Pulp Disease, DentalNCT06398327
Efficacy Of Proinflammatory Cytokines in The Primary Molar Pulpotomy
A study testing PULPOTOMY TREATMENT in people with Pulp Disease, Dental, run by Ataturk University at 1 site in Turkey (Türkiye).
Trial summary
One of the main goals of pediatric dentistry is to preserve the functions and structures of primary teeth until the time of exfoliation. Especially carious lesions are the main factor in the early loss of primary teeth. Read more about this study
- Who is it for?
- Ages 4 to 9 yearsHealthy volunteers can take part
- Conditions the study is for
- Pulp Disease, Dental
- What is being tested?
- PULPOTOMY TREATMENT
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 75 participants
- Where
- 1 siteTurkey (Türkiye)
- Study dates
- 5 Nov 2021to 17 May 2023
- 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 4 to 9 years
- All sexes
- Healthy volunteers accepted
- Child
Who may be able to join
- Healthy children between the ages of 6-9
- Children who do not have any systemic disease
- Primary second premolars in which physiological root resorption has not started.
- Cases where tooth decay at the interfaces exceeds ½ of the dentin thickness.
- Primary second premolars with provoked pain
- 4. Lack of percussion sensitivity 5. Absence of radiolucent image in the periapical and furcal areas on x-ray 6. Clinical absence of abscess and fistula
Who cannot join
- Children with systemic diseases
- Having percussion sensitivity
- Radiolucent appearance in the periapical and furcal areas on x-ray
- Clinical presence of fistula
- Having night pain
Trial locations and contacts
1 site in 1 country.
Turkey (Türkiye)1 site
Ataturk University Faculty of Dentistry
Yakutiye, Erzurum, 25240
About this study
Official title: Efficacy Of Proinflammatory Cytokines in the Clinical And Radiographic Outcomes of Different Primary Molar Pulpotomy Agents: A Comparative Study Featuring A Novel Biomarker For Pulpal Diagnosis
One of the main goals of pediatric dentistry is to preserve the functions and structures of primary teeth until the time of exfoliation. Especially carious lesions are the main factor in the early loss of primary teeth. Today, primary teeth can be kept in the mouth by applying different treatments depending on the degree of inflammation caused by carious lesions in the pulp tissue.Coronal pulpotomy application in asymptomatic primary teeth with deep carious lesions near the pulp is one of the most common methods to achieve the goal of retaining the tooth in place. The purpose of the pulpotomy technique is to remove the affected pulp tissue and maintain the normal function of the unaffected root pulp tissue until the tooth is naturally ready to exfoliate.
Studies have shown that the degree of pulp inflammation and the materials used are effective in the success of this treatment. In studies evaluating pulpal inflammation, many biomarkers have been shown to play significant roles at different levels of inflammation. Recently, Presepsin has been studied as a biomarker for detecting bacterial infections. However, there is no study in the literature on the use of Presepsin as a biomarker in endodontic treatments. In our study, it is thought that Presepsin biomarker could be detected in cases of acute or chronic infection in pulp tissue and could be considered as one of the mediators of pulpal inflammation.
Based on this, the aim of our study is to investigate whether the materials used in covering the pulp or the level of inflammation in the remaining pulp tissue is more important for the success of pulpotomy treatment. The inflammation level in the remaining pulp tissue will be measured using IL-6, IL-8, and Presepsin. Then, the one-year success of treatment in different groups where pulp tissue is randomly covered with MTA, NeoMTA, Biodentine, and Zinc oxide eugenol will be demonstrated. Thus, it will be evaluated whether materials previously found to be quite successful in other studies achieve success in pulps with high inflammation levels.
Read the detailed description
Tooth decay is a commonly encountered chronic infectious disease in children. Coronary pulpotomy treatment is generally preferred for teeth with deep decay lesions that are clinically and radiographically asymptomatic. The success of this treatment method is highly dependent on the inflammatory status of the pulp and the materials used. In predicting the clinical success of pulpotomy treatment, the severity of pulp inflammation must also be evaluated. A molecular approach that aids in the clinical distinction between reversible and irreversible pulpitis can increase the success rate of vital pulp therapy by accurately assessing the inflammation status of the pulp. Although various mediators' increases in advanced pulpal inflammation have been examined in many previous studies, the role of many biomolecules involved in pulpal inflammation has not yet been determined. Due to the complex nature of inflammatory pulp disease, it is unlikely that a small number of mediators would provide sufficient information to diagnose advanced inflammatory disease. Therefore, studies aimed at identifying new mediators remain relevant in dentistry. Presepsin, discovered in 2004, is a biomarker with high sensitivity and specificity that is highly important in the early diagnosis of bacterial diseases in medicine. When dental literature is reviewed, it is observed that presepsin has not been evaluated for the detection of bacterial inflammation in the pulp, and it is believed that this biomarker could be used for the early detection of pulpal inflammation. Thus, with the ability to measure presepsin levels using patient kits, pulpal inflammation can be quantitatively evaluated, aiding in the provision of accurate pulp treatments.The aim of our research is to investigate whether presepsin, a new biomarker that can be rapidly detected in bacterial infections, can also be used as a mediator in the detection of pulpal infections, and to evaluate the levels of the reliable markers of pulpal inflammation, IL-8 and IL-6, comparing the effect of these mediators on the success of treatment with the most successful materials used in pulpotomy treatment, MTA, Neo MTA, Biodentine and Zinc oxide eugenol.
This study was conducted in accordance with the Ataturk University Faculty of Medicine Ethics Committee approval (Date: 05.2021/ Session no:04/ Decision no:66) and guidelines of the Helsinki Declaration. Also the parents of child patients were comprehensively briefed about the procedures before the treatment and their written consents were obtained. Initially, a total of 75 children aged 4-9 years old (36 girls and 39 boys) with no systemic disease and presenting at least one primary second molar indicated for pulpotomy were included in the study and 4 pulpotomy agents (MTA, Biodentine™, NeoMTA™ and ZOE) were randomly divided into four study groups of 30 teeth and pulpotomy was applied to a total of 120 teeth.
In order to randomly distribute the study groups, Research Randomizer (Version 4.0) computer software from http://www.randomizer.org/ was used to generate a list before starting pulpotomy and pulpotomy agents were used accordingly.
Protocols for Treatment and Sample Storage:
For a better visibility a rubber-dam is placed over the tooth requiring pulpotomy following local anesthesia. Endodontic cavity was accessed by first removing the carious tissue, unroofing the pulp chamber with diamond round bur (no:18), removing the coronal tissue using a sterile tungsten carbide round bur (no:14) mounted low-speed contra-angled handpiece and clearing the remaining pulpal tissue with an excavator.
Before managing the pulpal hemorrhage, a sterile cotton pellet was placed over the pulp tissue for 30-45 sec. in order to obtain pulpal blood samples and specimens were collected into heparin coated tubes (Vacutainer, BD,USA) with 1mg saline solution and they were stored at -20 oC (-4.0°F) for 6 months until the day of testing.
Then pulpal hemostasis was achieved by placing 0.5 % NaOCl over the canal orifices for 30 sec. Primary molars, in which pulpal hemorrhage was controlled were randomly assigned to 4 different study groups (ProRoot MTA, Biodentine™, NeoMTA™, and ZOE respectively) and they were treated with pulpotomy. Glass ionomer cement was applied over all pulpotomy medications used in the study and pulpotomized teeth were restored with stainless steel crowns (SSCs).
Thawing Process and Assessment:
Samples were thawed at room temperature and centrifuged at 4000 rpm for 15 min. Then cotton pellets were removed from the test tubes and levels of presepsin, IL-6 and IL-8 were measured using enzyme-linked immunoassay (ELISA) [Human presepsin ELISA kit (Cat.No:E3754Hu, BT LAB,China),Human IL-6 ELISA Kit (Cat.No:E0090Hu,BT LAB,China), Human IL-8 ELISA Kit (Cat.No:E0089Hu, BT LAB,China)] test in accordance with the manufacturer's instructions. Kit measurement ranges for presepsin, IL-6 and IL-8 were 5-1000ng/L, 2-600ng/L and 5-1000ng/L respectively. The inter- assay CV were <10% for all biomarkers.
Clinical \& Radiographic Assessment Method:
Primary second molars were assessed clinically and radiographically at the post- treatment 6th and 12th months.
Spontaneous or stimulated pain, swellings in vestibular sulcus, fistula, pathological mobility, sensitivity to percussion and palpation, regional lymphadenopathy adjacent to the pulpotomized teeth were clinically assessed and presence of any of these symptoms were regarded as failed pulpotomy.
Radiolucency in the periapical or furcation areas, internal and external root resorptions, calcified root canals, widened periodontal ligament were radiographically evaluated and presence of any of these symptoms were also regarded as failure.
Additionally, presence of lesions in periapical or furcation areas in radiographs were also accepted as failure and these teeth underwent root canal treatment or extraction. Furthermore, teeth with internal root resorption were regarded as radiographically failed and they were just followed-up until any symptom occurred.
Statistical Analysis Descriptive statistics (count, ratio, mean, standard deviation, minimum and maximum variables) were used to summarize the set of data in the present study. Fisher's exact test was employed to analyze the relationship between pre-treatment clinical findings and dental pathologies developed at the post-treatment 12th month when pathologies became more apparent. Relationship between the mean levels of pulpal inflammatory biomarkers and dental pathologies occurred at the post-treatment 12th month was analyzed using Mann-Whitney U test. Mann-Whitney U test was also used to compare the mean levels of inflammatory biomarkers and clinical findings. Kruskal Wallis test was used to compare the differences between the mean scores of inflammatory biomarkers by the pulpotomy agents used.
Threshold values were calculated with Receiver Operating Characteristics (ROC) analysis and then these obtained values were used to determine the highest biomarker scores in the pulpotomy material groups. All study analysis were performed with IBM® SPSS® Statistics 25 at a significance level of 0.05.
- Conditions
- Pulp Disease, Dental
- Being tested
- PULPOTOMY TREATMENT
- Keywords
- Presepsin, MTA, Neo MTA, Biodentine, zinc oxide eugenol, ıl-6, IL-8, Pulpal inflammation, Pulpotomy treatment, Primary molar teeth
- Medical subject headings
- Dental Pulp Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PULPOTOMY TREATMENTProcedure or surgery
During pulpotomy treatment, a bleeding sample was taken from the pulp and levels of presepsin, IL-6 and IL-8, which are important inflammation markers, were determined. During the treatment, MTA, Neo MTA, Biodentine and ZOE groups were randomly selected and the remaining pulp tissue was covered. After pulpotomy treatment, the teeth were followed for one year. Treatment success was evaluated according to the material used in teeth with high levels of inflammation at the beginning.
| Study group | Role | What they receive |
|---|---|---|
| Zinc oxide eugenol cement | Active comparator | During pulpotomy treatment, a blood sample was taken from the coronal pulp and stored. The remaining pulp tissue was covered with ZOE, randomly selected from among four material groups. The teeth treated with ZOE were monitored for 12 months. Subsequently, the levels of IL-6, IL-8, and Presepsin in the blood were measured using the ELISA method and noted in ng/ml. Thus, the effect of the material used on the success of the treatment was determined based on the level of pulpal inflammation before treatment. Receives: Procedure: PULPOTOMY TREATMENT |
| Mineral Trioxide Aggregate (MTA) | Active comparator | During pulpotomy treatment, a blood sample was taken from the coronal pulp and stored. The remaining pulp tissue was covered with MTA, randomly selected from among four material groups. The teeth treated with MTA were monitored for 12 months. Subsequently, the levels of IL-6, IL-8, and Presepsin in the blood were measured using the ELISA method and noted in ng/ml. Thus, the effect of the material used on the success of the treatment was determined based on the level of pulpal inflammation before treatment. Receives: Procedure: PULPOTOMY TREATMENT |
| NeoMTA (newly developed mta) | Active comparator | During pulpotomy treatment, a blood sample was taken from the coronal pulp and stored. The remaining pulp tissue was covered with NeoMTA, randomly selected from among four material groups. The teeth treated with NeoMTA were monitored for 12 months. Subsequently, the levels of IL-6, IL-8, and Presepsin in the blood were measured using the ELISA method and noted in ng/ml. Thus, the effect of the material used on the success of the treatment was determined based on the level of pulpal inflammation before treatment. Receives: Procedure: PULPOTOMY TREATMENT |
| Biodentine (biomaterial) | Active comparator | During pulpotomy treatment, a blood sample was taken from the coronal pulp and stored. The remaining pulp tissue was covered with Biodentine, randomly selected from among four material groups. The teeth treated with Biodentine were monitored for 12 months. Subsequently, the levels of IL-6, IL-8, and Presepsin in the blood were measured using the ELISA method and noted in ng/ml. Thus, the effect of the material used on the success of the treatment was determined based on the level of pulpal inflammation before treatment. Receives: Procedure: PULPOTOMY TREATMENT |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinical Success After Pulpotomy Treatment
No signs of abscess or any swelling related to the tooth, no signs of fistula or other pathology, no signs of pathologic mobility, no post-operative pain, no pain on palpation or percussion of the tooth.
Measured: 6 Month - 1 Year
Radiographic Success After Pulpotomy Treatment
No signs of root resorption (internal or external), no signs of furcation involvement or periapical radiolucency, no signs of loss of lamina dura, presence of normal appearance of periodontal ligament space.
Measured: 6 Month - 1 Year
IL-6 amount measurement using ELISA kit
IL-6 levels were measured in ng/ml using the ELISA method. The measurement procedure was followed according to the manufacturer's instructions. The anti-IL-6 polyclonal antibody was pre-coated on 96-well plates. Blood samples and a biotin-conjugated antibody were added to the wells supplemented with Avidin-Biotin-Peroxidase Complex and 3,3',5,5'-tetramethylbenzidine in a mildly acidic buffer. A blue-colored product was produced and turned to yellow after an acidic stop solution was added. The intensity of the color yellow was proportional to the IL-6 amount bound on the plate. The optical density absorbance was measured spectrophotometrically at 450nm in a microplate reader and the concentration of IL-6 was calculated. For the expression of IL-6 concentrations in the samples, a standard curve was used.Optimal threshold values (cut-offs) for biomarkers were determined based on sensitivity and specificity, which were calculated from a ROC curve.
Measured: 6 Month - 1 Year
IL-8 amount measurement using ELISA kit
IL-8 levels were measured in ng/ml using the ELISA method. The measurement procedure was followed according to the manufacturer's instructions. The anti-IL-8 polyclonal antibody was pre-coated on 96-well plates. Blood samples and a biotin-conjugated antibody were added to the wells supplemented with Avidin-Biotin-Peroxidase Complex and 3,3',5,5'-tetramethylbenzidine in a mildly acidic buffer. A blue-colored product was produced and turned to yellow after an acidic stop solution was added. The intensity of the color yellow was proportional to the IL-8 amount bound on the plate. The optical density absorbance was measured spectrophotometrically at 450nm in a microplate reader and the concentration of IL-8 was calculated. For the expression of IL-8 concentrations in the samples, a standard curve was used.Optimal threshold values (cut-offs) for biomarkers were determined based on sensitivity and specificity, which were calculated from a ROC curve.
Measured: 6 Month - 1 Year
Presepsin amount measurement using ELISA kit
Presepsin levels were measured in ng/ml using the ELISA method. The measurement procedure was followed according to the manufacturer's instructions. The anti-Presepsin polyclonal antibody was pre-coated on 96-well plates. Blood samples and a biotin-conjugated antibody were added to the wells supplemented with Avidin-Biotin-Peroxidase Complex and 3,3',5,5'-tetramethylbenzidine in a mildly acidic buffer. A blue-colored product was produced and turned to yellow after an acidic stop solution was added. The intensity of the color yellow was proportional to the Presepsin amount bound on the plate. The optical density absorbance was measured spectrophotometrically at 450nm in a microplate reader and the concentration of Presepsin was calculated. For the expression of Presepsin concentrations in the samples, a standard curve was used.Optimal threshold values (cut-offs) for biomarkers were determined based on sensitivity and specificity, which were calculated from a ROC curve.
Measured: 6 Month - 1 Year
Secondary outcomes (3)
The Correlation Between Pre-Treatment Pain Presence and Radiographic Success After Pulpotomy Treatment
The success of treatment was evaluated radiographically after 12 months in teeth with pain related to pre-treatment stimuli.At the end of 12 months; Teeth with no signs of root resorption (internal or external), furcation involvement or periapical radiolucency, no signs of lamina dura loss, and a normal appearance of the periodontal ligament were considered radiographically successful.
Measured: 1 Year
The Correlation Between The Severity of Pulp Bleeding During Treatment and Radiographic Success After Pulpotomy Treatment
The radiographic success of pulpotomy treatment was evaluated at 12 months in teeth with severe pulp bleeding during treatment.At the end of 12 months; Teeth with no signs of root resorption (internal or external), furcation involvement or periapical radiolucency, no signs of lamina dura loss, and a normal appearance of the periodontal ligament were considered radiographically successful.
Measured: 1 Year
The Correlation Between Pulp Bleeding Time During Treatment and Radiographic Success After Pulpotomy Treatment
The radiographic success of pulpotomy treatment was evaluated at the 12th month, depending on the shorter (less than 3 minutes) and longer (3-5 minutes) bleeding duration during treatment.At the end of 12 months; Teeth with no signs of root resorption (internal or external), furcation involvement or periapical radiolucency, no signs of lamina dura loss, and a normal appearance of the periodontal ligament were considered radiographically successful.
Measured: 1 Year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 May 2024
- Study start5 Nov 2021
- Primary completion5 Nov 2022
- Study completion17 May 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (28)Papers the sponsor has linked to this study.
- Other trials for Pulp Disease, DentalStudies of the same condition, open and under way.
- More trials run by Ataturk 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
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 75 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ataturk University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, AYBİKE BAŞ, Ataturk University
- Investigators
- AYBİKE BAŞ, Principal investigator, Ataturk University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06398327
- Sponsor's protocol ID
- B.30.2.ATA.0.01.00/345
- Status last verified
- Apr 2024
- First submitted
- 7 Apr 2024
- Last updated
- 3 May 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Ahuja S, Surabhi K, Gandhi K, Kapoor R, Malhotra R, Kumar D. Comparative Evaluation of Success of Biodentine and Mineral Trioxide Aggregate with Formocresol as Pulpotomy Medicaments in Primary Molars: An In Vivo Study. Int J Clin Pediatr Dent. 2020 Mar-Apr;13(2):167-173. doi: 10.5005/jp-journals-10005-1740.
PubMed 32742096Alsanouni M, Bawazir OA. A Randomized Clinical Trial of NeoMTA Plus in Primary Molar Pulpotomies. Pediatr Dent. 2019 Mar 15;41(2):107-111.
PubMed 30992107Bani M, Aktas N, Cinar C, Odabas ME. The Clinical and Radiographic Success of Primary Molar Pulpotomy Using Biodentine and Mineral Trioxide Aggregate: A 24-Month Randomized Clinical Trial. Pediatr Dent. 2017 Jul 15;39(4):284-288.
PubMed 29122067Bossu M, Iaculli F, Di Giorgio G, Salucci A, Polimeni A, Di Carlo S. Different Pulp Dressing Materials for the Pulpotomy of Primary Teeth: A Systematic Review of the Literature. J Clin Med. 2020 Mar 19;9(3):838. doi: 10.3390/jcm9030838.
PubMed 32204501Cordell S, Kratunova E, Marion I, Alrayyes S, Alapati SB. A Randomized Controlled Trial Comparing the Success of Mineral Trioxide Aggregate and Ferric Sulfate as Pulpotomy Medicaments for Primary Molars. J Dent Child (Chic). 2021 May 15;88(2):120-128.
PubMed 34321144Cuadros-Fernandez C, Lorente Rodriguez AI, Saez-Martinez S, Garcia-Binimelis J, About I, Mercade M. Short-term treatment outcome of pulpotomies in primary molars using mineral trioxide aggregate and Biodentine: a randomized clinical trial. Clin Oral Investig. 2016 Sep;20(7):1639-45. doi: 10.1007/s00784-015-1656-4. Epub 2015 Nov 18.
PubMed 26578117Donnermeyer D, Dammaschke T, Lipski M, Schafer E. Effectiveness of diagnosing pulpitis: A systematic review. Int Endod J. 2023 Oct;56 Suppl 3:296-325. doi: 10.1111/iej.13762. Epub 2022 May 25.
PubMed 35536159Elsalhy M, Azizieh F, Raghupathy R. Cytokines as diagnostic markers of pulpal inflammation. Int Endod J. 2013 Jun;46(6):573-80. doi: 10.1111/iej.12030. Epub 2012 Dec 13.
PubMed 23240887Farges JC, Keller JF, Carrouel F, Durand SH, Romeas A, Bleicher F, Lebecque S, Staquet MJ. Odontoblasts in the dental pulp immune response. J Exp Zool B Mol Dev Evol. 2009 Jul 15;312B(5):425-36. doi: 10.1002/jez.b.21259.
PubMed 19067439Gonzalez-Lara A, Ruiz-Rodriguez MS, Pierdant-Perez M, Garrocho-Rangel JA, Pozos-Guillen AJ. Zinc Oxide-Eugenol Pulpotomy in Primary Teeth: A 24-Month Follow-up. J Clin Pediatr Dent. 2016;40(2):107-12. doi: 10.17796/1053-4628-40.2.107.
PubMed 26950810Gopinath VK, Anwar K. Histological evaluation of pulp tissue from second primary molars correlated with clinical and radiographic caries findings. Dent Res J (Isfahan). 2014 Mar;11(2):199-203.
PubMed 24932190Guo J, Zhang N, Cheng Y. Comparative efficacy of medicaments or techniques for pulpotomy of primary molars: a network meta-analysis. Clin Oral Investig. 2023 Jan;27(1):91-104. doi: 10.1007/s00784-022-04830-1. Epub 2022 Dec 29.
PubMed 36580161Hirsch V, Wolgin M, Mitronin AV, Kielbassa AM. Inflammatory cytokines in normal and irreversibly inflamed pulps: A systematic review. Arch Oral Biol. 2017 Oct;82:38-46. doi: 10.1016/j.archoralbio.2017.05.008. Epub 2017 Jun 1.
PubMed 28600966Juneja P, Kulkarni S. Clinical and radiographic comparison of biodentine, mineral trioxide aggregate and formocresol as pulpotomy agents in primary molars. Eur Arch Paediatr Dent. 2017 Aug;18(4):271-278. doi: 10.1007/s40368-017-0299-3. Epub 2017 Aug 5.
PubMed 28780718Matsuo T, Nakanishi T, Shimizu H, Ebisu S. A clinical study of direct pulp capping applied to carious-exposed pulps. J Endod. 1996 Oct;22(10):551-6. doi: 10.1016/S0099-2399(96)80017-3.
PubMed 9198445
Study at a glance
From the registry record, last updated by the sponsor on 3 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy Of Proinflammatory Cytokines in the Clinical And Radiographic Outcomes of Different Primary Molar Pulpotomy Agents: A Comparative Study Featuring A Novel Biomarker For Pulpal Diagnosis
- ClinicalTrials.gov ID
- NCT06398327
- Acronym / sponsor ID
- B.30.2.ATA.0.01.00/345
- Conditions
- Pulp Disease, Dental
- Keywords
- Presepsin, MTA, Neo MTA, Biodentine, zinc oxide eugenol, ıl-6, IL-8, Pulpal inflammation
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 75 participants (actual)
- Lead sponsor
- Ataturk UniversityUniversity, hospital or other
- Study start
- 5 Nov 2021 (actual)
- Primary completion
- 5 Nov 2022 (actual)
- Study completion
- 17 May 2023 (actual)
- First posted
- 3 May 2024 (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.
One of the main goals of pediatric dentistry is to preserve the functions and structures of primary teeth until the time of exfoliation. Especially carious lesions are the main factor in the early loss of primary teeth. Today, primary teeth can be kept in the mouth by applying different treatments depending on the degree of inflammation caused by carious lesions in the pulp tissue.Coronal pulpotomy application in asymptomatic primary teeth with deep carious lesions near the pulp is one of the most common methods to achieve the goal of retaining the tooth in place. The purpose of the pulpotomy technique is to remove the affected pulp tissue and maintain the normal function of the unaffected root pulp tissue until the tooth is naturally ready to exfoliate.
Studies have shown that the degree of pulp inflammation and the materials used are effective in the success of this treatment. In studies evaluating pulpal inflammation, many biomarkers have been shown to play significant roles at different levels of inflammation. Recently, Presepsin has been studied as a biomarker for detecting bacterial infections. However, there is no study in the literature on the use of Presepsin as a biomarker in endodontic treatments. In our study, it is thought that Presepsin biomarker could be detected in cases of acute or chronic infection in pulp tissue and could be considered as one of the mediators of pulpal inflammation.
Based on this, the aim of our study is to investigate whether the materials used in covering the pulp or the level of inflammation in the remaining pulp tissue is more important for the success of pulpotomy treatment. The inflammation level in the remaining pulp tissue will be measured using IL-6, IL-8, and Presepsin. Then, the one-year success of treatment in different groups where pulp tissue is randomly covered with MTA, NeoMTA, Biodentine, and Zinc oxide eugenol will be demonstrated. Thus, it will be evaluated whether materials previously found to be quite successful in other studies achieve success in pulps with high inflammation levels.
Detailed description
Tooth decay is a commonly encountered chronic infectious disease in children. Coronary pulpotomy treatment is generally preferred for teeth with deep decay lesions that are clinically and radiographically asymptomatic. The success of this treatment method is highly dependent on the inflammatory status of the pulp and the materials used. In predicting the clinical success of pulpotomy treatment, the severity of pulp inflammation must also be evaluated. A molecular approach that aids in the clinical distinction between reversible and irreversible pulpitis can increase the success rate of vital pulp therapy by accurately assessing the inflammation status of the pulp. Although various mediators' increases in advanced pulpal inflammation have been examined in many previous studies, the role of many biomolecules involved in pulpal inflammation has not yet been determined. Due to the complex nature of inflammatory pulp disease, it is unlikely that a small number of mediators would provide sufficient information to diagnose advanced inflammatory disease. Therefore, studies aimed at identifying new mediators remain relevant in dentistry. Presepsin, discovered in 2004, is a biomarker with high sensitivity and specificity that is highly important in the early diagnosis of bacterial diseases in medicine. When dental literature is reviewed, it is observed that presepsin has not been evaluated for the detection of bacterial inflammation in the pulp, and it is believed that this biomarker could be used for the early detection of pulpal inflammation. Thus, with the ability to measure presepsin levels using patient kits, pulpal inflammation can be quantitatively evaluated, aiding in the provision of accurate pulp treatments.The aim of our research is to investigate whether presepsin, a new biomarker that can be rapidly detected in bacterial infections, can also be used as a mediator in the detection of pulpal infections, and to evaluate the levels of the reliable markers of pulpal inflammation, IL-8 and IL-6, comparing the effect of these mediators on the success of treatment with the most successful materials used in pulpotomy treatment, MTA, Neo MTA, Biodentine and Zinc oxide eugenol.
This study was conducted in accordance with the Ataturk University Faculty of Medicine Ethics Committee approval (Date: 05.2021/ Session no:04/ Decision no:66) and guidelines of the Helsinki Declaration. Also the parents of child patients were comprehensively briefed about the procedures before the treatment and their written consents were obtained. Initially, a total of 75 children aged 4-9 years old (36 girls and 39 boys) with no systemic disease and presenting at least one primary second molar indicated for pulpotomy were included in the study and 4 pulpotomy agents (MTA, Biodentine™, NeoMTA™ and ZOE) were randomly divided into four study groups of 30 teeth and pulpotomy was applied to a total of 120 teeth.
In order to randomly distribute the study groups, Research Randomizer (Version 4.0) computer software from http://www.randomizer.org/ was used to generate a list before starting pulpotomy and pulpotomy agents were used accordingly.
Protocols for Treatment and Sample Storage:
For a better visibility a rubber-dam is placed over the tooth requiring pulpotomy following local anesthesia. Endodontic cavity was accessed by first removing the carious tissue, unroofing the pulp chamber with diamond round bur (no:18), removing the coronal tissue using a sterile tungsten carbide round bur (no:14) mounted low-speed contra-angled handpiece and clearing the remaining pulpal tissue with an excavator.
Before managing the pulpal hemorrhage, a sterile cotton pellet was placed over the pulp tissue for 30-45 sec. in order to obtain pulpal blood samples and specimens were collected into heparin coated tubes (Vacutainer, BD,USA) with 1mg saline solution and they were stored at -20 oC (-4.0°F) for 6 months until the day of testing.
Then pulpal hemostasis was achieved by placing 0.5 % NaOCl over the canal orifices for 30 sec. Primary molars, in which pulpal hemorrhage was controlled were randomly assigned to 4 different study groups (ProRoot MTA, Biodentine™, NeoMTA™, and ZOE respectively) and they were treated with pulpotomy. Glass ionomer cement was applied over all pulpotomy medications used in the study and pulpotomized teeth were restored with stainless steel crowns (SSCs).
Thawing Process and Assessment:
Samples were thawed at room temperature and centrifuged at 4000 rpm for 15 min. Then cotton pellets were removed from the test tubes and levels of presepsin, IL-6 and IL-8 were measured using enzyme-linked immunoassay (ELISA) [Human presepsin ELISA kit (Cat.No:E3754Hu, BT LAB,China),Human IL-6 ELISA Kit (Cat.No:E0090Hu,BT LAB,China), Human IL-8 ELISA Kit (Cat.No:E0089Hu, BT LAB,China)] test in accordance with the manufacturer's instructions. Kit measurement ranges for presepsin, IL-6 and IL-8 were 5-1000ng/L, 2-600ng/L and 5-1000ng/L respectively. The inter- assay CV were <10% for all biomarkers.
Clinical \& Radiographic Assessment Method:
Primary second molars were assessed clinically and radiographically at the post- treatment 6th and 12th months.
Spontaneous or stimulated pain, swellings in vestibular sulcus, fistula, pathological mobility, sensitivity to percussion and palpation, regional lymphadenopathy adjacent to the pulpotomized teeth were clinically assessed and presence of any of these symptoms were regarded as failed pulpotomy.
Radiolucency in the periapical or furcation areas, internal and external root resorptions, calcified root canals, widened periodontal ligament were radiographically evaluated and presence of any of these symptoms were also regarded as failure.
Additionally, presence of lesions in periapical or furcation areas in radiographs were also accepted as failure and these teeth underwent root canal treatment or extraction. Furthermore, teeth with internal root resorption were regarded as radiographically failed and they were just followed-up until any symptom occurred.
Statistical Analysis Descriptive statistics (count, ratio, mean, standard deviation, minimum and maximum variables) were used to summarize the set of data in the present study. Fisher's exact test was employed to analyze the relationship between pre-treatment clinical findings and dental pathologies developed at the post-treatment 12th month when pathologies became more apparent. Relationship between the mean levels of pulpal inflammatory biomarkers and dental pathologies occurred at the post-treatment 12th month was analyzed using Mann-Whitney U test. Mann-Whitney U test was also used to compare the mean levels of inflammatory biomarkers and clinical findings. Kruskal Wallis test was used to compare the differences between the mean scores of inflammatory biomarkers by the pulpotomy agents used.
Threshold values were calculated with Receiver Operating Characteristics (ROC) analysis and then these obtained values were used to determine the highest biomarker scores in the pulpotomy material groups. All study analysis were performed with IBM® SPSS® Statistics 25 at a significance level of 0.05.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Zinc oxide eugenol cement | Active comparator | Procedure: PULPOTOMY TREATMENTDuring pulpotomy treatment, a blood sample was taken from the coronal pulp and stored. The remaining pulp tissue was covered with ZOE, randomly selected from among four material groups. The teeth treated with ZOE were monitored for 12 months. Subsequently, the levels of IL-6, IL-8, and Presepsin in the blood were measured using the ELISA method and noted in ng/ml. Thus, the effect of the material used on the success of the treatment was determined based on the level of pulpal inflammation before treatment. |
| Mineral Trioxide Aggregate (MTA) | Active comparator | Procedure: PULPOTOMY TREATMENTDuring pulpotomy treatment, a blood sample was taken from the coronal pulp and stored. The remaining pulp tissue was covered with MTA, randomly selected from among four material groups. The teeth treated with MTA were monitored for 12 months. Subsequently, the levels of IL-6, IL-8, and Presepsin in the blood were measured using the ELISA method and noted in ng/ml. Thus, the effect of the material used on the success of the treatment was determined based on the level of pulpal inflammation before treatment. |
| NeoMTA (newly developed mta) | Active comparator | Procedure: PULPOTOMY TREATMENTDuring pulpotomy treatment, a blood sample was taken from the coronal pulp and stored. The remaining pulp tissue was covered with NeoMTA, randomly selected from among four material groups. The teeth treated with NeoMTA were monitored for 12 months. Subsequently, the levels of IL-6, IL-8, and Presepsin in the blood were measured using the ELISA method and noted in ng/ml. Thus, the effect of the material used on the success of the treatment was determined based on the level of pulpal inflammation before treatment. |
| Biodentine (biomaterial) | Active comparator | Procedure: PULPOTOMY TREATMENTDuring pulpotomy treatment, a blood sample was taken from the coronal pulp and stored. The remaining pulp tissue was covered with Biodentine, randomly selected from among four material groups. The teeth treated with Biodentine were monitored for 12 months. Subsequently, the levels of IL-6, IL-8, and Presepsin in the blood were measured using the ELISA method and noted in ng/ml. Thus, the effect of the material used on the success of the treatment was determined based on the level of pulpal inflammation before treatment. |
Who may qualify
- Ages
- 4 to 9 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
Key inclusion criteria (6 listed)
- Healthy children between the ages of 6-9
- Children who do not have any systemic disease
- Primary second premolars in which physiological root resorption has not started.
- Cases where tooth decay at the interfaces exceeds ½ of the dentin thickness.
- Primary second premolars with provoked pain
Key exclusion criteria (5 listed)
- Children with systemic diseases
- Having percussion sensitivity
- Radiolucent appearance in the periapical and furcal areas on x-ray
- Clinical presence of fistula
- Having night pain
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 |
|---|---|---|
| PULPOTOMY TREATMENTDuring pulpotomy treatment, a bleeding sample was taken from the pulp and levels of presepsin, IL-6 and IL-8, which are important inflammation markers, were determined. During the treatment, MTA, Neo MTA, Biodentine and ZOE groups were randomly selected and the remaining pulp tissue was covered. After pulpotomy treatment, the teeth were followed for one year. Treatment success was evaluated according to the material used in teeth with high levels of inflammation at the beginning. | Procedure or surgery | Biodentine (biomaterial), Mineral Trioxide Aggregate (MTA), NeoMTA (newly developed mta), Zinc oxide eugenol cement |
Primary outcome
Clinical Success After Pulpotomy Treatment
Time frame: 6 Month - 1 Year
No signs of abscess or any swelling related to the tooth, no signs of fistula or other pathology, no signs of pathologic mobility, no post-operative pain, no pain on palpation or percussion of the tooth.
Radiographic Success After Pulpotomy Treatment
Time frame: 6 Month - 1 Year
No signs of root resorption (internal or external), no signs of furcation involvement or periapical radiolucency, no signs of loss of lamina dura, presence of normal appearance of periodontal ligament space.
IL-6 amount measurement using ELISA kit
Time frame: 6 Month - 1 Year
IL-6 levels were measured in ng/ml using the ELISA method. The measurement procedure was followed according to the manufacturer's instructions. The anti-IL-6 polyclonal antibody was pre-coated on 96-well plates. Blood samples and a biotin-conjugated antibody were added to the wells supplemented with Avidin-Biotin-Peroxidase Complex and 3,3',5,5'-tetramethylbenzidine in a mildly acidic buffer. A blue-colored product was produced and turned to yellow after an acidic stop solution was added. The intensity of the color yellow was proportional to the IL-6 amount bound on the plate. The optical density absorbance was measured spectrophotometrically at 450nm in a microplate reader and the concentration of IL-6 was calculated. For the expression of IL-6 concentrations in the samples, a standard curve was used.Optimal threshold values (cut-offs) for biomarkers were determined based on sensitivity and specificity, which were calculated from a ROC curve.
IL-8 amount measurement using ELISA kit
Time frame: 6 Month - 1 Year
IL-8 levels were measured in ng/ml using the ELISA method. The measurement procedure was followed according to the manufacturer's instructions. The anti-IL-8 polyclonal antibody was pre-coated on 96-well plates. Blood samples and a biotin-conjugated antibody were added to the wells supplemented with Avidin-Biotin-Peroxidase Complex and 3,3',5,5'-tetramethylbenzidine in a mildly acidic buffer. A blue-colored product was produced and turned to yellow after an acidic stop solution was added. The intensity of the color yellow was proportional to the IL-8 amount bound on the plate. The optical density absorbance was measured spectrophotometrically at 450nm in a microplate reader and the concentration of IL-8 was calculated. For the expression of IL-8 concentrations in the samples, a standard curve was used.Optimal threshold values (cut-offs) for biomarkers were determined based on sensitivity and specificity, which were calculated from a ROC curve.
Presepsin amount measurement using ELISA kit
Time frame: 6 Month - 1 Year
Presepsin levels were measured in ng/ml using the ELISA method. The measurement procedure was followed according to the manufacturer's instructions. The anti-Presepsin polyclonal antibody was pre-coated on 96-well plates. Blood samples and a biotin-conjugated antibody were added to the wells supplemented with Avidin-Biotin-Peroxidase Complex and 3,3',5,5'-tetramethylbenzidine in a mildly acidic buffer. A blue-colored product was produced and turned to yellow after an acidic stop solution was added. The intensity of the color yellow was proportional to the Presepsin amount bound on the plate. The optical density absorbance was measured spectrophotometrically at 450nm in a microplate reader and the concentration of Presepsin was calculated. For the expression of Presepsin concentrations in the samples, a standard curve was used.Optimal threshold values (cut-offs) for biomarkers were determined based on sensitivity and specificity, which were calculated from a ROC curve.
3 secondary outcomes
The Correlation Between Pre-Treatment Pain Presence and Radiographic Success After Pulpotomy Treatment
Time frame: 1 Year
The Correlation Between The Severity of Pulp Bleeding During Treatment and Radiographic Success After Pulpotomy Treatment
Time frame: 1 Year
The Correlation Between Pulp Bleeding Time During Treatment and Radiographic Success After Pulpotomy Treatment
Time frame: 1 Year
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 3 May 2024.
- Results publication: PubMed 32742096Ahuja S, Surabhi K, Gandhi K, Kapoor R, Malhotra R, Kumar D. Comparative Evaluation of Success of Biodentine and Mineral Trioxide Aggregate with Formocresol as Pulpotomy Medicaments in Primary Molars: An In Vivo Study. Int J Clin Pediatr Dent. 2020 Mar-Apr;13(2):167-173. doi: 10.5005/jp-journals-10005-1740.
- Results publication: PubMed 30992107Alsanouni M, Bawazir OA. A Randomized Clinical Trial of NeoMTA Plus in Primary Molar Pulpotomies. Pediatr Dent. 2019 Mar 15;41(2):107-111.
- Results publication: PubMed 29122067Bani M, Aktas N, Cinar C, Odabas ME. The Clinical and Radiographic Success of Primary Molar Pulpotomy Using Biodentine and Mineral Trioxide Aggregate: A 24-Month Randomized Clinical Trial. Pediatr Dent. 2017 Jul 15;39(4):284-288.
- Results publication: PubMed 32204501Bossu M, Iaculli F, Di Giorgio G, Salucci A, Polimeni A, Di Carlo S. Different Pulp Dressing Materials for the Pulpotomy of Primary Teeth: A Systematic Review of the Literature. J Clin Med. 2020 Mar 19;9(3):838. doi: 10.3390/jcm9030838.
- Results publication: PubMed 34321144Cordell S, Kratunova E, Marion I, Alrayyes S, Alapati SB. A Randomized Controlled Trial Comparing the Success of Mineral Trioxide Aggregate and Ferric Sulfate as Pulpotomy Medicaments for Primary Molars. J Dent Child (Chic). 2021 May 15;88(2):120-128.
- Results publication: PubMed 26578117Cuadros-Fernandez C, Lorente Rodriguez AI, Saez-Martinez S, Garcia-Binimelis J, About I, Mercade M. Short-term treatment outcome of pulpotomies in primary molars using mineral trioxide aggregate and Biodentine: a randomized clinical trial. Clin Oral Investig. 2016 Sep;20(7):1639-45. doi: 10.1007/s00784-015-1656-4. Epub 2015 Nov 18.
- Results publication: PubMed 35536159Donnermeyer D, Dammaschke T, Lipski M, Schafer E. Effectiveness of diagnosing pulpitis: A systematic review. Int Endod J. 2023 Oct;56 Suppl 3:296-325. doi: 10.1111/iej.13762. Epub 2022 May 25.
- Results publication: PubMed 23240887Elsalhy M, Azizieh F, Raghupathy R. Cytokines as diagnostic markers of pulpal inflammation. Int Endod J. 2013 Jun;46(6):573-80. doi: 10.1111/iej.12030. Epub 2012 Dec 13.
- Results publication: PubMed 19067439Farges JC, Keller JF, Carrouel F, Durand SH, Romeas A, Bleicher F, Lebecque S, Staquet MJ. Odontoblasts in the dental pulp immune response. J Exp Zool B Mol Dev Evol. 2009 Jul 15;312B(5):425-36. doi: 10.1002/jez.b.21259.
- Results publication: PubMed 26950810Gonzalez-Lara A, Ruiz-Rodriguez MS, Pierdant-Perez M, Garrocho-Rangel JA, Pozos-Guillen AJ. Zinc Oxide-Eugenol Pulpotomy in Primary Teeth: A 24-Month Follow-up. J Clin Pediatr Dent. 2016;40(2):107-12. doi: 10.17796/1053-4628-40.2.107.
- Results publication: PubMed 24932190Gopinath VK, Anwar K. Histological evaluation of pulp tissue from second primary molars correlated with clinical and radiographic caries findings. Dent Res J (Isfahan). 2014 Mar;11(2):199-203.
- Results publication: PubMed 36580161Guo J, Zhang N, Cheng Y. Comparative efficacy of medicaments or techniques for pulpotomy of primary molars: a network meta-analysis. Clin Oral Investig. 2023 Jan;27(1):91-104. doi: 10.1007/s00784-022-04830-1. Epub 2022 Dec 29.
- 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.
AYBİKE BAŞ principal investigator
Ataturk 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 PULPOTOMY TREATMENT in people with Pulp Disease, Dental, run by Ataturk 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 6 inclusion and 5 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 3 May 2024. 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?
Clinical Success After Pulpotomy Treatment (time frame: 6 Month - 1 Year). The study lists 5 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 NCT06398327, which also lists 28 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 3 May 2024.