Cell-free Autologous Regenerative Endodontics Treatment for Teeth With Periapical Lesions (CARETT)

Periapical Diseases Clinical Trial

— CARETT  

Official title:

Cell-free Autologous Regenerative Endodontics Treatment for Permanent Mature Teeth With Pulp Necrosis and Periapical Lesions: a Randomized, Controlled Phase III Clinical Trial (CARETT)

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05305417
• Other study ID #: 211
• Status: Not yet recruiting
• Phase: N/A
• Start date: March 2023
• Est. completion date: March 2025

Study information

• Verified date: March 2022
• Source: Universidad de Valparaiso
• Contact: Juan Caro, DDS
• Phone: +56975242484
• Email: juancarlos.caro[@]uv.cl
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Conventional endodontic treatment has been the treatment of choice for the management of signs and symptoms of mature permanent teeth with pulpal necrosis and periapical lesion with predictable and favorable results. However, treatment outcomes have not shown improvement or innovation in decades. The main objective of this study is to evaluate the clinical effectiveness of a regenerative endodontic procedure (cell-free and autologous protocol) versus conventional endodontics in the resolution of signs and symptoms of periapical lesion and pulp vitality-sensitivity in mature permanent teeth with a diagnosis of pulpal necrosis and periapical lesion.

Description:

Conventional endodontic treatment has been an effective treatment option for decades to treat signs and symptoms in mature permanent teeth with a diagnosis of apical lesion due to pulpal necrosis, allowing the teeth to be kept in the mouth free of signs/symptoms but devitalized. The clinical effectiveness of conventional treatment in this type of case is ≥80%, with some variations according to different studies. Despite advances and modifications in treatment protocols, this therapy has not shown improvements or innovations in its results in recent decades. The Regenerative Endodontics alternative is postulated as a biologically based endodontic treatment option that allows to resolve the signs and symptoms along with dental revitalization through the regeneration of the pulpal connective tissue, generating a substantive possibility of innovation and improvements to the therapy of conventional endodontics. Various regenerative endodontic protocols have been proposed to achieve pulp tissue regeneration, from sophisticated techniques that involve cell transplantation, provision of scaffolds and/or signaling molecules, or simpler protocols that appeal to the autologous capacity of the organism to regenerate tissue. lost. The main objective of this study is to evaluate the clinical effectiveness of a cell-free regenerative endodontic procedure with the contribution of an autologous scaffold (L-PRF) versus conventional endodontics in the recovery of signs of periapical lesion and pulp vitality-sensitivity in mature permanent teeth with diagnosis of pulpal necrosis and periapical lesion.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 228
• Est. completion date: March 2025
• Est. primary completion date: March 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

Inclusion Criteria:

• Male or female (18-60y) systemically healthy or chronic disease controlled
• Uniradicular or multiradicular permanent mature teeth
• Teeth with diagnosis of pulp necrosis (negative response to thermal-cold pulp test) and sings or symptoms (clinical-radiographic) of periapical lesion.
• Root anatomy with curvatures = 30°
• Feasibility of adhesive tooth restoration (direct or indirect)
• Voluntary participation under informed consent

Exclusion Criteria:

• Pregnant or lactating woman
• Signs of moderate or severe periodontal disease
• Teeth with signs of radicular fracture (vertical or horizontal), signs of root resorption (endo-exo)
• teeth with impossibility of good prognosis of coronary rehabilitation by direct or indirect adhesive technique
• Teeth that to treat can not to be correctly isolate with rubber dam

Related Conditions & MeSH terms

• Dental Pulp Necrosis
• Necrosis
• Periapical Diseases
• Pulp Necroses

Intervention

Procedure:
• Autologous Regenerative Endodontic Treatment
The intervention consist in achieve an access to the teeth root canal system, do a chemico-mechanical preparation each root canal for to be obturated with an autologous biological scaffold and bioactive biomaterials to maintain teeth free of signs/symptoms caused by pulp necroses and periapical lesions
• Conventional Root Canal Treatment
The intervention consist in achieve an access to the teeth root canal system, do a chemico-mechanical preparation each root canal for to be obturated with an inert biomaterial to maintain teeth free of signs/symptoms caused by pulp necroses and periapical lesions

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Universidad de Valparaiso

References & Publications (21)

About I. Proceedings of the Pulp Biology and Regeneration Group Symposium 2019: Bridging Basic and Translational Research in Pulp Biology-Developing Technologies for Regenerating Vital Dental Tissues. J Endod. 2020 Sep;46(9S):S1. doi: 10.1016/j.joen.2020.06.018. — View Citation

Arslan H, Ahmed HMA, Sahin Y, Doganay Yildiz E, Gündogdu EC, Güven Y, Khalilov R. Regenerative Endodontic Procedures in Necrotic Mature Teeth with Periapical Radiolucencies: A Preliminary Randomized Clinical Study. J Endod. 2019 Jul;45(7):863-872. doi: 10.1016/j.joen.2019.04.005. Epub 2019 May 31. — View Citation

Brizuela C, Meza G, Urrejola D, Quezada MA, Concha G, Ramírez V, Angelopoulos I, Cadiz MI, Tapia-Limonchi R, Khoury M. Cell-Based Regenerative Endodontics for Treatment of Periapical Lesions: A Randomized, Controlled Phase I/II Clinical Trial. J Dent Res. 2020 May;99(5):523-529. doi: 10.1177/0022034520913242. Epub 2020 Mar 23. — View Citation

Chrepa V, Henry MA, Daniel BJ, Diogenes A. Delivery of Apical Mesenchymal Stem Cells into Root Canals of Mature Teeth. J Dent Res. 2015 Dec;94(12):1653-9. doi: 10.1177/0022034515596527. Epub 2015 Jul 20. — View Citation

Diogenes A, Ruparel NB. Regenerative Endodontic Procedures: Clinical Outcomes. Dent Clin North Am. 2017 Jan;61(1):111-125. doi: 10.1016/j.cden.2016.08.004. Review. — View Citation

Ducret M, Fabre H, Celle A, Mallein-Gerin F, Perrier-Groult E, Alliot-Licht B, Farges JC. Current challenges in human tooth revitalization. Biomed Mater Eng. 2017;28(s1):S159-S168. doi: 10.3233/BME-171637. Review. — View Citation

Farzaneh M, Abitbol S, Lawrence HP, Friedman S; Toronto Study. Treatment outcome in endodontics-the Toronto Study. Phase II: initial treatment. J Endod. 2004 May;30(5):302-9. — View Citation

Friedman S, Abitbol S, Lawrence HP. Treatment outcome in endodontics: the Toronto Study. Phase 1: initial treatment. J Endod. 2003 Dec;29(12):787-93. — View Citation

Galler KM, Buchalla W, Hiller KA, Federlin M, Eidt A, Schiefersteiner M, Schmalz G. Influence of root canal disinfectants on growth factor release from dentin. J Endod. 2015 Mar;41(3):363-8. doi: 10.1016/j.joen.2014.11.021. Epub 2015 Jan 13. — View Citation

Galler KM, D'Souza RN, Federlin M, Cavender AC, Hartgerink JD, Hecker S, Schmalz G. Dentin conditioning codetermines cell fate in regenerative endodontics. J Endod. 2011 Nov;37(11):1536-41. doi: 10.1016/j.joen.2011.08.027. — View Citation

Galler KM. Clinical procedures for revitalization: current knowledge and considerations. Int Endod J. 2016 Oct;49(10):926-36. doi: 10.1111/iej.12606. Epub 2016 Feb 1. Review. — View Citation

Glynis A, Foschi F, Kefalou I, Koletsi D, Tzanetakis GN. Regenerative Endodontic Procedures for the Treatment of Necrotic Mature Teeth with Apical Periodontitis: A Systematic Review and Meta-analysis of Randomized Controlled Trials. J Endod. 2021 Jun;47(6):873-882. doi: 10.1016/j.joen.2021.03.015. Epub 2021 Mar 31. Review. — View Citation

He L, Kim SG, Gong Q, Zhong J, Wang S, Zhou X, Ye L, Ling J, Mao JJ. Regenerative Endodontics for Adult Patients. J Endod. 2017 Sep;43(9S):S57-S64. doi: 10.1016/j.joen.2017.06.012. — View Citation

Jha P, Virdi MS, Nain S. A Regenerative Approach for Root Canal Treatment of Mature Permanent Teeth: Comparative Evaluation with 18 Months Follow-up. Int J Clin Pediatr Dent. 2019 May-Jun;12(3):182-188. doi: 10.5005/jp-journals-10005-1616. — View Citation

Marquis VL, Dao T, Farzaneh M, Abitbol S, Friedman S. Treatment outcome in endodontics: the Toronto Study. Phase III: initial treatment. J Endod. 2006 Apr;32(4):299-306. — View Citation

Moazami F, Sahebi S, Sobhnamayan F, Alipour A. Success rate of nonsurgical endodontic treatment of nonvital teeth with variable periradicular lesions. Iran Endod J. 2011 Summer;6(3):119-24. Epub 2011 Aug 15. — View Citation

Ng YL, Mann V, Rahbaran S, Lewsey J, Gulabivala K. Outcome of primary root canal treatment: systematic review of the literature - part 1. Effects of study characteristics on probability of success. Int Endod J. 2007 Dec;40(12):921-39. Epub 2007 Oct 10. Review. — View Citation

Ng YL, Mann V, Rahbaran S, Lewsey J, Gulabivala K. Outcome of primary root canal treatment: systematic review of the literature -- Part 2. Influence of clinical factors. Int Endod J. 2008 Jan;41(1):6-31. Epub 2007 Oct 10. Review. — View Citation

Paredes-Vieyra J, Enriquez FJ. Success rate of single- versus two-visit root canal treatment of teeth with apical periodontitis: a randomized controlled trial. J Endod. 2012 Sep;38(9):1164-9. doi: 10.1016/j.joen.2012.05.021. Epub 2012 Jul 26. — View Citation

Smith AJ, Scheven BA, Takahashi Y, Ferracane JL, Shelton RM, Cooper PR. Dentine as a bioactive extracellular matrix. Arch Oral Biol. 2012 Feb;57(2):109-21. doi: 10.1016/j.archoralbio.2011.07.008. Review. — View Citation

Widbiller M, Eidt A, Lindner SR, Hiller KA, Schweikl H, Buchalla W, Galler KM. Dentine matrix proteins: isolation and effects on human pulp cells. Int Endod J. 2018 May;51 Suppl 4:e278-e290. doi: 10.1111/iej.12754. Epub 2017 Mar 14. — View Citation

* Note: There are 21 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Efficacy of therapy	Number of treated tooth that remain in mouth free of clinical (negative percussion, negative palpation, abscence of inflammation, pain and fistula) and radiographic (total or partial reduction on size of periapical lesion) signs or symptoms at 12 month post operatory.	12 month
Secondary	Tooth re-sensibilization	Number of treated tooth that response positively to thermal pulp sensibility test (cold stimulus) after 3, 6 and 12 months post operatory in relation with the initial negative pulp test. The positive-negative pulp sensibility response of treated teeth first is standardized testing the homologous vital tooth on the mouth.	3, 6 and 12 month
Secondary	Tooth re-vitalization	Number of treated tooth that response positively to Vitality Pulp Test Doppler laser flowmetry after 3, 6 and 12 month. This Vitality Test assess pulpal blood flow by the detection of light scatter generated by moving erythrocytes. The positive-negative pulp vitality response of the treated teeth first is standardized testing the homologous vital tooth on the mouth.	3, 6 and 12 month
Secondary	Periapical lesion resolution	Resolution of an periapical lesion using Periapical Index (PI), a scoring system for registration of apical periodontitis in radiographs	3, 6 and 12 month
Secondary	Procedure Time	total time required to perform each of the therapies recorded in minutes	intraoperatory