Periapical Periodontitis
Conditions
Keywords
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, umbilical cord stem cells
Brief summary
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
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.
Interventions
PROCEDURERegenerative Endodontic Procedure
Coronary access, conductometry, mechanized instrumentation, irrigation with sodium hypochlorite, intracanal calcium hydroxide medication and obturation with stem cells.
PROCEDUREConventional Root Canal Treatment
Coronary access, conductometry, mechanized instrumentation, irrigation with sodium hypochlorite, intracanal calcium hydroxide medication and obturation with gutta-percha.
Sponsors
Cells for Cells
Universidad de los Andes, Chile
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Intervention model description
2 interventions: 1. Endodontic regenerative treatment with Biological product of umbilical cord-derived mesenchymal stem cells encapsulated in a plasma-derived biomaterial. 2. Endodontic treatment with inert product gutapercha.
Eligibility
Sex/Gender
ALL
Age
16 Years to 58 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participats Showing Efficacy (Functionality) | 12 months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Pulpal Response | baseline, 6 months, 12 months | 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. |
| Change in Apical Lesion Size | baseline, 6 months, 12 months | Change in apical lesion size will be evaluated by cone beam tomography 6 and 12 months after intervention is completed. |
| Pain to Percussion | baseline, 6 months, 12 months | 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. |
| Numbers of Participants With Adverse Event | 6 months, 12 months | 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. |
| Pulp Regeneration | baseline, 6 months, 12 months | 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. |
Countries
Chile
Participant flow
Recruitment details
Recruitment between September 2016 and September 2017, from patients referred for endodontic treatment to the Universidad de los Andes Health Center, located in San Bernardo city, Santiago, Chile.
Participants by arm
| Arm | Count |
|---|---|
| Regenerative Procedure Endodontic regenerative treatment with biological product of umbilical cord-derived mesenchymal stem cells encapsulated in a plasma-derived biomaterial. | 18 |
| Endodontic Treatment Conventional root canal treatment treatment with inert product gutapercha. | 18 |
| Total | 36 |
Baseline characteristics
| Characteristic | Regenerative Procedure | Endodontic Treatment | Total |
|---|---|---|---|
| Age, Continuous | 27 years | 28 years | 27 years |
| Race and Ethnicity Not Collected | — | — | 0 Participants |
| Sex: Female, Male Female | 12 Participants | 13 Participants | 25 Participants |
| Sex: Female, Male Male | 6 Participants | 5 Participants | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 18 | 0 / 18 |
| other Total, other adverse events | 0 / 18 | 0 / 18 |
| serious Total, serious adverse events | 0 / 18 | 0 / 18 |
Outcome results
Primary
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.
Time frame: 12 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Regenerative Procedure | Number of Participats Showing Efficacy (Functionality) | 18 Participants |
| Endodontic Treatment | Number of Participats Showing Efficacy (Functionality) | 18 Participants |
Secondary
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.
Time frame: baseline, 6 months, 12 months
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Regenerative Procedure | Change in Apical Lesion Size | Basal Antero-Posterior | 5 milimeters |
| Regenerative Procedure | Change in Apical Lesion Size | 6 months Antero-Posterior | 2.4 milimeters |
| Regenerative Procedure | Change in Apical Lesion Size | Basal Height | 5.5 milimeters |
| Regenerative Procedure | Change in Apical Lesion Size | 12 months Mesio-Distal | 2 milimeters |
| Regenerative Procedure | Change in Apical Lesion Size | 12 months Height | 1.8 milimeters |
| Regenerative Procedure | Change in Apical Lesion Size | 6 months Mesio-Distal | 2.7 milimeters |
| Regenerative Procedure | Change in Apical Lesion Size | 12 months Anterio-Posterior | 2.1 milimeters |
| Regenerative Procedure | Change in Apical Lesion Size | Basal Mesio-Distal | 5 milimeters |
| Regenerative Procedure | Change in Apical Lesion Size | 6 months Height | 2.6 milimeters |
| Endodontic Treatment | Change in Apical Lesion Size | 12 months Mesio-Distal | 1.7 milimeters |
| Endodontic Treatment | Change in Apical Lesion Size | Basal Mesio-Distal | 5.5 milimeters |
| Endodontic Treatment | Change in Apical Lesion Size | Basal Height | 7.1 milimeters |
| Endodontic Treatment | Change in Apical Lesion Size | Basal Antero-Posterior | 5.1 milimeters |
| Endodontic Treatment | Change in Apical Lesion Size | 6 months Mesio-Distal | 2.4 milimeters |
| Endodontic Treatment | Change in Apical Lesion Size | 6 months Height | 2.5 milimeters |
| Endodontic Treatment | Change in Apical Lesion Size | 6 months Antero-Posterior | 3 milimeters |
| Endodontic Treatment | Change in Apical Lesion Size | 12 months Height | 1.5 milimeters |
| Endodontic Treatment | Change in Apical Lesion Size | 12 months Anterio-Posterior | 1.7 milimeters |
Secondary
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.
Time frame: baseline, 6 months, 12 months
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Regenerative Procedure | Change in Pulpal Response | Basal Cold Test | Response | 1 Participants |
| Regenerative Procedure | Change in Pulpal Response | Basal Cold Test | No Response | 17 Participants |
| Regenerative Procedure | Change in Pulpal Response | Basal Hot Test | Response | 0 Participants |
| Regenerative Procedure | Change in Pulpal Response | Basal Hot Test | No Response | 18 Participants |
| Regenerative Procedure | Change in Pulpal Response | Basal Electrical Test | Response | 3 Participants |
| Regenerative Procedure | Change in Pulpal Response | Basal Electrical Test | No Response | 15 Participants |
| Regenerative Procedure | Change in Pulpal Response | 6 months Cold Test | Response | 14 Participants |
| Regenerative Procedure | Change in Pulpal Response | 6 months Cold Test | No Response | 4 Participants |
| Regenerative Procedure | Change in Pulpal Response | 6 months Hot Test | Response | 2 Participants |
| Regenerative Procedure | Change in Pulpal Response | 6 months Hot Test | No Response | 16 Participants |
| Regenerative Procedure | Change in Pulpal Response | 6 months Electrical Test | Response | 4 Participants |
| Regenerative Procedure | Change in Pulpal Response | 6 months Electrical Test | No Response | 14 Participants |
| Regenerative Procedure | Change in Pulpal Response | 12 months Cold Test | Response | 10 Participants |
| Regenerative Procedure | Change in Pulpal Response | 12 months Cold Test | No Response | 8 Participants |
| Regenerative Procedure | Change in Pulpal Response | 12 months Hot Test | Response | 5 Participants |
| Regenerative Procedure | Change in Pulpal Response | 12 months Hot Test | No Response | 13 Participants |
| Regenerative Procedure | Change in Pulpal Response | 12 months Electrical Test | Response | 9 Participants |
| Regenerative Procedure | Change in Pulpal Response | 12 months Electrical Test | No Response | 9 Participants |
| Endodontic Treatment | Change in Pulpal Response | 12 months Cold Test | No Response | 17 Participants |
| Endodontic Treatment | Change in Pulpal Response | Basal Cold Test | Response | 1 Participants |
| Endodontic Treatment | Change in Pulpal Response | 6 months Hot Test | No Response | 18 Participants |
| Endodontic Treatment | Change in Pulpal Response | Basal Cold Test | No Response | 17 Participants |
| Endodontic Treatment | Change in Pulpal Response | 12 months Electrical Test | No Response | 15 Participants |
| Endodontic Treatment | Change in Pulpal Response | Basal Hot Test | Response | 1 Participants |
| Endodontic Treatment | Change in Pulpal Response | 6 months Electrical Test | Response | 4 Participants |
| Endodontic Treatment | Change in Pulpal Response | Basal Hot Test | No Response | 17 Participants |
| Endodontic Treatment | Change in Pulpal Response | 12 months Hot Test | Response | 0 Participants |
| Endodontic Treatment | Change in Pulpal Response | Basal Electrical Test | Response | 1 Participants |
| Endodontic Treatment | Change in Pulpal Response | 6 months Electrical Test | No Response | 14 Participants |
| Endodontic Treatment | Change in Pulpal Response | Basal Electrical Test | No Response | 17 Participants |
| Endodontic Treatment | Change in Pulpal Response | 12 months Electrical Test | Response | 3 Participants |
| Endodontic Treatment | Change in Pulpal Response | 6 months Cold Test | Response | 2 Participants |
| Endodontic Treatment | Change in Pulpal Response | 12 months Cold Test | Response | 1 Participants |
| Endodontic Treatment | Change in Pulpal Response | 6 months Cold Test | No Response | 16 Participants |
| Endodontic Treatment | Change in Pulpal Response | 12 months Hot Test | No Response | 18 Participants |
| Endodontic Treatment | Change in Pulpal Response | 6 months Hot Test | Response | 0 Participants |
Secondary
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.
Time frame: 6 months, 12 months
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Regenerative Procedure | Numbers of Participants With Adverse Event | 12 months | 0 Participants |
| Regenerative Procedure | Numbers of Participants With Adverse Event | 6 months | 0 Participants |
| Endodontic Treatment | Numbers of Participants With Adverse Event | 6 months | 0 Participants |
| Endodontic Treatment | Numbers of Participants With Adverse Event | 12 months | 0 Participants |
Secondary
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.
Time frame: baseline, 6 months, 12 months
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Regenerative Procedure | Pain to Percussion | 12 months Pain to Percussion | Positive | 0 Participants |
| Regenerative Procedure | Pain to Percussion | 12 months Pain to Percussion | Negative | 18 Participants |
| Regenerative Procedure | Pain to Percussion | Baseline Pain to Percussion | Positive | 11 Participants |
| Regenerative Procedure | Pain to Percussion | Baseline Pain to Percussion | Negative | 7 Participants |
| Regenerative Procedure | Pain to Percussion | 6 months Pain to Percussion | Positive | 1 Participants |
| Regenerative Procedure | Pain to Percussion | 6 months Pain to Percussion | Negative | 17 Participants |
| Endodontic Treatment | Pain to Percussion | 6 months Pain to Percussion | Positive | 0 Participants |
| Endodontic Treatment | Pain to Percussion | 12 months Pain to Percussion | Positive | 0 Participants |
| Endodontic Treatment | Pain to Percussion | Baseline Pain to Percussion | Negative | 13 Participants |
| Endodontic Treatment | Pain to Percussion | 12 months Pain to Percussion | Negative | 18 Participants |
| Endodontic Treatment | Pain to Percussion | 6 months Pain to Percussion | Negative | 18 Participants |
| Endodontic Treatment | Pain to Percussion | Baseline Pain to Percussion | Positive | 5 Participants |
Secondary
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.
Time frame: baseline, 6 months, 12 months
Population: This outcome was not measured in conventional treatment group due to the nature of the filling material, which does not promote revitalization of the pulp.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Regenerative Procedure | Pulp Regeneration | Basal | 60.6 % PU in time in relation to controltooth |
| Regenerative Procedure | Pulp Regeneration | 6 months | 74.4 % PU in time in relation to controltooth |
| Regenerative Procedure | Pulp Regeneration | 12 months | 78.1 % PU in time in relation to controltooth |