Pulpal NecrosisNCT02477358
The Use of Platelet Rich Fibrin in Pulpal and Periodontal Regeneration in Mature Teeth
A study testing Left Tooth Platelet Rich Fibrin; Right Tooth Implant Alone and Right Tooth Platelet Rich Fibrin; Left Tooth Implant Alone in people with Pulpal Necrosis, run by University of Nebraska at 1 site in United States.
Trial summary
In cases of permanent tooth avulsion, it is widely accepted that some necrosis always occurs after avulsion injury. If the pulp tissue does not revascularize or if endodontic therapy is not performed, the pulp space can become infected. Read more about this study
- Who is it for?
- Ages 19 years and olderHealthy volunteers can take part
- Conditions the study is for
- Pulpal Necrosis
- What is being tested?
- Left Tooth Platelet Rich Fibrin; Right Tooth Implant Alone and Right Tooth Platelet Rich Fibrin; Left Tooth Implant Alone
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 1 siteUnited States
- Study dates
- 29 Sep 2014to 1 Jun 2016
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 19 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- any adult with single rooted vital teeth previously treatment planned for extraction to meet their prosthetic or orthodontic needs.
Who cannot join
- exclusion criteria will include: individuals with systemic illnesses that could compromise vascularity or healing,
- patients who are pregnant,
- or bisphosphonates.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Nebraska, College of Dentistry
Lincoln, Nebraska, 68505
About this study
In cases of permanent tooth avulsion, it is widely accepted that some necrosis always occurs after avulsion injury. If the pulp tissue does not revascularize or if endodontic therapy is not performed, the pulp space can become infected. Platelet rich fibrin (PRF) is a second generation platelet concentrate that allows the clinician to obtain fibrin membranes enriched with platelets and growth factors from an anticoagulant-free blood harvest. Clinical relevance of PRF and revascularization has been demonstrated in several case studies of avulsion. To date no human clinical trials have been performed evaluating the effectiveness of PRF on pulpal revascularization after reimplantation and its benefits in limiting inflammation. The following study consists of two phases: Phase 1: An in vitro model evaluating the effects of PRF in limiting inflammatory response of pdl cell cultures in the presence of an inflammatory mediators. Phase 2: An in vivo model utilizing mature teeth previously treatment planned for extraction, treating with PRF, reimplanting teeth and following for three to four months before extracting and performing histological analysis. If PRF is capable of promoting revascularization in mature teeth the potential benefits extend to limiting the need for endodontic therapy following mature tooth avulsion, potential for mature tooth transplantation in situations of congenitally missing teeth, and utilization of PRF in endodontic revascularization therapy.
Read the detailed description
When a tooth is avulsed, it is separated from its socket causing damage to the attachment apparatus. The periodontal ligament (pdl) is a group of specialized connective tissue fibers that attaches the cementum of the root (outer layer) to the alveolar bone. Avulsion can cause damage to the pdl and possible cemental tears. If the periodontal ligament is left attached to the root and minimal time lapse occurs damage to the tissues is usually limited. In these cases, reimplantation is a widely accepted treatment; however the long term success of an avulsed tooth is dependent on various factors. When excessive drying occurs prior to re-implantation, a severe inflammatory response is elicited directly on the root surface which may result in osseous replacement or replacement resorption. Some necrosis always occurs after avulsion injury, and while the necrotic pulp is of little consequence, this necrotic tissue is at high risk for bacterial contamination. If the pulp tissue does not revascularize or if endodontic therapy is not performed, the pulp space can become infected. It has been suggested that treatment strategies should attempt to limit peri-radicular inflammation therefore promoting favorable cemental healing and limiting unfavorable osseous replacement.
Platelet rich fibrin (PRF) is a second generation platelet concentrate that allows the clinician to obtain fibrin membranes enriched with platelets and growth factors from an anticoagulant-free blood harvest and without the addition of artificial biochemical modification. PRF has demonstrated clinical relevance through its ability to stimulate cell proliferation of osteoblasts, gingival fibroblasts, and periodontal ligament (PDL) cells. In addition, PRF has been shown to limit epithelial cell growth therefore promoting connective tissue and alveolar bone regeneration and inhibiting epithelial proliferation. These properties make it a favorable product for surgical procedures requiring micro vascularization.
In vitro studies with PRF and canine dental pulp cells demonstrate PRF's ability to promote chemotaxis and proliferation of the pulp cells and contributed to pulp repair. When PRF was combined with human dental pulp cells derived from extracted third molars it did not interfere with vitality and stimulated proliferation and differentiation. Additionally it upregulated the expression of osteoprotegerin and alkaline phosphatase.
Animal models evaluated PRF granules combined with human pdl stem cells and placed them on the root surface of freshly extracted canine teeth. The teeth were then reimplanted and evaluated histologically after a healing phase. A regeneration of the PDL-like tissue and reduction in ankylosis and inflammation were noted in animals with the PRF granules.
Clinical relevance of PRF and revascularization has been demonstrated in several case studies of avulsion. These case studies utilized a general protocol of minimally instrumenting the avulsed tooth. One study performed a 3 mm resection of the root apex followed by minimal instrumentation of the canal. Blood is then drawn from the patient and PRF is prepared via Choukroun's method. The PRF is then placed on the root surface and condensed into the canal. The tooth was then reimplanted, splinted, and the patient followed for up to 24 months. The tooth tested vital to thermal and percussion testing and radiographically did not show signs of replacement resorption or inflammation.
To date no human studies have been performed evaluating the effectiveness of PRF on pulpal revascularization after reimplantation and its benefits in limiting inflammation. Additionally, only histological evidence of the benefits of PRF has been demonstrated in animal models. If PRF is capable of promoting revascularization in mature teeth the potential benefits extend to limiting the need for endodontic therapy following mature tooth avulsion, potential for mature tooth transplantation in situations of congenitally missing teeth, and utilization of PRF in endodontic revascularization therapy.
The following research would consist of two phases: Phase 1. An in vitro model evaluating the effects of PRF in limiting inflammatory response of pulp and pdl cell cultures in the presence of an inflammatory mediators. Phase 2. An in vivo model utilizing mature teeth previously treatment planned for extraction, treating in accordance to the procedure documented by one group, reimplanting teeth and following for three to four months before extracting and performing histological analysis.
- Conditions
- Pulpal Necrosis
- Being tested
- Left Tooth Platelet Rich Fibrin; Right Tooth Implant Alone, Right Tooth Platelet Rich Fibrin; Left Tooth Implant Alone
- 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.
Left Tooth Platelet Rich Fibrin; Right Tooth Implant AloneProcedure or surgery
All study participants will have two teeth extracted and 2 mm of root removed. Half of the subjects will have platelet rich fibrin endodontic revascularization therapy will be applied to the left tooth socket only. The right tooth is implanted alone. Each tooth is replaced and splinted to the adjacent teeth. Teeth are followed for 3 months and then tested for vitality before extracting and examining histologically.
Right Tooth Platelet Rich Fibrin; Left Tooth Implant AloneProcedure or surgery
All study participants will have two teeth extracted and 2 mm of root removed. Half of the subjects will have platelet rich fibrin endodontic revascularization therapy to the right tooth socket only. The left tooth is implanted alone. Each tooth is replaced and splinted to the adjacent teeth. Teeth are followed for 3 months and then tested for vitality before extracting and examining histologically.
| Study group | Role | What they receive |
|---|---|---|
| PRF Treated | Experimental | Subjects will be randomized to either receive either left tooth platelet rich fibrin; right tooth implant alone, OR right tooth platelet rich fibrin; left tooth implant alone. Following treatment each tooth is replaced and splinted to the adjacent teeth. Teeth are followed for 3 months and then tested for vitality before extracting and examining histologically. Receives: Procedure: Left Tooth Platelet Rich Fibrin; Right Tooth Implant Alone; Procedure: Right Tooth Platelet Rich Fibrin; Left Tooth Implant Alone |
| Control | No intervention | Subjects will be randomized to either receive either left tooth platelet rich fibrin; right tooth implant alone, OR right tooth platelet rich fibrin; left tooth implant alone. Following treatment each tooth is replaced and splinted to the adjacent teeth. Teeth are followed for 3 months and then tested for vitality before extracting and examining histologically. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Vitality of Teeth (Units) Using Thermal and Percussion Sensitivity Trend Observed During Study Duration (3-11 Months)
Teeth (units) measuring vital via the following tests: thermal, percussion. Thermal was utilized with endo cold spray and percussion from tapping on teeth with mouth mirror.
Measured: 3-11 months. Each participant was measured for as long as it took to complete their prosthesis. The minimum study duration was 3 months and the maximum duration was 11 months in one subject.
Vitality of Teeth Using Electronic Pulp Test (EPT Units) Trend Observed During Study Duration (3-11 Months)
Teeth (units) measuring vital via the following tests: EPT utilizing EPT units (0-80). There is no specific number that suggests vital vs un-vital but rather it is a trend towards un-vital which is determined as 80.
Measured: 3-11 months. Each participant was measured for as long as it took to complete their prosthesis. The minimum study duration was 3 months and the maximum duration was 11 months in one subject.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jun 2015 (estimated)
- Study start29 Sep 2014
- Primary completion1 Jun 2016
- Study completion1 Jun 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Pulpal NecrosisStudies of the same condition, open and under way.
- More trials run by University of NebraskaThe sponsor's other registered studies.
- 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Model description
- Multiple teeth (2-6 teeth per participant) will be removed with the root attached and then half of the total teeth(per participant) will be placed back in the socket with Platelet Rich Fibrin (PRF) and the other half will be placed in the socket without PRF.
- Masking
- Double blind
- Who is masked
- Participant, Care provider
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Nebraska
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Elisabeth L Easley, DMD, Principal investigator, University of Nebraska
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02477358
- Sponsor's protocol ID
- 0443-14-FB
- Status last verified
- Sep 2023
- First submitted
- 26 May 2015
- Last updated
- 4 Oct 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Use of Platelet Rich Fibrin in Pulpal and Periodontal Regeneration in Mature Teeth
- ClinicalTrials.gov ID
- NCT02477358
- Acronym / sponsor ID
- 0443-14-FB
- Conditions
- Pulpal Necrosis
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- University of NebraskaUniversity, hospital or other
- Study start
- 29 Sep 2014 (actual)
- Primary completion
- 1 Jun 2016 (actual)
- Study completion
- 1 Jun 2016 (actual)
- First posted
- 22 Jun 2015 (estimated)
- Results
- Posted 20 Oct 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
In cases of permanent tooth avulsion, it is widely accepted that some necrosis always occurs after avulsion injury. If the pulp tissue does not revascularize or if endodontic therapy is not performed, the pulp space can become infected. Platelet rich fibrin (PRF) is a second generation platelet concentrate that allows the clinician to obtain fibrin membranes enriched with platelets and growth factors from an anticoagulant-free blood harvest. Clinical relevance of PRF and revascularization has been demonstrated in several case studies of avulsion. To date no human clinical trials have been performed evaluating the effectiveness of PRF on pulpal revascularization after reimplantation and its benefits in limiting inflammation. The following study consists of two phases: Phase 1: An in vitro model evaluating the effects of PRF in limiting inflammatory response of pdl cell cultures in the presence of an inflammatory mediators. Phase 2: An in vivo model utilizing mature teeth previously treatment planned for extraction, treating with PRF, reimplanting teeth and following for three to four months before extracting and performing histological analysis. If PRF is capable of promoting revascularization in mature teeth the potential benefits extend to limiting the need for endodontic therapy following mature tooth avulsion, potential for mature tooth transplantation in situations of congenitally missing teeth, and utilization of PRF in endodontic revascularization therapy.
Detailed description
When a tooth is avulsed, it is separated from its socket causing damage to the attachment apparatus. The periodontal ligament (pdl) is a group of specialized connective tissue fibers that attaches the cementum of the root (outer layer) to the alveolar bone. Avulsion can cause damage to the pdl and possible cemental tears. If the periodontal ligament is left attached to the root and minimal time lapse occurs damage to the tissues is usually limited. In these cases, reimplantation is a widely accepted treatment; however the long term success of an avulsed tooth is dependent on various factors. When excessive drying occurs prior to re-implantation, a severe inflammatory response is elicited directly on the root surface which may result in osseous replacement or replacement resorption. Some necrosis always occurs after avulsion injury, and while the necrotic pulp is of little consequence, this necrotic tissue is at high risk for bacterial contamination. If the pulp tissue does not revascularize or if endodontic therapy is not performed, the pulp space can become infected. It has been suggested that treatment strategies should attempt to limit peri-radicular inflammation therefore promoting favorable cemental healing and limiting unfavorable osseous replacement.
Platelet rich fibrin (PRF) is a second generation platelet concentrate that allows the clinician to obtain fibrin membranes enriched with platelets and growth factors from an anticoagulant-free blood harvest and without the addition of artificial biochemical modification. PRF has demonstrated clinical relevance through its ability to stimulate cell proliferation of osteoblasts, gingival fibroblasts, and periodontal ligament (PDL) cells. In addition, PRF has been shown to limit epithelial cell growth therefore promoting connective tissue and alveolar bone regeneration and inhibiting epithelial proliferation. These properties make it a favorable product for surgical procedures requiring micro vascularization.
In vitro studies with PRF and canine dental pulp cells demonstrate PRF's ability to promote chemotaxis and proliferation of the pulp cells and contributed to pulp repair. When PRF was combined with human dental pulp cells derived from extracted third molars it did not interfere with vitality and stimulated proliferation and differentiation. Additionally it upregulated the expression of osteoprotegerin and alkaline phosphatase.
Animal models evaluated PRF granules combined with human pdl stem cells and placed them on the root surface of freshly extracted canine teeth. The teeth were then reimplanted and evaluated histologically after a healing phase. A regeneration of the PDL-like tissue and reduction in ankylosis and inflammation were noted in animals with the PRF granules.
Clinical relevance of PRF and revascularization has been demonstrated in several case studies of avulsion. These case studies utilized a general protocol of minimally instrumenting the avulsed tooth. One study performed a 3 mm resection of the root apex followed by minimal instrumentation of the canal. Blood is then drawn from the patient and PRF is prepared via Choukroun's method. The PRF is then placed on the root surface and condensed into the canal. The tooth was then reimplanted, splinted, and the patient followed for up to 24 months. The tooth tested vital to thermal and percussion testing and radiographically did not show signs of replacement resorption or inflammation.
To date no human studies have been performed evaluating the effectiveness of PRF on pulpal revascularization after reimplantation and its benefits in limiting inflammation. Additionally, only histological evidence of the benefits of PRF has been demonstrated in animal models. If PRF is capable of promoting revascularization in mature teeth the potential benefits extend to limiting the need for endodontic therapy following mature tooth avulsion, potential for mature tooth transplantation in situations of congenitally missing teeth, and utilization of PRF in endodontic revascularization therapy.
The following research would consist of two phases: Phase 1. An in vitro model evaluating the effects of PRF in limiting inflammatory response of pulp and pdl cell cultures in the presence of an inflammatory mediators. Phase 2. An in vivo model utilizing mature teeth previously treatment planned for extraction, treating in accordance to the procedure documented by one group, reimplanting teeth and following for three to four months before extracting and performing histological analysis.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Double blind (participant, care provider)
- Number of arms
- 2
- Model description
- Multiple teeth (2-6 teeth per participant) will be removed with the root attached and then half of the total teeth(per participant) will be placed back in the socket with Platelet Rich Fibrin (PRF) and the other half will be placed in the socket without PRF.
| Arm | Type | Receives |
|---|---|---|
| PRF Treated | Experimental | Procedure: Left Tooth Platelet Rich Fibrin; Right Tooth Implant Alone, Procedure: Right Tooth Platelet Rich Fibrin; Left Tooth Implant AloneSubjects will be randomized to either receive either left tooth platelet rich fibrin; right tooth implant alone, OR right tooth platelet rich fibrin; left tooth implant alone. Following treatment each tooth is replaced and splinted to the adjacent teeth. Teeth are followed for 3 months and then tested for vitality before extracting and examining histologically. |
| Control | No intervention | –Subjects will be randomized to either receive either left tooth platelet rich fibrin; right tooth implant alone, OR right tooth platelet rich fibrin; left tooth implant alone. Following treatment each tooth is replaced and splinted to the adjacent teeth. Teeth are followed for 3 months and then tested for vitality before extracting and examining histologically. |
Who may qualify
- Ages
- 19 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- any adult with single rooted vital teeth previously treatment planned for extraction to meet their prosthetic or orthodontic needs.
Key exclusion criteria (3 listed)
- exclusion criteria will include: individuals with systemic illnesses that could compromise vascularity or healing,
- patients who are pregnant,
- or bisphosphonates.
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 |
|---|---|---|
| Left Tooth Platelet Rich Fibrin; Right Tooth Implant AloneAll study participants will have two teeth extracted and 2 mm of root removed. Half of the subjects will have platelet rich fibrin endodontic revascularization therapy will be applied to the left tooth socket only. The right tooth is implanted alone. Each tooth is replaced and splinted to the adjacent teeth. Teeth are followed for 3 months and then tested for vitality before extracting and examining histologically. | Procedure or surgery | PRF Treated |
| Right Tooth Platelet Rich Fibrin; Left Tooth Implant AloneAll study participants will have two teeth extracted and 2 mm of root removed. Half of the subjects will have platelet rich fibrin endodontic revascularization therapy to the right tooth socket only. The left tooth is implanted alone. Each tooth is replaced and splinted to the adjacent teeth. Teeth are followed for 3 months and then tested for vitality before extracting and examining histologically. | Procedure or surgery | PRF Treated |
Primary outcome
Vitality of Teeth (Units) Using Thermal and Percussion Sensitivity Trend Observed During Study Duration (3-11 Months)
Time frame: 3-11 months. Each participant was measured for as long as it took to complete their prosthesis. The minimum study duration was 3 months and the maximum duration was 11 months in one subject.
Teeth (units) measuring vital via the following tests: thermal, percussion. Thermal was utilized with endo cold spray and percussion from tapping on teeth with mouth mirror.
Vitality of Teeth Using Electronic Pulp Test (EPT Units) Trend Observed During Study Duration (3-11 Months)
Time frame: 3-11 months. Each participant was measured for as long as it took to complete their prosthesis. The minimum study duration was 3 months and the maximum duration was 11 months in one subject.
Teeth (units) measuring vital via the following tests: EPT utilizing EPT units (0-80). There is no specific number that suggests vital vs un-vital but rather it is a trend towards un-vital which is determined as 80.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Oct 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
Related trials for Pulpal 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
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
Not yet recruiting
The Effect of Bitewing Radiography on Outcomes and Costs of Treating Caries in Permanent Teeth
Dental Caries, Teeth Loss
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.
Elisabeth L Easley, DMD principal investigator
University of Nebraska
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Left Tooth Platelet Rich Fibrin; Right Tooth Implant Alone and Right Tooth Platelet Rich Fibrin; Left Tooth Implant Alone in people with Pulpal Necrosis, run by University of Nebraska at 1 site 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 1 inclusion and 3 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 4 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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.
Are results available for this study?
Yes. Results are posted in the registry (first posted 20 Oct 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Vitality of Teeth (Units) Using Thermal and Percussion Sensitivity Trend Observed During Study Duration (3-11 Months) (time frame: 3-11 months. Each participant was measured for as long as it took to complete their prosthesis. The minimum study duration was 3 months and the maximum duration was 11 months in one subject.). The study lists 2 primary outcomes in all. 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 4 Oct 2023.