N-Acetyl Cysteine Protects Pulpal Stem Cells in Endodontic Revascularization (NAC)

N-Acetyl Cysteine Helps Pulp Stem Cells Differentiate During Endodontic Revascularization

Pulp re-vascularization/regeneration is a procedure performed to allow pulpal stem cells to survive and/or differentiate to allow immature tooth root structures to grow to full maturity. Currently, the procedure includes disinfection of the necrotic root canal space and induction of bleeding to potentiate pulpal stem cell differentiation to allow root growth on an immature root. A number of studies conducted previously demonstrate that N-acetyl cysteine (NAC) potentiates differentiation of pulpal stem/stromal cells and protects pulpal cells from apoptosis. 14-18 human subjects will be recruited forming two groups where pulp re-vascularization/regeneration procedures will be performed with or without the use of NAC treatment prior to induction of bleeding. Recall follow-up appointments will be done at 6 months and 1 year post treatment with subsequent yearly appointments until full root growth has been achieved.

Study Overview

• Status: Unknown
• Conditions: Endodontic Disease
• Intervention / Treatment: Drug: N acetyl cysteine

Detailed Description

We will recruit 14-18 patients under the age of 18 by means of advertising at UCLA. Two groups will be formed, one with NAC treatment during endodontic revascularization and one without. Each patient will have an adult tooth where the following criteria are met:

• Tooth with necrotic pulp and immature apex(apices)
• Pulp space is not needed for post/core, final restoration
• Compliant patient who is willing to come for at least 2-3 treatment appointments and 2-3 follow-up recall appointments.
• Patients are not allergic to calcium hydroxide intra-canal medicament

Appropriate consent forms will be obtained by the patient and the patient's parent or legal guardian. If we recruit 18 patient, 9 patients will be under regenerative endodontic therapy/re-vascularization with NAC and 9 patients without NAC.

The following procedures will be applied to the patients.

First Appointment:

• Local anesthesia administration, dental dam isolation and access
• Copious, gentle irrigation with 20mL NaOCL (sodium hypochlorite) using an irrigation system that minimizes the possibility of extrusion of irrigants into the periapical spaces. The concentration of NaOCL will be low (1.5%, 20mL/canal for 5 minutes). Afterwards, irrigation with 17% EDTA (20mL/canal for 5 minutes) will be done. Irrigating needle position should be about 1mm from root end, to minimize cytotoxicity to stem cells in the apical tissues.
• Dry canals with paper points
• Place calcium hydroxide into canal(s) delivered via syringe
• Seal access with 3-4mm of a temporary restorative material such as CavitTM, IRMTM or glass ionomer. Dismiss patient for 2-4 weeks.

Second Appointment:

• Assess response to initial treatment. If there are signs/symptoms of persistent infection, consider repeating the procedures of the First appointment.
• Anesthesia with 3% mepivacaine without vasoconstrictor, dental dam isolation
• Copious gentle irrigation with 20mL of 17% EDTA
• Take a radiograph to ensure previous calcium hydroxide has been fully removed form the canal system
• Dry with paper points
• For study patients only: Irrigate canal system with NAC (20mM NAC, 30mL/canal) gently for 10 minutes and then dry canal(s) with paper points
• Create bleeding into the canal system by over-instrumenting (endo file, endo explorer). Induce bleeding by rotating a pre-curved (approximately 45 degrees at the apical 1-2mm of file) K-file at 2mm past the apical foramen with the goal of having the entire canal filled with blood to the level of the cemento-enamel junction.
• Stop the bleeding at a level that allows for 3-4mm of restorative material. Place a resorbable matrix (CollaPlugTM, CollacoteTM, CollatTapeTM) over the blood clot if necessary to achieve a better stop for mineral trioxide aggregate (MTA) or Bioceramic fast set putty (BC). Place white MTA as capping material on top of the resorbable matrix.
• The access is closed with 3-4mm layer of glass ionomer (Fuji IXTM, GC America, Alsip, IL), composite or alloy over the capping material. For resin modified glass ionomers and composite, 40 seconds of light curer will be done.

Follow-up recall appointments: Clinical and Radiographic exam

• Extra-oral examination: No pain, extra-oral swelling nor extra-oral sinus tract
• Intra-oral examination: No pain, intra-oral swelling of mucosa nor intra-oral sinus tract
• Take 1 straight on periapical radiograph and 1 angled periapical radiograph. Resolution of apical radiolucency (often observed within 6-12months).
• Record any increased width of root walls (this is generally observed before apparent increase in root length and often occurs 12-24 months after treatment)
• Record any increase in root length (in mm)
• Test vitality of pulp with Endo-Ice and Electric pulp tester (EPT).
• Record which goals have been attained (primary, secondary and/or tertiary)

The degree of success of RET is measured by the extent to which it is possible to attain primary, secondary and tertiary goals:

• Primary goal: The elimination of symptoms and the evidence of bony healing
• Secondary goal: Increased root wall thickness and/or increased root length
• Tertiary goal: Positive response to vitality testing

• Study Type: Interventional
• Enrollment (Anticipated): 14
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: David C Han, DDS, MS; Phone Number: 3108254348; Email: dhan@dentistry.ucla.edu
• Study Contact Backup: Name: Anahid Jewett, PhD; Phone Number: 3108256528; Email: ajewett@dentistry.ucla.edu

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90095
      • Recruiting
      • University of California, Los Angeles Dept of Graduate Endodontics
      • Contact: David C Han, DDS, MS; Phone Number: 310-825-4348; Email: dhan@dentistry.ucla.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 years to 16 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Inclusion criteria include the following:

  1. Subjects will be self and parent-reported as healthy individuals with no significant medical issues.
  2. Radiographic assessment will determine that root(s) have not grown to completion

  2) Vitality tests (cold testing with Endo ice and Electric pulp testing) will determine the tooth to be necrotic 3) Palpation and percussion tests may or may not be positive 4) Probings will be within 1-5mm 5) Patient will commit to coming to 2-3 treatment appointments lasting 1-3 hours each. Thereafter, patient will commit to come for followup recall appointments 6 and 12 months following last treatment appointment.

  6) Patient must be able to tolerate sitting in a dental chair for 1-3 hours. 7) Patient will be in the age range of 6 to 18 years

Exclusion Criteria:

• Exclusion criteria include patients who cannot tolerate sitting in a dental chair due to anxiety for 1-2 hours.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Control; No intervention will be administered in this group as it serves as a control group.
Experimental: NAC Treatment; N-Acetyl Cysteine treatment during root canal revascularization	Drug: N acetyl cysteine; N acetyl cysteine at 20mM will be utilized as the final stage of irrigation prior to induction of bleeding during endodontic revascularization procedure.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of Root length	Change of root length in millimeters over time	6 months and 1 year

Collaborators and Investigators

• Sponsor: University of California, Los Angeles
• Investigators: Principal Investigator: David C Han, DDS, MS, University of California, Los Angeles

Study record dates

Study Major Dates

• Study Start (Actual): June 15, 2018
• Primary Completion (Anticipated): June 15, 2020
• Study Completion (Anticipated): June 15, 2020

Study Registration Dates

• First Submitted: February 23, 2018
• First Submitted That Met QC Criteria: February 23, 2018
• First Posted (Actual): March 1, 2018

Study Record Updates

• Last Update Posted (Actual): October 30, 2019
• Last Update Submitted That Met QC Criteria: October 29, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Stomatognathic Diseases; Tooth Diseases; Dental Pulp Diseases; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Protective Agents; Respiratory System Agents; Antioxidants; Antidotes; Free Radical Scavengers; Expectorants; Acetylcysteine; N-monoacetylcystine
• Other Study ID Numbers: 17-001024

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No