, fallacies and the future. Periodontol 2000. 2017 Oct;75(1):7-23. doi: 10.1111/prd.12221.
PubMed 28758294Almubarak A, Tanagala KKK, Papapanou PN, Lalla E, Momen-Heravi F. Disruption of Monocyte and Macrophage Homeostasis in Periodontitis. Front Immunol. 2020 Feb 26;11:330. doi: 10.3389/fimmu.2020.00330. eCollection 2020.
PubMed 32210958Gordon S, Pluddemann A, Martinez Estrada F. Macrophage heterogeneity in tissues: phenotypic diversity and functions. Immunol Rev. 2014 Nov;262(1):36-55. doi: 10.1111/imr.12223.
PubMed 25319326Satoh T. [Functional diversity of disorder-specific macrophages]. Rinsho Ketsueki. 2018;59(6):805-811. doi: 10.11406/rinketsu.59.805. Japanese.
PubMed 29973463Kedia-Mehta N, Finlay DK. Competition for nutrients and its role in controlling immune responses. Nat Commun. 2019 May 9;10(1):2123. doi: 10.1038/s41467-019-10015-4.
PubMed 31073180Angajala A, Lim S, Phillips JB, Kim JH, Yates C, You Z, Tan M. Diverse Roles of Mitochondria in Immune Responses: Novel Insights Into Immuno-Metabolism. Front Immunol. 2018 Jul 12;9:1605. doi: 10.3389/fimmu.2018.01605. eCollection 2018.
PubMed 30050539Rath M, Muller I, Kropf P, Closs EI, Munder M. Metabolism via Arginase or Nitric Oxide Synthase: Two Competing Arginine Pathways in Macrophages. Front Immunol. 2014 Oct 27;5:532. doi: 10.3389/fimmu.2014.00532. eCollection 2014.
PubMed 25386178Nouwen LV, Everts B. Pathogens MenTORing Macrophages and Dendritic Cells: Manipulation of mTOR and Cellular Metabolism to Promote Immune Escape. Cells. 2020 Jan 9;9(1):161. doi: 10.3390/cells9010161.
PubMed 31936570Hardbower DM, Asim M, Luis PB, Singh K, Barry DP, Yang C, Steeves MA, Cleveland JL, Schneider C, Piazuelo MB, Gobert AP, Wilson KT. Ornithine decarboxylase regulates M1 macrophage activation and mucosal inflammation via histone modifications. Proc Natl Acad Sci U S A. 2017 Jan 31;114(5):E751-E760. doi: 10.1073/pnas.1614958114. Epub 2017 Jan 17.
PubMed 28096401
Study at a glance
From the registry record, last updated by the sponsor on 17 Sep 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Supplementation With L-ornithine Increases Representation Density of CD68+ and CD163+ Macrophages in Human Periodontitis Gingiva and Can Modulate Macrophages Phenotypes. Randomized Controlled Pilot Trial
- ClinicalTrials.gov ID
- NCT05042024
- Acronym / sponsor ID
- 0120U101151
- Conditions
- Periodontitis
- Keywords
- L-arginine, L-ornithine, M1 M2 macrophages, macrophages-targeted therapy, periodontitis
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 75 participants (actual)
- Lead sponsor
- Ukrainian Medical Stomatological AcademyUniversity, hospital or other
- Study start
- 20 Oct 2017 (actual)
- Primary completion
- 2 Oct 2018 (actual)
- Study completion
- 1 Nov 2018 (actual)
- First posted
- 13 Sep 2021 (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.
The aim of the study was to investigate whether oral administration of L-arginine or L-ornithine could modulate local representation density and ratio of macrophages in periodontitis-affected gingiva by using immunohistochemical detection of CD68+ and CD163+ macrophages in biopsies of the gingiva.
The null hypothesis tested was that L-arginine and L-ornithine have no influences on CD68+ and CD163+ macrophages densities when supplementing the treatment of periodontitis.
Materials and methods. 75 individuals with a diagnosis of generalized periodontitis at stages II-III and grade B (38 women and 37 men, 51% and 49%, respectively) were included in the study. Periodontitis was diagnosed by using the criteria of the Classification of Periodontal and Peri-Implant Diseases and Conditions 2017. 25 patients received scaling and root planing only; 25 patients additionally received L-arginine, and 25 - L-ornithine, according to instructions available in Ukraine.
For the immunohistochemical study of paraffin-embedded sections, the gingival biopsy was taken from 5 selected patients per group before treatment and after 1 month. CD68+ (cluster of differentiation 68 positive) and CD163+ cells served as a morphological equivalent of M1, M2 macrophages subpopulations, and their densities were calculated per 10000 μm2. Statistical analysis was performed by adequate power methods.
Detailed description
Study design The present work was the original research study. 75 individuals with a diagnosis of generalized periodontitis at stages II-III and grade B (38 women and 37 men, 51% and 49%, respectively) were included in the study. Periodontitis was diagnosed by using the criteria of the Classification of Periodontal and Peri-Implant Diseases and Conditions 2017. Stage II of periodontitis was diagnosed in the presence of 3 to 4 mm interdental CAL at the site of greatest loss, 4 to maximum 5 mm PPD, the radiographic bone loss at the root coronal third, and no tooth loss due to periodontitis. Stage III was diagnosed in the presence of ≥5 mm interdental CAL, the radiographic bone loss extending to the middle or apical third of the root, ≤4 teeth loss due to periodontitis. In all cases, periodontitis had a generalized pattern (>30% of teeth involved) and grade B as patterns of the progression, based on indirect evidence (radiographic bone loss expressed as a percentage of root length divided by the age of the subject was from 0.25 to 1.0).
Patients were grouped by stratified randomization into three groups: the SRP Group (patients received scaling and root planing as a full-mouth procedure, n=25); the Arg Group (patients received oral L-arginine aspartate (Yuria-Pharm, Ukraine) at a dose of 1 g t.i.d. for 10 days after SRP, n=25); and the Orn Group (patients received oral L-ornithine aspartate (Farmak, Ukraine) at a dose of 3 g t.i.d. for 15 days after SRP, n=25). We used arginine and ornithine according to instructions for these medicines available for use in Ukraine. During the study, all patients were on a stable diet, without changing their rations and regiments.
For all participants, gender and age were recorded, and periodontal parameters such as periodontal pocket depth (PPD), clinical attachment level (CAL) and bleeding on probing (BoP) measurements were taken from six periodontal sites on all teeth (except for the third molars) by a single calibrated examiner using a manual periodontal probe (dental explorer tool labeled 0106.DT06.CP10, Den Tag, Italy). PPD and CAL were measured to the nearest 1 mm.
All patients were clinically examined before treatment and after 1 month ± 5 days.
Collection of gingival tissue samples For the precise immunohistochemical study, the gingival biopsy of approximately 3x3 mm was excised under local anesthesia before treatment and 1 month later in 5 selected patients per group. Biopsies were obtained in the same time-points, from a single site displaying the deepest pocket around suitable dental and periodontal procedures. Removal of these tissue biopsies did not interfere with the initial treatment plan or influence upon the expected clinical outcomes. After collection, biopsies were fixed in a 4% formalin solution for 24 hr of fixation, dehydrated, and embedded in paraffin.
Immunohistochemistry and antibodies Paraffin sections, 2-3 μm in thickness were deparaffinized and dehydrated. Heat-induced epitope retrieval in citrate buffer, power of hydrogen (pH) 6, was performed by successive heating the slides in the microwave oven, then allowed to cool, rinsed with phosphate-buffered saline (PBS), incubated with blocked reagent, rinsed, and incubated with mouse monoclonal CD68 antibodies (1:30, clone PG-M1, Diagnostic BioSystems, The Hague, The Netherlands) or anti-CD163 (1:100, clone 10D6, Diagnostic BioSystems, The Hague, The Netherlands). Then sections were stained with the 2-steps Mouse/Rabbit PolyVue Plus™ HRP/DAB Detection System (Diagnostic BioSystems, The Hague, The Netherlands), and counterstained with Mayer's haemalaun. PBS was used as a negative control, the lymph node tissue - as a positive control.
Evaluation of immunohistochemical staining CD68+ and CD163+ macrophages (Mφs) were estimated by counting the number of the cells by light microscope ×400 in intensive infiltrative areas, 5 regions from each slice were selected, and all 5 counts were taken for statistics. We counted immunopositive Mφs in the areas of cell infiltration, since they are directly related to inflammation. The number of cells per 10 000 μm2 was calculated as immunopositive cell density. Photos were obtained using the light microscope Axio Lab.A1 (Carl Zeiss, Göttingen, Germany) (×400).
Statistical analysis Small sample size was justified by the expectation of a high effect size, unknown null distribution, and compensated with adequate power non parametric statistics. Precise sample size calculation was not performed.
Means of PPD and CAL were calculated for sites with PD>4mm (affected sites). Statistical analysis was performed using GraphPad Prism 5 software (GraphPad Software, San Diego, USA) by means of descriptive statistics, chi-square test, one-way ANOVA and nonparametric ANOVA tests for multiple comparisons: Friedman - for dependent variables, Kruskal-Wallis test - for independent variables, with post-hoc analyzing. For descriptive statistics of cells numbers, the percentile ranges were also used because of non-normal distributions. The CD68+/CD163+ ratio was assessed by inter-group t-tests comparisons and Spearman correlation checking. P values of <0.05 were considered statistically significant in all of the analyses.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- Patients were grouped by stratified randomization into three groups: the SRP Group (patients received conventional periodontal therapy including scaling and root planing as a full-mouth procedure, n=25); the Arg Group (patients received oral L-arginine aspartate (Yuria-Pharm, Ukraine) at a dose of 1 g t.i.d. for 10 days after conventional periodontal therapy, n=25); and the Orn Group (patients received oral L-ornithine aspartate (Farmak, Ukraine) at a dose of 3 g t.i.d. for 15 days after conventional periodontal therapy, n=25).
| Arm | Type | Receives |
|---|---|---|
| the SRP Group | Active comparator | Procedure: Scaling and root planingPatients received conventional periodontal therapy including scaling and root planing as a full-mouth procedure, n=25. |
| the Arg Group | Experimental | Procedure: Scaling and root planing, Drug: Oral L-arginine aspartate administrationPatients received oral L-arginine aspartate (Yuria-Pharm, Ukraine) at a dose of 1 g t.i.d. for 10 days after conventional periodontal therapy, n=25. |
| the Orn Group | Experimental | Procedure: Scaling and root planing, Drug: Oral L-ornithine aspartate administrationPatients received oral L-ornithine aspartate (Farmak, Ukraine) at a dose of 3 g t.i.d. for 15 days after conventional periodontal therapy, n=25. |
Who may qualify
- Ages
- 25 to 54 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- Presence of periodontitis
- Good general health
- At least 19 remaining teeth
- Written informed consent forms
Key exclusion criteria (6 listed)
- Antibiotics or anti-inflammatory medications use within the preceding 3 months
- Periodontal therapy within the previous 6 months
- Purulent exudation from periodontal pockets
- Pregnancy and breastfeeding
- Presence of severe, uncontrolled (decompensated) diseases of the internal organs, or neuropsychiatric disorders
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 |
|---|---|---|
| Scaling and root planingAlso: SRPConventional periodontal therapy, non-surgical periodontal therapy | Procedure or surgery | the Arg Group, the Orn Group, the SRP Group |
| Oral L-arginine aspartate administrationAlso: Oral supplementation with Tivortin® Aspartate (Yuria-Pharm, Ukraine)The use of L-arginine aspartate as adjuncts to local conservative treatment (scaling and root planing) of periodontitis to optimize treatment by modulating local macrophage subpopulations | Drug | the Arg Group |
| Oral L-ornithine aspartate administrationAlso: Oral supplementation with Larnamin (Farmak, Ukraine)The use of L-ornithine aspartate as adjuncts to local conservative treatment (scaling and root planing) of periodontitis to optimize treatment by modulating local macrophage subpopulations | Drug | the Orn Group |
Primary outcome
Periodontal pocket depth (PPD)
Time frame: Before treatment and after 1 month ± 5 days.
Mean changes in probing depth (PD). Measurements were taken from six periodontal sites on all teeth (except for the third molars) by a single calibrated examiner using a manual periodontal probe (0106.DT06.CP10, Den Tag, Italy) to the nearest 1 mm.
Clinical attachment level (CAL)
Time frame: Before treatment and after 1 month ± 5 days.
Mean changes in clinical attachment level.Measurements were taken from six periodontal sites on all teeth (except for the third molars) by a single calibrated examiner using a manual periodontal probe (0106.DT06.CP10, Den Tag, Italy) to the nearest 1 mm.
Bleeding on probing (BoP) measurements
Time frame: Before treatment and after 1 month ± 5 days.
Mean changes in BoP
1 secondary outcome
CD68+ and CD163+ macrophages density in gingiva
Time frame: Before treatment and after 1 month ± 5 days.
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 17 Sep 2021.
- Background: PubMed 29926490Papapanou 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 Clin Periodontol. 2018 Jun;45 Suppl 20:S162-S170. doi: 10.1111/jcpe.12946.
- Background: PubMed 22678603Shinkevich VI, Kaidashev IP. [The role of immune cells factors in the remodeling of gingiva at chronic generalized periodontal disease]. Stomatologiia (Mosk). 2012;91(1):23-7. Russian.
- Background: PubMed 30285304Zhou LN, Bi CS, Gao LN, An Y, Chen F, Chen FM. Macrophage polarization in human gingival tissue in response to periodontal disease. Oral Dis. 2019 Jan;25(1):265-273. doi: 10.1111/odi.12983. Epub 2018 Oct 12.
- BackgroundShynkevych VI, Kaidashev IP. Contribution of macrophage subpopulations to the pathogenesis of chronic periodontitis in humans and perspectives for study. Review of the literature. Zaporozhye medical journal. 2019;21(1): 137-143. doi:10.14739/2310-1210.2019.1.155863.
- Background: PubMed 31152604Garaicoa-Pazmino C, Fretwurst T, Squarize CH, Berglundh T, Giannobile WV, Larsson L, Castilho RM. Characterization of macrophage polarization in periodontal disease. J Clin Periodontol. 2019 Aug;46(8):830-839. doi: 10.1111/jcpe.13156. Epub 2019 Jun 25.
- Background: PubMed 21883359Allam JP, Duan Y, Heinemann F, Winter J, Gotz W, Deschner J, Wenghoefer M, Bieber T, Jepsen S, Novak N. IL-23-producing CD68(+) macrophage-like cells predominate within an IL-17-polarized infiltrate in chronic periodontitis lesions. J Clin Periodontol. 2011 Oct;38(10):879-86. doi: 10.1111/j.1600-051X.2011.01752.x. Epub 2011 Aug 31.
- Background: PubMed 28758294Slots J. Periodontitis: facts, fallacies and the future. Periodontol 2000. 2017 Oct;75(1):7-23. doi: 10.1111/prd.12221.
- Background: PubMed 32210958Almubarak A, Tanagala KKK, Papapanou PN, Lalla E, Momen-Heravi F. Disruption of Monocyte and Macrophage Homeostasis in Periodontitis. Front Immunol. 2020 Feb 26;11:330. doi: 10.3389/fimmu.2020.00330. eCollection 2020.
- Background: PubMed 25319326Gordon S, Pluddemann A, Martinez Estrada F. Macrophage heterogeneity in tissues: phenotypic diversity and functions. Immunol Rev. 2014 Nov;262(1):36-55. doi: 10.1111/imr.12223.
- Background: PubMed 29973463Satoh T. [Functional diversity of disorder-specific macrophages]. Rinsho Ketsueki. 2018;59(6):805-811. doi: 10.11406/rinketsu.59.805. Japanese.
- Background: PubMed 31073180Kedia-Mehta N, Finlay DK. Competition for nutrients and its role in controlling immune responses. Nat Commun. 2019 May 9;10(1):2123. doi: 10.1038/s41467-019-10015-4.
- Background: PubMed 30050539Angajala A, Lim S, Phillips JB, Kim JH, Yates C, You Z, Tan M. Diverse Roles of Mitochondria in Immune Responses: Novel Insights Into Immuno-Metabolism. Front Immunol. 2018 Jul 12;9:1605. doi: 10.3389/fimmu.2018.01605. eCollection 2018.
- Individual participant dataSharing planned: No. Because all the necessary participant data will be provided in the publication about the study
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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.
Igor P Kaydashev, Dr.hab. principal investigator
Ukrainian Medical Stomatological Academy
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Scaling and root planing, Oral L-arginine aspartate administration and Oral L-ornithine aspartate administration in people with Periodontitis, run by Ukrainian Medical Stomatological Academy at 1 site in Ukraine.
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 4 inclusion and 6 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 17 Sep 2021. 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 Ukraine. 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.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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?
Periodontal pocket depth (PPD) (time frame: Before treatment and after 1 month ± 5 days.). The study lists 3 primary outcomes in all. 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 NCT05042024, which also lists 21 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 17 Sep 2021.