Comparison of Tissue in Regenerative Endodontic Procedures and Apexification

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01805388
Recruitment Status : Withdrawn (Lack of pediatric recruitment ability)
First Posted : March 6, 2013
Last Update Posted : February 5, 2016
Information provided by (Responsible Party):
Kenneth Hargreaves, The University of Texas Health Science Center at San Antonio

Brief Summary:
The purpose of our study is to characterize the composition of the hard and soft tissues present after regenerative endodontic procedures in root canals of teeth previously diagnosed with the need for extraction for orthodontic treatment and incomplete root formation. Although the protocol addressed in this study is currently being used in clinical practice, there are no prospective clinical trials investigating its efficacy in stimulating continued root development and the nature of the newly formed tissues.

Condition or disease Intervention/treatment Phase
Dental Pulp Regeneration Drug: Experimental: Regeneration Treatment Group Procedure: Control Non-Study Drug Group Phase 1

Detailed Description:
Twenty subjects with permanent bilateral premolar teeth with incomplete root development and scheduled for extraction due to orthodontic requirement will be treated with a regeneration protocol. Teeth (n=20/group) will be extracted at 3 months following the regenerative protocol or the pulpectomy control. The protocol relies on disinfection of the canal space by copious irrigation with common endodontic irrigants and placement of a triple antibiotic paste (regenerative group) or calcium hydroxide dressing (control group) to disinfect the root for a period of one month. In each patient, both treatment arms will be performed. Thus, each treatment sample will have a contralateral matching control (paired designs). At the end of one month, the intracanal medicaments (triple antibiotic paste) is irrigated out of the canal and a blood clot is stimulated in the canal with the aid of endodontic files that are introduced into the periapical tissues; this blood clot will serve as a scaffold for tissue proliferation within the canal. The regenerative treatment tooth is then restored to prevent bacteria from the oral cavity from re-contaminating the canal space. For the contralateral control tooth, the medication will remain in the tooth until the extraction date. The subjects in this study will have the treated teeth extracted at 3 months after initial treatment. The extracted teeth from each study participant will be placed in storage medium until Immunohistochemical analysis with antibodies to characterize the tissue/cells within the canal.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: Comparison of Tissue Formation in Regenerative Endodontic Procedures and Apexification
Study Start Date : February 2013
Actual Primary Completion Date : October 2015
Actual Study Completion Date : October 2015

Arm Intervention/treatment
Experimental: Regeneration Treatment Group
RTC with Triple Antibiotic Study Drug
Drug: Experimental: Regeneration Treatment Group
Regenerative Root Canal Therapy using Triple Antibiotic Paste study drug
Other Name: Regenerative RTC using Triple Antibiotic Paste study drug

Procedure: Control Non-Study Drug Group
Endodontic RTC with no study drug
Other Name: Root Canal Therapy

No Intervention: Control Non-study Drug Group
RTC on contralateral tooth with no study drug

Primary Outcome Measures :
  1. Histological identification of the mineralized tissue at the apical third of the root and the adherent cellular layer. [ Time Frame: Following tooth extraction at the 3 month followup visit. Correlation of all data collected from the extracted teeth will occur at the completion of the study at year 5. ]
    Although we predict histological identification of dentin/odontoblasts (due to the proximity of the apical papilla and associated SCAP stem cells) using our scanning laser confocal microscopy system, our methods are sufficiently sensitive to permit identification of bone/osteoblasts and cementum/cementoblasts as alternative hypotheses.

Secondary Outcome Measures :
  1. Whether stem cells enter the canal space when bleeding is stimulated through manipulation of the apical papilla. [ Time Frame: Canal bleeding is evoked during the second treatment visit thirty days following the first treatment. Blood collected by paper points will be saved till the end of the study (year 5) for analysis. ]
    This secondary outcome measure will be conducted by measuring markers of stem cells prior to and after the formation of the blood clot. We predict that evoking bleeding into the root canal system will increase the delivery of mesenchymal stem cells.

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Ages Eligible for Study:   9 Years to 18 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes

Inclusion Criteria:

Patient Inclusion Criteria:

  • Children ages 9-18 with bilateral premolars with incomplete root development scheduled for extraction for orthodontic reasons.
  • Children who seem to be cooperative with dental treatment and able to indicate willingness to obtain treatment and participate in the study and who are capable of verbally expressing dissent.
  • Parents who express understanding of study treatments and consent to treatment for their child of the regenerative procedure prior to the tooth extraction for orthodontic reasons .
  • Healthy patients (ASA Class I or II physical status) with no systemic health problems that may interfere with healing and cell growth.

Tooth inclusion criteria:

  • Permanent premolar teeth with immature root development and healthy pulps scheduled for extraction due to orthodontic requirements.
  • Clinically confirmed teeth with good periodontal health assessed by periodontal probing depths of less than 4mm.

Exclusion Criteria:

Patient Exclusion Criteria:

  • Parents and patients unable to give consent or express dissent.
  • Patients who are unwilling to undergo the research and orthodontic dental treatment.
  • Patients affected by tempromandibular joint disorders.
  • Patients affected by known orofacial pain disorders.
  • Patients with ASA Class III or IV physical status (Immuno-compromised patients including patients who self-report that they are an HIV carrier, undergoing steroid therapy or chemotherapy, or those who self-report with genetic or systemic diseases that could result in reduced immune response).

Tooth Exclusion Criteria:

  • Teeth with vertical cracks that extend below the cemento-enamel junction.
  • Teeth that cannot be isolated using a rubber dam.
  • Teeth with non-odontogenic pathology.
  • Teeth whose apices are fully developed, as determined radiographically and correlated with dental age of patient.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01805388

United States, Texas
University of Texas Health Science Center
San Antonio, Texas, United States, 78229
Sponsors and Collaborators
Kenneth Hargreaves
Principal Investigator: Anibal R Diogenes, DDS, PhD The University of Texas Health Science Center at San Antonio
Principal Investigator: Dubravko Pavlin, DMD, PhD University of Texas Health Science Center San Antonio
Principal Investigator: Kenneth M Hargreaves, DDS, PhD University of Texas Health Science Center San Antonio

Responsible Party: Kenneth Hargreaves, Sponsor-Investigator, The University of Texas Health Science Center at San Antonio Identifier: NCT01805388     History of Changes
Other Study ID Numbers: HSC20130054H
First Posted: March 6, 2013    Key Record Dates
Last Update Posted: February 5, 2016
Last Verified: February 2016

Keywords provided by Kenneth Hargreaves, The University of Texas Health Science Center at San Antonio:
Dental Pulp Regeneration

Additional relevant MeSH terms:
Anti-Bacterial Agents
Polymyxin B
Bacitracin zinc, neomycin sulfate, polymyxin B, drug combination
Antibiotics, Antitubercular
Anti-Infective Agents
Antitubercular Agents
Anti-Infective Agents, Local
Protein Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action