Regeneration of Pulp-Dentin Development in Teeth With Necrotic Pulps and Immature Roots

• ClinicalTrials.gov Identifier: NCT01976065
• Recruitment Status: Completed
• First Posted: November 5, 2013
• Last Update Posted: September 7, 2023
• Sponsor: Kenneth Hargreaves
• Collaborators: University of Maryland, Baltimore; Loma Linda University; University of North Carolina; American Association of Endodontists
• Information provided by (Responsible Party): Kenneth Hargreaves, The University of Texas Health Science Center at San Antonio

Tracking Information

• First Submitted Date: October 29, 2013
• First Posted Date: November 5, 2013
• Last Update Posted Date: September 7, 2023
• Actual Study Start Date: September 2014
• Actual Primary Completion Date: September 24, 2018 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 29, 2013)

Tooth Survival [ Time Frame: 2 years ]

1) the growth in hard tissue deposition in the radiographic root area is increased by at least 20%, and 2) the tooth survives to this time point and 3) there is no pain.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: October 29, 2013)

Positive pulpal response [ Time Frame: 2 years ]

Comparison of treatment effects on positive pulpal responses, crown staining, preoperative factors (age, sex, history of trauma), or antimicrobial efficacy and residual intracanal microbial load would influence the primary outcome measure of tooth survival.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Regeneration of Pulp-Dentin Development in Teeth With Necrotic Pulps and Immature Roots
• Official Title: Regeneration of Pulp-Dentin Development in Teeth With Necrotic Pulps and Immature Roots
• Brief Summary: This multi-center exploratory clinical trial is a randomized trial designed to test whether a regenerative endodontic procedure using tissue engineering principles (REGENDO), or a revascularization (REVASC) endodontic procedure, in comparison to standard apexification treatment using a mineral trioxide aggregate barrier (apexification; APEX), produces a significantly better composite clinical outcome for the treatment of immature permanent teeth with pulpal necrosis.
• Detailed Description: This is a multi-center randomized clinical trial designed to test whether a regenerative endodontic procedure using tissue engineering principles (REGENDO), or a revascularization (REVASC) endodontic procedure, when compared to the standard apexification treatment using mineral trioxide aggregate barrier-MTA apexification (APEX), produces a significantly better composite clinical outcome for the treatment of immature permanent teeth with pulpal necrosis. This study will use an antibiotic mixture called Triple Antibiotic Paste (TAP), consisting of ciprofloxacin, metronidazole and minocycline, in the tooth for disinfection of the root canal in study arms REGENDO and REVASC. The FDA has issued an Investigational New Drug (IND) number allowing use of the triple antibiotic mixture in this trial. Other dental materials used in this study have already been FDA approved for use in humans to provide a matrix for the promotion of tissue growth in the root canal space. The study will also attempt to identify the type of bacteria within the root canal space and surrounding tissues by analyzing a small sample collected on a cotton-tip applicator. This clinical trial hopes to determine which of the three treatment methods helps the tooth to grow stronger and survive for at least two years after treatment.
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Randomized; Intervention Model: Factorial Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Pulp Necrosis
• Regeneration

Intervention

• Drug: Triple Antibiotic Paste
  USP antibiotic drugs mixed at a 1:1:1 ratio into a powder that is mixed with sterile saline to a paste-like consistency
  Other Name: Ciprofloxacin, Metronidazole, & Minocycline
• Other: Standard Treatment
  Standard Treatment no use of study drug
  Other Name: No use of study drug

Study Arms

• Mineral Trioxide Aggregate (MTA)
  Standard Treatment group consisting of placement of Mineral Trioxide Aggregate (MTA), an FDA approved dental material at the end of an immature root followed by a composite restoration (crown).
  Intervention: Other: Standard Treatment
• Experimental: Revascularization Treatment (REVASC)
  Consists of standard treatment procedure PLUS disinfection of the canal space with Triple Antibiotic Paste study medication followed by placement of Collaplug, an FDA approved material to help promote clotting. A composite restoration in then placed.
  Intervention: Drug: Triple Antibiotic Paste
• Experimental: Regeneration Treatment (REGENDO)
  Consists of standard treatment procedure PLUS Triple Antibiotic Paste study medication PLUS use of Emdogain, an FDA approved medication used in an FDA approved manner, that is a growth factor to help surrounding tissues to grow together and heal.
  Intervention: Drug: Triple Antibiotic Paste

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: October 1, 2018): 125
• Original Estimated Enrollment (submitted: October 29, 2013): 120
• Actual Study Completion Date: September 24, 2018
• Actual Primary Completion Date: September 24, 2018 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Age 6-20
• Participant has a permanent tooth with a necrotic pulp (as defined by lack of responsiveness to both electrical pulp tests and cold [EndoIce] tests). If the tooth was traumatized, then pulpal necrosis is defined as either: 1) no response to both electrical pulp test and cold [EndoIce] test by three months after trauma, or 2) presence of a periapical lesion, or 3) radiographic evidence of root resorption, or 4) discoloration of the crown.
• Tooth in question is restorable (as defined by Class A or Class B using Samet and Jotkowitz classification) without the need of a stainless steel crown.
• Incomplete (i.e., immature) root development defined by apical foramen ≥1.0mm (each foramina >1.0mm for multi-rooted teeth).
• At least 5 mm of root development (CEJ to radiographic apex).
• Willing and able to provide informed assent/consent.
• Legal guardian willing and able to provide informed consent.

Exclusion Criteria:

• No access to telephone for study contacts.
• Unable to comprehend study materials in English or Spanish.
• Subject not available for follow up at 12 or 24 months.
• Previous allergic response to ciprofloxacin, metronidazole or minocycline or any materials used in the study.
• History of systemic diseases with altered immune function including diabetes, immunodeficiency, leukemia, Addison's or Cushing's disease.
• History of taking immunosuppressants or chemotherapeutic agents including glucocorticoids in the past 3 months.
• Clinical or radiographic evidence of root fracture or alveolar fracture.
• Tooth in question received prior endodontic obturation.
• Tooth in question has class III mobility or dens invaginatus.
• Tooth in question has a history of avulsion with extra-oral dry time longer than 1 hour.
• Clinical judgement (with documentation of the reason)
• Radiographic or clinical identification of ankylosis (replacement resorption) or inflammatory (infection-related) root resorption.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 6 Years to 20 Years (Child, Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01976065
• Other Study ID Numbers: HSC20130467H
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: No
• Plan Description: No plan to share data at this time.

• Current Responsible Party: Kenneth Hargreaves, The University of Texas Health Science Center at San Antonio
• Original Responsible Party: Same as current
• Current Study Sponsor: Kenneth Hargreaves
• Original Study Sponsor: Same as current

Collaborators

• University of Maryland, Baltimore
• Loma Linda University
• University of North Carolina
• American Association of Endodontists

Investigators

• Study Chair: Kenneth Hargreaves, DDS, PhD; University of Texas

• PRS Account: The University of Texas Health Science Center at San Antonio
• Verification Date: September 2023