Encapsulated Mesenchymal Stem Cells for Dental Pulp Regeneration.

Study Overview
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Brief Summary
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To compare the dental survival in a period of one year of mature permanent teeth with apical lesion following the administration of encapsulated Mesenchymal Stem Cells under a regenerative endodontic procedure and a conventional root canal treatment.

Detailed Description
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This is a controlled clinical trial designed to evaluate the survival of mature permanent teeth with apical lesion treated with regenerative endodontic procedure (REP) based on encapsulated Mesenchymal Stem Cells in a biological scaffold. The REP will be compared to the conventional endodontic therapy. The REP is based on the use of umbilical cord-derived mesenchymal stem cells encapsulated in a plasma-derived biomaterial . The study group will use the disinfection protocol, indicated in the clinical considerations for regenerative procedures as recommended by the American Association of Endodontics, using a paste of calcium hydroxide prepared with double-distilled water as intracanal medication, and will be operated with REP using allogeneic stem cells in a scaffold, while the control group will be operated with conventional endodontic therapy alone. This clinical trial pretends to determine the dental survival of the tooth with mature apex and apical lesion, over a period of one year.

Official Title
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Encapsulated Mesenchymal Stem Cells for Endodontic Treatment of Permanent Teeth With Apical Lesion: a Controlled Clinical Trial.

Conditions
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Periapical Periodontitis

Intervention / Treatment
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* Procedure: Regenerative Endodontic Procedure
* Procedure: Conventional Root Canal Treatment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient inclusion criteria: Age: 16 - 58 years old. Signed the informed consent. Non-smoking. Systemically healthy patients Tooth inclusion criteria: Upper and lower incisors, upper and lower canines and lower premolars teeth with mature apex and apical lesion (greater than 2 PAI and 1 CBCTPAI). Teeth that do not response to both electrical and thermal pulp test Teeth that can be restored (as defined by Class A or Class B using Samet and Jotkowitz classification) without the need of a stainless steel crown. Exclusion Criteria: Patient exclusion criteria: Patients without a phone number for contact during the study. Subjects not available for follow up period (12 months). Patients who are or will undergo orthodontic treatment over the next 12 months. Patients with an allergy to any material or drug used in the study. Patients who are pregnant or lactating. Patients with a history of systemic diseases that alter immune function, such as diabetes mellitus, immunodeficiency, leukemia, Addison's disease and Cushing. Patients who have used immunosuppressive drugs or chemotherapy, 3 months before the study. Tooth exclusion criteria: Endodontically treated teeth Teeth with signs of severe root resorption. Teeth with mobility class III or Dens invaginatus. Teeth with avulsion history and conservation in a dry extraoral medium for more than 1 hour. Teeth with clinical and / or radiographic evidence of root fracture. Teeth that can not be absolutely isolated with rubber dam. . Teeth with more than one root or root canal.

Ages Eligible for Study
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Minimum Age: 16 Years
Maximum Age: 58 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: 2 interventions: Endodontic regenerative treatment with Biological product of umbilical cord-derived mesenchymal stem cells encapsulated in a plasma-derived biomaterial. Endodontic treatment with inert product gutapercha.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Regenerative Endodontic Procedure (REP)<br>umbilical cord-derived mesenchymal stem cells encapsulated in a plasma-derived biomaterial. | Procedure: Regenerative Endodontic Procedure<br>* Coronary access, conductometry, mechanized instrumentation, irrigation with sodium hypochlorite, intracanal calcium hydroxide medication and obturation with stem cells.<br>* Other names: Tissue engineering procedure;|
| Active Comparator: Conventional Root Canal Treatment<br>Conventional endodontic procedure | Procedure: Conventional Root Canal Treatment<br>* Coronary access, conductometry, mechanized instrumentation, irrigation with sodium hypochlorite, intracanal calcium hydroxide medication and obturation with gutta-percha.<br>* Other names: Gold standard treatment;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participats Showing Efficacy (Functionality) | Efficacy (functionality) was defined when one year after the intervention, the treated tooth remains in the mouth, without pain to percussion test and with apical bone lesion of equal size in the three senses of space or a decrease in some of them or no more than 0.1 mm increase of one of them. | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Pulpal Response | Change in pulpal response (period 1 year) will be assessed through response to sensitivity tests (cold, hot and electrical test) in teeth treated with regenerative procedure and conventional endodontic treatment during time. | baseline, 6 months, 12 months | 
| Change in Apical Lesion Size | Change in apical lesion size will be evaluated by cone beam tomography 6 and 12 months after intervention is completed. | baseline, 6 months, 12 months | 
| Pain to Percussion | To compare pain to percussion in a period of 1 year in permanent teeth with mature apex and apical lesion, treated with a regenerative endodontic procedure and conventional endodontic therapy. This will be monitored 6 and 12 months after the procedure is completed. Pain to percussion positive: The tooth is tenderness when is softly tapped with handle end of a dental mirror at examination time. Pain to percussion negative: The tooth is not tenderness when is softly tapped with handle end of a dental mirror at examination time. | baseline, 6 months, 12 months | 
| Numbers of Participants With Adverse Event | To describe adverse events in a period of 1 year in permanent teeth with mature apex and apical lesion, operated with a regenerative endodontic procedure and conventional endodontic therapy. | 6 months, 12 months | 
| Pulp Regeneration | To describe the pulp regeneration by means of vitality test using Doppler laser flowmetry (LDF) in a period of 1 year in permanent teeth with mature apex and apical lesion treated with a regenerative endodontic procedure. The vitality of the teeth was measured by LDF and the perfusion units (PU) percentage of the tooth under study was determined with respect to a healthy control tooth with similar anatomical characteristics from the same patient. | baseline, 6 months, 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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umbilical cord stem cells, mesenchymal stem cells, regenerative procedures, tissue engineering, regenerative endodontic, scaffold, cell encapsulation, dental pulp, pulp regeneration, plasma-derived biomaterial, allogenic stem cells, mesenchymal stromal cells, adult stem cells