Pulp NecrosisPhase 1NCT01976065
Regeneration of Pulp-Dentin Development in Teeth With Necrotic Pulps and Immature Roots
A Phase 1 study testing Triple Antibiotic Paste and Standard Treatment in people with Pulp Necrosis and Regeneration, run by Kenneth Hargreaves at 4 sites in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 6 to 20 yearsHealthy volunteers can take part
- Conditions the study is for
- Pulp Necrosis, Regeneration
- What is being tested?
- Triple Antibiotic Paste and Standard Treatment
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 125 participants
- Where
- 4 sitesUnited States
- Study dates
- Sep 2014to 24 Sep 2018
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 to 20 years
- All sexes
- Healthy volunteers accepted
- Child, Adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 12Show fewer
- 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.
Trial locations and contacts
4 sites in 1 country.
United States4 sites
University of Maryland
Baltimore, Maryland, 21201
University of North Carolina
Chapel Hill, North Carolina, 27599
Loma Linda University
Loma Linda, California, 92350
University of Texas Health Science Center
San Antonio, Texas, 78229
About this study
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.
Read the 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.
- Conditions
- Pulp Necrosis, Regeneration
- Being tested
- Triple Antibiotic Paste, Standard Treatment
- Keywords
- Necrotic tooth pulp, Immature permanent teeth, Regeneration
- Medical subject headings
- Dental Pulp Necrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Triple Antibiotic PasteDrug
Also called Ciprofloxacin, Metronidazole, & Minocycline
USP antibiotic drugs mixed at a 1:1:1 ratio into a powder that is mixed with sterile saline to a paste-like consistency
Standard TreatmentOther
Also called No use of study drug
Standard Treatment no use of study drug
| Study group | Role | What they receive |
|---|---|---|
| Mineral Trioxide Aggregate (MTA) | Other | 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). Receives: Other: Standard Treatment |
| Revascularization Treatment (REVASC) | Experimental | 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. Receives: Drug: Triple Antibiotic Paste |
| Regeneration Treatment (REGENDO) | Experimental | 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. Receives: Drug: Triple Antibiotic Paste |
What is being measured
The primary outcome is the main question the study is designed to answer.
Tooth Survival
- 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.
Measured: 2 years
Secondary outcomes (1)
Positive pulpal response
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.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Nov 2013 (estimated)
- Study startSep 2014
- Primary completion24 Sep 2018
- Study completion24 Sep 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pulp NecrosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- None (open label)
- Enrolment
- 125 participants (actual)
Sponsor and investigators
- Lead sponsor
- Kenneth Hargreaves
- Sponsor type
- University, hospital or other
- Collaborators
- University of Maryland, Baltimore, Loma Linda University, University of North Carolina, American Association of Endodontists
- Responsible party
- Sponsor-investigator, Kenneth Hargreaves, The University of Texas Health Science Center at San Antonio
- Investigators
- Kenneth Hargreaves, DDS, PhD, Study chair, University of Texas
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01976065
- Sponsor's protocol ID
- HSC20130467H
- Status last verified
- Sep 2023
- First submitted
- 29 Oct 2013
- Last updated
- 7 Sep 2023
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No: No plan to share data at this time.
Study at a glance
From the registry record, last updated by the sponsor on 7 Sep 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Regeneration of Pulp-Dentin Development in Teeth With Necrotic Pulps and Immature Roots
- ClinicalTrials.gov ID
- NCT01976065
- Acronym / sponsor ID
- HSC20130467H
- Conditions
- Pulp Necrosis, Regeneration
- Keywords
- Necrotic tooth pulp, Immature permanent teeth, Regeneration
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 125 participants (actual)
- Lead sponsor
- Kenneth HargreavesUniversity, hospital or other
- Collaborators
- University of Maryland, Baltimore, Loma Linda University, University of North Carolina, American Association of Endodontists
- Study start
- Sep 2014 (actual)
- Primary completion
- 24 Sep 2018 (actual)
- Study completion
- 24 Sep 2018 (actual)
- First posted
- 5 Nov 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Mineral Trioxide Aggregate (MTA) | Other | Other: Standard TreatmentStandard 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). |
| Revascularization Treatment (REVASC) | Experimental | Drug: Triple Antibiotic PasteConsists 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. |
| Regeneration Treatment (REGENDO) | Experimental | Drug: Triple Antibiotic PasteConsists 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. |
Who may qualify
- Ages
- 6 to 20 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult
Key inclusion criteria (7 listed)
- 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).
Key exclusion criteria (12 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Triple Antibiotic PasteAlso: Ciprofloxacin, Metronidazole, & MinocyclineUSP antibiotic drugs mixed at a 1:1:1 ratio into a powder that is mixed with sterile saline to a paste-like consistency | Drug | Regeneration Treatment (REGENDO), Revascularization Treatment (REVASC) |
| Standard TreatmentAlso: No use of study drugStandard Treatment no use of study drug | Other | Mineral Trioxide Aggregate (MTA) |
Primary outcome
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.
1 secondary outcome
Positive pulpal response
Time frame: 2 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Sep 2023.
- Individual participant dataSharing planned: No. No plan to share data at this time.
Related trials for Pulp Necrosis
Not yet recruiting
Post-operative Pain and Clinical Outcome After Single-cone Obturation With a Calcium Silicate-based Versus Epoxy Resin Sealer
Post Operative Pain, Acute, Irreversible Pulpitis (Toothache)
Not yet recruiting
PRP-Assisted Regenerative Endodontics Versus Conventional Root Canal Treatment in Mature Necrotic Teeth
Pulp Necrosis, Apical Periodontitis
Not yet recruiting
Influence of Continuous Rotation Versus Reciprocation Motion of MG3 Blue Rotary File on Postoperative Pain and Intracanal Bacterial Reduction of Teeth With Necrotic Pulps.
Necrotic Pulps With no Apical Periodontitis
Not yet recruiting
Clinical and Inflammatory Outcomes of Regenerative Endodontic Treatment Using Injectable Platelet-Rich Fibrin in Mature Necrotic Teeth With Chronic Apical Periodontitis.
Chronic Apical Periodontitis, Pulp Necrosis
Recruiting
Conventional and Nano-Metronidazole Irrigation With/Without Activation in Necrotic Teeth With Apical Periodontitis
Pulp Necrosis, Apical Periodontitis
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kenneth Hargreaves, DDS, PhD study chair
University of Texas
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Triple Antibiotic Paste and Standard Treatment in people with Pulp Necrosis and Regeneration, run by Kenneth Hargreaves at 4 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Tooth Survival (time frame: 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Sep 2023.