Regenerative Endodontics Using Different Intracanal Medicaments on Radiographic Outcomes and Periapical MMP-8 Levels

NCT ID: NCT05581706

Last Updated: 2023-12-27

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

23 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-09-01

Study Completion Date

2021-03-01

Brief Summary

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Two-session regenerative endodontic treatment was applied to 20 immature mandibular first molars with symptomatic irreversible pulpitis and symptomatic apical periodontitis. At the end of the first session, calcium hydroxide \[Ca(OH)2\] was applied to 10 randomly selected teeth and double antibiotic paste (DAP) intracanal medicaments were applied to the other 10 teeth. The effects of intracanal medicaments on periapical MMP-8 levels were determined by immunofluorometric assay (IFMA) in periapical tissue fluid samples taken from the distal root canal in the first and second sessions.

Detailed Description

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The aim of the study was to investigate the effects of two different intracanal medicaments used during regenerative endodontic treatment (RET) on periapical MMP-8 in relation to the radiological outcomes of RET. After local anesthesia and rubber dam isolation were provided, disinfection procedures were applied gently in accordance with the current RET protocol of American Association of Endodontics (AAE) on the molar teeth. Periapical tissue fluid samples were taken with paper points placed to protrude 2 mm from the distal root canal tip. Calcium hydroxide \[Ca(OH)2\] was placed in 10 randomly selected teeth and double antibiotic paste (DAP) intracanal medicaments were placed in the other 10 teeth. Fourteen days later in the second session, the final sampling procedure was performed as in the first session. Then, the treatment was completed according to the current RET protocol of AAE and permanent restorations were made. The success of the treatment and its effect on root development were evaluated by comparing the standard radiographs taken at the end of the treatment and 12 months follow up. MMP-8 levels were measured by immunofluorometric assay (IFMA) in the periapical tissue fluid samples. First and second session MMP-8 levels were compared according to the groups of medicaments \[Ca(OH)2 and DAP groups\] placed in the root canals.

Conditions

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Regenerative Endodontics

Keywords

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regenerative endodontics intracanal medicaments MMP-8

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Outcome Assessors

Study Groups

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Regenerative endodontic treatment with calcium hydroxide

Regenerative endodontic treatment (RET) performed with procedures of American Association of Endodontics (AAE) in two sessions. At the end of the first session, periapical tissue fluid samples (baseline samples) were collected.

Calcium hydroxide medicament was prepared by mixing with sterile distilled water and then placed in the coronal 1/3 of the root canals.

In the second session (14 days after first treatment), the medicaments in the root canals were carefully removed with 5 ml sterile distilled water irrigation. Periapical tissue fluid samples were obtained from the distal canal using the same protocol as described previously (final samples). Then RET was finished according to the treatment protocol of AAE.

Group Type ACTIVE_COMPARATOR

Place the freshly prepared calcium hydroxide in to the root canals

Intervention Type COMBINATION_PRODUCT

Calcium hydroxide (Merck, Darmstadt, Germany): prepared by mixing with sterile distilled water and then placed in the coronal 1/3 of the root canals.

Regenerative endodontic treatment with double antibiotic paste

Regenerative endodontic treatment (RET) performed with procedures of American Association of Endodontics (AAE) in two sessions. At the end of the first session, periapical tissue fluid samples (baseline samples) were collected.

Double antibiotic paste (DAP) was prepared by mixing same amount of metronidazole and ciprofloxacin powdered antibiotics (1:1) and combined with sterile distilled water to form an ointment. DAP was introduced in roots canals using a lentulo to fill the entire root canal space.

In the second session (14 days after first treatment) after removal of DAP in the root canals, periapical tissue fluid samples were obtained the same protocol as described previously (final samples). Then RET was finished according to the treatment protocol of AAE.

Group Type ACTIVE_COMPARATOR

Place the freshly prepared double antibiotic paste in to the root canals

Intervention Type COMBINATION_PRODUCT

Double antibiotic paste (DAP): metronidazole (Flagyl, Sanofi-Aventis, Turkey) and ciprofloxacin (Cipro, Biofarma, Turkey) powdered antibiotics were stored and sealed in airtight containers. The same amount of each drug powder (1:1) was mixed and the mixed samples were combined with sterile distilled water to form an ointment. DAP was introduced in roots canals using a lentulo to fill the entire root canal space.

Radiographic evaluation

Pre-operative, post-operative and final recall (12th months follow up) standart digital radiographs were taken from patients with film holder. The radiographs saved and transferred to Image J software (version 1.47, National Institutes of Health, Bethesda, MD). The standardized radiographs were further aligned using the TurboReg plugin (Biomedical Imaging Group, Swiss Federal Institute of Technology, Lausanne, Switzerland) within the Image J toolkit to minimize any distortions caused by variability in the angulation.

All images were calibrated according to size #2 SPP (vertical dimension 31 mm, horizontal dimension 41 mm) using the ''set scale'' option in Image J. Thereafter, the root lengths, root width and radiographic root area were measured on both preoperative and final recall images to evaluate treatment outcomes.

Group Type ACTIVE_COMPARATOR

Taking standart periapical radiography with film holder

Intervention Type DIAGNOSTIC_TEST

Post-operative periapical radiographs were obtained with Digora Optime SPP system (Soredex Corp., Tuusula, Finland) using intraoral film holders to keep the plates parallel to the long axis of the teeth. A size #2 SPP was used for all exposures. SPPs were exposed with a Gendex Oralix DC dental x-ray unit (Gendex Dental Systems, Milan, Italy) operating at 60 kVp, 7 mA, 0.25 sec. and the plates were scanned immediately after exposure. The clinical and radiographical follow up was performed on 12th months.

Image-J program (version 1.47, National Institutes of Health, Bethesda, MD) with TurboReg plug-in (Biomedical Imaging Group, Swiss Federal Institute of Technology, Lausanne, Switzerland) was used to determine the increase in root length, root width, and radiographic root area at 12th month follow up.

Periapical tissue exudate sample collection and Immunofluorometric assay MMP-8

At the end of the first session, periapical tissue fluid samples (baseline samples) were collected by introducing 3 sterile #45 paper points into the root canal until 2 mm passing through the root apex from the distal canal. After waiting for 1 min, the paper points were withdrawn, the tip was cut from 4 mm and were transferred to sterile Eppendorf tubes. At the beginnign of the second session periapical tissue fluid samples were obtained from the distal canal using the same protocol as described in the first session (final samples).

Baseline and final MMP-8 concentrations were determined by a time-resolved immunofluorometric assay (IFMA). The monoclonal MMP-8 specific antibodies 8708 and 8706 (Oy Medix Biochemica Ab, Espoo, Finland) were used as a catching antibody and a tracer antibody, respectively. The tracer antibody was labeled using europium-chelate

Group Type ACTIVE_COMPARATOR

Sample collection for immunofluorometric assay

Intervention Type OTHER

Periapical exudate samples were collected at the beginning of the RET and at 14th day. MMP-8 levels were measured by immunofluorometric assay (IFMA). Briefly, two monoclonal MMP-8-specific antibodies, 8708 and 8706 (Oy Medix Biochemica Ab, Espoo, Finland) were used as catching antibody and tracer antibody, respectively. Samples were diluted in enzyme buffer (50 mM Tris-HCl, pH 7.5; 0.2 mM NaCl, 1 mM CaCl2). Twenty microlitres of samples and 80 μl of assay buffer (20 mM Tris-HCl, pH 7.5, 0.5 M NaCl, 5 mM CaCl2, 0.5% BSA, 0.05% sodium azide and 20 mg/l diethylenetriaminepentaacetic acid with 2 μg/ml normal mouse serum) were pipetted into the wells. The tracer antibody was labelled using europium chelate. After adding the enhancement solution, fluorescence was measured using a 1234 Delfia Research Fluorometer (Wallac, Turku, Finland).

Interventions

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Place the freshly prepared calcium hydroxide in to the root canals

Calcium hydroxide (Merck, Darmstadt, Germany): prepared by mixing with sterile distilled water and then placed in the coronal 1/3 of the root canals.

Intervention Type COMBINATION_PRODUCT

Place the freshly prepared double antibiotic paste in to the root canals

Double antibiotic paste (DAP): metronidazole (Flagyl, Sanofi-Aventis, Turkey) and ciprofloxacin (Cipro, Biofarma, Turkey) powdered antibiotics were stored and sealed in airtight containers. The same amount of each drug powder (1:1) was mixed and the mixed samples were combined with sterile distilled water to form an ointment. DAP was introduced in roots canals using a lentulo to fill the entire root canal space.

Intervention Type COMBINATION_PRODUCT

Taking standart periapical radiography with film holder

Post-operative periapical radiographs were obtained with Digora Optime SPP system (Soredex Corp., Tuusula, Finland) using intraoral film holders to keep the plates parallel to the long axis of the teeth. A size #2 SPP was used for all exposures. SPPs were exposed with a Gendex Oralix DC dental x-ray unit (Gendex Dental Systems, Milan, Italy) operating at 60 kVp, 7 mA, 0.25 sec. and the plates were scanned immediately after exposure. The clinical and radiographical follow up was performed on 12th months.

Image-J program (version 1.47, National Institutes of Health, Bethesda, MD) with TurboReg plug-in (Biomedical Imaging Group, Swiss Federal Institute of Technology, Lausanne, Switzerland) was used to determine the increase in root length, root width, and radiographic root area at 12th month follow up.

Intervention Type DIAGNOSTIC_TEST

Sample collection for immunofluorometric assay

Periapical exudate samples were collected at the beginning of the RET and at 14th day. MMP-8 levels were measured by immunofluorometric assay (IFMA). Briefly, two monoclonal MMP-8-specific antibodies, 8708 and 8706 (Oy Medix Biochemica Ab, Espoo, Finland) were used as catching antibody and tracer antibody, respectively. Samples were diluted in enzyme buffer (50 mM Tris-HCl, pH 7.5; 0.2 mM NaCl, 1 mM CaCl2). Twenty microlitres of samples and 80 μl of assay buffer (20 mM Tris-HCl, pH 7.5, 0.5 M NaCl, 5 mM CaCl2, 0.5% BSA, 0.05% sodium azide and 20 mg/l diethylenetriaminepentaacetic acid with 2 μg/ml normal mouse serum) were pipetted into the wells. The tracer antibody was labelled using europium chelate. After adding the enhancement solution, fluorescence was measured using a 1234 Delfia Research Fluorometer (Wallac, Turku, Finland).

Intervention Type OTHER

Other Intervention Names

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Ca(OH)2 medicament DAP medicament Determination of rooth lenght, rooth width, radiographic root area IFMA

Eligibility Criteria

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Inclusion Criteria

\- Healthy children with irreversible pulpitis with symptomatic apical periodontitis (SIP-SAP), indication for RET and informed consent from the patients.

Exclusion Criteria

* Children with extra oral swelling or luxation with a deep periodontal pocket and whom application of RET was contraindicated.
* The teeth were indicated for vital pulp therapy (assesed during treatment)
* Children who have used antibiotics in the past 3 months and are uncooperative during treatment
* Children who have used any painkillers during the treatment
Minimum Eligible Age

6 Years

Maximum Eligible Age

9 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Ege University

OTHER

Sponsor Role lead

Responsible Party

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Burç Pekpınarlı

Principal investigator, Asst. Dr

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Burç Pekpınarlı

Role: PRINCIPAL_INVESTIGATOR

Ege University Faculty of Dentistry

Locations

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Ege University Faculty of Dentistry Pediatric Dentistry

Izmir, , Turkey (Türkiye)

Site Status

Countries

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Turkey (Türkiye)

References

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Torabinejad M, Alexander A, Vahdati SA, Grandhi A, Baylink D, Shabahang S. Effect of Residual Dental Pulp Tissue on Regeneration of Dentin-pulp Complex: An In Vivo Investigation. J Endod. 2018 Dec;44(12):1796-1801. doi: 10.1016/j.joen.2018.09.005.

Reference Type BACKGROUND
PMID: 30477665 (View on PubMed)

Sabeti M, Golchert K, Torabinejad M. Regeneration of Pulp-Dentin Complex in a Tooth with Symptomatic Irreversible Pulpitis and Open Apex Using Regenerative Endodontic Procedures. J Endod. 2021 Feb;47(2):247-252. doi: 10.1016/j.joen.2020.09.021. Epub 2020 Oct 10.

Reference Type BACKGROUND
PMID: 33045267 (View on PubMed)

Wahlgren J, Salo T, Teronen O, Luoto H, Sorsa T, Tjaderhane L. Matrix metalloproteinase-8 (MMP-8) in pulpal and periapical inflammation and periapical root-canal exudates. Int Endod J. 2002 Nov;35(11):897-904. doi: 10.1046/j.1365-2591.2002.00587.x.

Reference Type BACKGROUND
PMID: 12453017 (View on PubMed)

Kuula H, Salo T, Pirila E, Tuomainen AM, Jauhiainen M, Uitto VJ, Tjaderhane L, Pussinen PJ, Sorsa T. Local and systemic responses in matrix metalloproteinase 8-deficient mice during Porphyromonas gingivalis-induced periodontitis. Infect Immun. 2009 Feb;77(2):850-9. doi: 10.1128/IAI.00873-08. Epub 2008 Nov 24.

Reference Type BACKGROUND
PMID: 19029300 (View on PubMed)

Bose R, Nummikoski P, Hargreaves K. A retrospective evaluation of radiographic outcomes in immature teeth with necrotic root canal systems treated with regenerative endodontic procedures. J Endod. 2009 Oct;35(10):1343-9. doi: 10.1016/j.joen.2009.06.021. Epub 2009 Aug 15.

Reference Type BACKGROUND
PMID: 19801227 (View on PubMed)

Reynaud af Geijersstam A, Sorsa T, Stackelberg S, Tervahartiala T, Haapasalo M. Effect of E. faecalis on the release of serine proteases elastase and cathepsin G, and collagenase-2 (MMP-8) by human polymorphonuclear leukocytes (PMNs). Int Endod J. 2005 Sep;38(9):667-77. doi: 10.1111/j.1365-2591.2005.01011.x.

Reference Type BACKGROUND
PMID: 16104981 (View on PubMed)

Martinho FC, Nascimento GG, Leite FR, Gomes AP, Freitas LF, Camoes IC. Clinical influence of different intracanal medications on Th1-type and Th2-type cytokine responses in apical periodontitis. J Endod. 2015 Feb;41(2):169-75. doi: 10.1016/j.joen.2014.09.028. Epub 2014 Nov 11.

Reference Type BACKGROUND
PMID: 25453567 (View on PubMed)

Pekpinarli B, Kaval ME, Cogulu D, Ilhan B, Sorsa T, Tervahartiala T, Oncag O. The effect of calcium hydroxide and double antibiotic paste on radiographic outcomes and periapical MMP-8 levels in regenerative endodontic procedures: a randomized clinical trial. J Appl Oral Sci. 2024 Sep 20;32:e20240122. doi: 10.1590/1678-7757-2024-0122. eCollection 2024.

Reference Type DERIVED
PMID: 39319904 (View on PubMed)

Other Identifiers

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Regenerative Endodontics

Identifier Type: -

Identifier Source: org_study_id