Encapsulated Mesenchymal Stem Cells for Dental Pulp Regeneration. (RanoKure)

• ClinicalTrials.gov Identifier: NCT03102879
• Recruitment Status: Completed
• First Posted: April 6, 2017
• Results First Posted: January 21, 2020
• Last Update Posted: January 21, 2020
• Sponsor: Universidad de los Andes, Chile
• Collaborator: Cells for Cells, Chile
• Information provided by (Responsible Party): Dra. Claudia Brizuel, Universidad de los Andes, Chile

Tracking Information

• First Submitted Date: March 21, 2017
• First Posted Date: April 6, 2017
• Results First Submitted Date: December 10, 2019
• Results First Posted Date: January 21, 2020
• Last Update Posted Date: January 21, 2020
• Actual Study Start Date: September 23, 2016
• Actual Primary Completion Date: September 30, 2018 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 16, 2020)

Number of Participats Showing Efficacy (Functionality) [ Time Frame: 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.

Original Primary Outcome Measures (submitted: March 30, 2017)

Tooth survival [ Time Frame: 24 months ]

• Survival (period 2 years): The primary outcome measure for this study is to evaluate the survival of the tooth through the retention of the tooth in the mouth. This parameter will be evaluated 24 months after the intervention is completed.

Current Secondary Outcome Measures (submitted: January 16, 2020)

• Change in Pulpal Response [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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.

Original Secondary Outcome Measures (submitted: March 30, 2017)

• Change in pulpal response [ Time Frame: baseline, 1 week, 3 months, 6 months, 12 months, 24 months. ]
  • Change in pulpal response (period 2 years) will be assessed through sensitivity tests (cold, heat and electricity), and laser doppler flow cytometry. The pulp status will be evaluated 1 week after intervention is completed, then at 3, 6, 12, and 24 months.
• Change in apical lesion size [ Time Frame: baseline, 6 months, 12 months, 18 months, 24 months. ]
  • Change in apical lesion size will be evaluated by standardized periapical radiography at 6,12, 18 and 24 months after intervention is completed. It will also be evaluated by Cone Beam 12 months after the procedure.
• Change in symptoms [ Time Frame: baseline, 1 week, 3 months, 6 months, 12 months, 24 months. ]
  • Change in symptoms will be evaluated with percussion of the tooth. This will be monitored 1 week after the operation is completed, then at 3, 6, 12 and 24 months.
• Change in tooth color [ Time Frame: baseline, 12 months, 24 months. ]
  This will be evaluated comparing the color and translucency differences, between teeth with REP and the standard procedure. This will be normalized with the corresponding control teeth from each patient. This will be monitored 12 and 24 months after the operation is completed.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Encapsulated Mesenchymal Stem Cells for Dental Pulp Regeneration.
• Official Title: Encapsulated Mesenchymal Stem Cells for Endodontic Treatment of Permanent Teeth With Apical Lesion: a Controlled Clinical Trial.
• 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.
• Study Type: Interventional
• Study Phase: Not Applicable

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
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.

Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment

• Condition: Periapical Periodontitis

Intervention

• Procedure: Regenerative Endodontic Procedure
  Coronary access, conductometry, mechanized instrumentation, irrigation with sodium hypochlorite, intracanal calcium hydroxide medication and obturation with stem cells.
  Other Names:

  • REP
  • Tissue engineering procedure
• Procedure: Conventional Root Canal Treatment
  Coronary access, conductometry, mechanized instrumentation, irrigation with sodium hypochlorite, intracanal calcium hydroxide medication and obturation with gutta-percha.
  Other Name: Gold standard treatment

Study Arms

• Experimental: Regenerative Endodontic Procedure (REP)
  umbilical cord-derived mesenchymal stem cells encapsulated in a plasma-derived biomaterial.
  Intervention: Procedure: Regenerative Endodontic Procedure
• Active Comparator: Conventional Root Canal Treatment
  Conventional endodontic procedure
  Intervention: Procedure: Conventional Root Canal Treatment

• Publications *: Brizuela C, Meza G, Urrejola D, Quezada MA, Concha G, Ramirez 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: January 16, 2020): 36
• Original Estimated Enrollment (submitted: March 30, 2017): 40
• Actual Study Completion Date: September 30, 2018
• Actual Primary Completion Date: September 30, 2018 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 16 Years to 58 Years (Child, Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Chile

Administrative Information

• NCT Number: NCT03102879
• Other Study ID Numbers: RPD-8-16
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

IPD Sharing Statement

• Plan to Share IPD: Undecided

• Current Responsible Party: Dra. Claudia Brizuel, Universidad de los Andes, Chile
• Original Responsible Party: Same as current
• Current Study Sponsor: Universidad de los Andes, Chile
• Original Study Sponsor: Same as current
• Collaborators: Cells for Cells, Chile
• Investigators: Not Provided
• PRS Account: Universidad de los Andes, Chile
• Verification Date: January 2020