Apical PeriodontitisPhase 4NCT07518901
Nanozymes in Endodontics
A Phase 4 study testing Nanozyme treatment in people with Apical Periodontitis and Endodontic Disease, run by University of Pennsylvania at 1 site in United States.
Trial summary
The antimicrobial efficacy and healing potential of clinically approved ferumoxytol nanozymes versus the standard 3% NaOCl irrigant will be evaluated in adults undergoing endodontic treatment. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Apical Periodontitis, Endodontic Disease, Root Canal Infection
- What is being tested?
- Nanozyme treatment
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 72 participants
- Where
- 1 siteUnited States
- Study dates
- 24 Aug 2026to Jun 2028
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients willing to participate in the study.
- Patients are 18 years or above.
- Non-contributory medical history (Patient can be seen for regular dental appointment in PDM; ASA classes I and II).
- Tooth requiring root canal treatment with radiographic presence of periapical radiolucency and
- responding to thermal sensitivity testing negatively (Difluordichlormethane at 50 °C, Endo-Ice,
- Coltène/Whaledent Inc., Cuyahoga Falls, Ohio) or a negative response to EPT testing.
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- Tooth with adequate remaining tooth structure for proper isolation with rubber dam.
- No history of previous endodontic treatment on the tooth.
- Teeth with single roots or multirooted teeth.
Who cannot join
- Self-reported pregnancy.
- Patients requiring antibiotic premedication prior to dental treatment.
- Patients with multiple drug allergies.
- Patients with known hypersensitivity to Ferumoxytol nanoparticles or any iron products.
- Patients who are scheduled for MRI for the head region within three months after Ferumoxytol nanoparticles application.
- Periodontal changes (pockets 3 mm, mobility Grade I, or gingival edema).
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- Patients who cannot return for a subsequent appointment or follow-ups.
- Radiographic presence of resorptive processes.
- Cracked and fractured teeth.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site
Penn Dental Medicine, Department of Endodontics
Philadelphia, Pennsylvania, 19104
About this study
Official title: Ferumoxytol Nanozymes for Biofilm Disruption: A Clinical Study
The antimicrobial efficacy and healing potential of clinically approved ferumoxytol nanozymes versus the standard 3% NaOCl irrigant will be evaluated in adults undergoing endodontic treatment. Building on prior protocols that demonstrated ferumoxytol nanozymes antimicrobial activity as a root canal irrigant, ferumoxytol solution will be applied topically, assessment of clinical and radiographical findings will determine its potential as a novel disinfection and its long-term outcome.
Read the detailed description
This study aims to fill critical knowledge gaps identified in prior clinical findings by optimizing the integration of nanozymes into endodontic workflows and thereby improving treatment outcomes for teeth with apical periodontitis. The study will evaluate the topical application of a low-dose ferumoxytol formulation (Feraheme/H2O2) within the prepared canal system of patients undergoing routine root canal therapy. Antimicrobial efficacy will be compared to the standard sodium hypochlorite irrigant via intracanal microbial sampling. Periapical tissue regeneration and long-term clinical outcomes will be assessed at 6-month and 1-year follow-up intervals using cone-beam computed tomography (CBCT).
- Being tested
- Nanozyme treatment, Control (Standard treatment)
- Keywords
- Nanozymes, Root canal irrigants, Nanotechnology, iron oxide nanoparticles
- Medical subject headings
- Periapical Periodontitis, Dental Pulp Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Nanozyme treatmentDrug
Also called Iron oxide nanoparticles, Feraheme, Ferumoxytol
Experimental arm: topical intra-canal irrigation with ferumoxytol (Feraheme®) diluted to 6 mg/mL in 0.1 M sodium acetate, activated with 3% H₂O₂. The solution is instilled into an isolated, dried canal, physically agitated for ~60 s to promote nanozyme activation and convective mixing, held for a brief contact time (<10 min), then aspirated per SOP; post-treatment intracanal sterile paper-point samples are collected. Topical nanozyme mechanism (catalytic ROS generation from low-dose H₂O₂), defined low topical dose and brief contact time (non-systemic).
Control (Standard treatment)Drug
Also called NaOCl, Sodium hypochlorite
Control arm: standard clinical irrigation with 3% sodium hypochlorite (NaOCl) using matched total volume and institutional activation method, with identical pre/post sampling and follow-up.
| Study group | Role | What they receive |
|---|---|---|
| Nanozyme treatment | Experimental | After access preparation with sterile burs and sterile saline irrigation and working length determination, 2 mL of a mixture of Ferumoxytol (6mg/mL)/H2O2(3%) will be introduced into the canal. The root canal systems will be instrumented with XP-Shaper rotary files, a total of 8 mL of solution will be used, and a total contact time of 10 minutes. Receives: Drug: Nanozyme treatment |
| Sodium hypochlorite | Active comparator | After access preparation with sterile burs and sterile saline irrigation and working length determination, 2 mL of a mixture of sodium hypochlorite (NaOCl) will be introduced into the canal. The root canal systems will be instrumented with XP-Shaper rotary files, a total of 8 mL of NaOCl solution will be used, and a total contact time of 10 minutes. Receives: Drug: Control (Standard treatment) |
What is being measured
The primary outcome is the main question the study is designed to answer.
The change in bacterial count between the experimental group (Ferumoxytol/H2O2) and the standard of care (NaOCl) group.
By measuring reduction in bacteria colony forming units (CFU) before and after treatment for the experimental group (Ferumoxytol/H2O2) and the standard of care (NaOCl) group, then comparing the two groups.
Samples 1-2 will be taken during the first root canal treatment visit. Sample 1 before cleaning or shaping the root canal. Sample 2 after cleaning and shaping of the root canal using laser or NaOCl. Sample 3 will be taken in the second visit, upon completion of final routine irrigation protocol.
Measured: 1 Year
Secondary outcomes (1)
Periapical Bone Changes from Baseline in Periapical Radiographs at 6, 12, and 24 Months Follow Up
Periapical radiographs will be taken at baseline (preoperative) then at 6 months follow up post root canal filling.
Radiographically, Following periapical index (PAI) by Órstavik 1986, description of radiographic findings:
- Normal periapical structures.
- Small changes in the bone structure.
- Change in the bone structure with mineral loss.
- Periodontitis with a well-defined radiolucent area.
- Severe periodontitis with exacerbating features. Success is defined as either complete (radiographic resolution of a periapical lesion - the radiographic sign of inflammatory processes surrounding a root tip) or incomplete healing (scar tissue formation) and failure includes uncertain healing (radiographic reduction of a periapical lesion or same lesion size) or unsatisfactory healing (increase in lesion size) as determined on the radiograph.
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 posted9 Apr 2026
- Study start24 Aug 2026
- Primary completionJun 2028 (estimated)
- Study completionJun 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Apical PeriodontitisStudies of the same condition, open and under way.
- More trials run by University of PennsylvaniaThe 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Outcomes assessor
- Enrolment
- 72 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Pennsylvania
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Bekir Karabucak, University of Pennsylvania
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07518901
- Sponsor's protocol ID
- 859377
- Status last verified
- Oct 2026
- First submitted
- 1 Apr 2026
- Last updated
- 13 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Only the participants chart numbers were collected during the study. The study protocol, statistical analysis plan, and informed consent form will be published as supporting information with the final manuscript
Publications
1. Kakehashi S, Stanley HR, Fitzgerald RJ. The effects of surgical exposures of dental pulps in germ-free and conventional laboratory rats. Oral Surgery, Oral Medicine, Oral Pathology. 1965/09/01/ 1965;20(3):340-349. doi:https://doi.org/10.1016/0030-4220(65)90166-0 2. Bergenholtz G. Micro-organisms from necrotic pulp of traumatized teeth. Odontol Revy. 1974;25(4):347-58. 3. Kerekes K, Tronstad L. Long-term results of endodontic treatment performed with a standardized technique. Journal of Endodontics. 1979/03/01/ 1979;5(3):83-90. doi:https://doi.org/10.1016/S0099-2399(79)80154-5 4. Bukhari S, Kim D, Liu Y, Karabucak B, Koo H. Novel Endodontic Disinfection Approach Using Catalytic Nanoparticles. J Endod. May 2018;44(5):806-812. doi:10.1016/j.joen.2017.12.003 5. Ricucci D, Siqueira JF, Jr. Biofilms and apical periodontitis: study of prevalence and association with clinical and histopathologic findings. J Endod. Aug 2010;36(8):1277-88. doi:10.1016/j.joen.2010.04.007 6. SJÖGREN U, FIGDOR D, PERSSON S, SUNDQVIST G. Influence of infection at the time of root filling on the outcome of endodontic treatment of teeth with apical periodontitis. International Endodontic Journal. 1997;30(5):297-306. doi:https://doi.org/10.1046/j.1365-2591.1997.00092.x 7. Ricucci D, Siqueira JF, Bate AL, Pitt Ford TR. Histologic Investigation of Root Canal-treated Teeth with Apical Periodontitis: A Retrospective Study from Twenty-four Patients. Journal of Endodontics. 2009/04/01/ 2009;35(4):493-502. doi:https://doi.org/10.1016/j.joen.2008.12.014 8. Babeer A, Liu Y, Ren Z, et al. Ferumoxytol nanozymes effectively target chronic biofilm infections in apical periodontitis. J Clin Invest. Nov 26 2024;doi:10.1172/jci183576 9. Huang Y, Liu Y, Pandey NK, et al. Iron oxide nanozymes stabilize stannous fluoride for targeted biofilm killing and synergistic oral disease prevention. Nature Communications. 2023/09/29 2023;14(1):6087. doi:10.1038/s41467-023-41687-8
Study at a glance
From the registry record, last updated by the sponsor on 13 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Ferumoxytol Nanozymes for Biofilm Disruption: A Clinical Study
- ClinicalTrials.gov ID
- NCT07518901
- Acronym / sponsor ID
- 859377
- Keywords
- Nanozymes, Root canal irrigants, Nanotechnology, iron oxide nanoparticles
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Enrolling by invitation
- Enrolment
- 72 participants (estimated)
- Lead sponsor
- University of PennsylvaniaUniversity, hospital or other
- Study start
- 24 Aug 2026 (actual)
- Primary completion
- Jun 2028 (estimated)
- Study completion
- Jun 2028 (estimated)
- First posted
- 9 Apr 2026 (actual)
- 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.
The antimicrobial efficacy and healing potential of clinically approved ferumoxytol nanozymes versus the standard 3% NaOCl irrigant will be evaluated in adults undergoing endodontic treatment. Building on prior protocols that demonstrated ferumoxytol nanozymes antimicrobial activity as a root canal irrigant, ferumoxytol solution will be applied topically, assessment of clinical and radiographical findings will determine its potential as a novel disinfection and its long-term outcome.
Detailed description
This study aims to fill critical knowledge gaps identified in prior clinical findings by optimizing the integration of nanozymes into endodontic workflows and thereby improving treatment outcomes for teeth with apical periodontitis. The study will evaluate the topical application of a low-dose ferumoxytol formulation (Feraheme/H2O2) within the prepared canal system of patients undergoing routine root canal therapy. Antimicrobial efficacy will be compared to the standard sodium hypochlorite irrigant via intracanal microbial sampling. Periapical tissue regeneration and long-term clinical outcomes will be assessed at 6-month and 1-year follow-up intervals using cone-beam computed tomography (CBCT).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Nanozyme treatment | Experimental | Drug: Nanozyme treatmentAfter access preparation with sterile burs and sterile saline irrigation and working length determination, 2 mL of a mixture of Ferumoxytol (6mg/mL)/H2O2(3%) will be introduced into the canal. The root canal systems will be instrumented with XP-Shaper rotary files, a total of 8 mL of solution will be used, and a total contact time of 10 minutes. |
| Sodium hypochlorite | Active comparator | Drug: Control (Standard treatment)After access preparation with sterile burs and sterile saline irrigation and working length determination, 2 mL of a mixture of sodium hypochlorite (NaOCl) will be introduced into the canal. The root canal systems will be instrumented with XP-Shaper rotary files, a total of 8 mL of NaOCl solution will be used, and a total contact time of 10 minutes. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Patients willing to participate in the study.
- Patients are 18 years or above.
- Non-contributory medical history (Patient can be seen for regular dental appointment in PDM; ASA classes I and II).
- Tooth requiring root canal treatment with radiographic presence of periapical radiolucency and
- Tooth with adequate remaining tooth structure for proper isolation with rubber dam.
Key exclusion criteria (9 listed)
- Self-reported pregnancy.
- Patients requiring antibiotic premedication prior to dental treatment.
- Patients with multiple drug allergies.
- Patients with known hypersensitivity to Ferumoxytol nanoparticles or any iron products.
- Patients who are scheduled for MRI for the head region within three months after Ferumoxytol nanoparticles application.
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 |
|---|---|---|
| Nanozyme treatmentAlso: Iron oxide nanoparticles, Feraheme, FerumoxytolExperimental arm: topical intra-canal irrigation with ferumoxytol (Feraheme®) diluted to 6 mg/mL in 0.1 M sodium acetate, activated with 3% H₂O₂. The solution is instilled into an isolated, dried canal, physically agitated for ~60 s to promote nanozyme activation and convective mixing, held for a brief contact time (<10 min), then aspirated per SOP; post-treatment intracanal sterile paper-point samples are collected. Topical nanozyme mechanism (catalytic ROS generation from low-dose H₂O₂), defined low topical dose and brief contact time (non-systemic). | Drug | Nanozyme treatment |
| Control (Standard treatment)Also: NaOCl, Sodium hypochloriteControl arm: standard clinical irrigation with 3% sodium hypochlorite (NaOCl) using matched total volume and institutional activation method, with identical pre/post sampling and follow-up. | Drug | Sodium hypochlorite |
Primary outcome
The change in bacterial count between the experimental group (Ferumoxytol/H2O2) and the standard of care (NaOCl) group.
Time frame: 1 Year
By measuring reduction in bacteria colony forming units (CFU) before and after treatment for the experimental group (Ferumoxytol/H2O2) and the standard of care (NaOCl) group, then comparing the two groups. Samples 1-2 will be taken during the first root canal treatment visit. Sample 1 before cleaning or shaping the root canal. Sample 2 after cleaning and shaping of the root canal using laser or NaOCl. Sample 3 will be taken in the second visit, upon completion of final routine irrigation protocol.
1 secondary outcome
Periapical Bone Changes from Baseline in Periapical Radiographs at 6, 12, and 24 Months Follow Up
Time frame: 2 Years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Oct 2026.
- Background1. Kakehashi S, Stanley HR, Fitzgerald RJ. The effects of surgical exposures of dental pulps in germ-free and conventional laboratory rats. Oral Surgery, Oral Medicine, Oral Pathology. 1965/09/01/ 1965;20(3):340-349. doi:https://doi.org/10.1016/0030-4220(65)90166-0 2. Bergenholtz G. Micro-organisms from necrotic pulp of traumatized teeth. Odontol Revy. 1974;25(4):347-58. 3. Kerekes K, Tronstad L. Long-term results of endodontic treatment performed with a standardized technique. Journal of Endodontics. 1979/03/01/ 1979;5(3):83-90. doi:https://doi.org/10.1016/S0099-2399(79)80154-5 4. Bukhari S, Kim D, Liu Y, Karabucak B, Koo H. Novel Endodontic Disinfection Approach Using Catalytic Nanoparticles. J Endod. May 2018;44(5):806-812. doi:10.1016/j.joen.2017.12.003 5. Ricucci D, Siqueira JF, Jr. Biofilms and apical periodontitis: study of prevalence and association with clinical and histopathologic findings. J Endod. Aug 2010;36(8):1277-88. doi:10.1016/j.joen.2010.04.007 6. SJÖGREN U, FIGDOR D, PERSSON S, SUNDQVIST G. Influence of infection at the time of root filling on the outcome of endodontic treatment of teeth with apical periodontitis. International Endodontic Journal. 1997;30(5):297-306. doi:https://doi.org/10.1046/j.1365-2591.1997.00092.x 7. Ricucci D, Siqueira JF, Bate AL, Pitt Ford TR. Histologic Investigation of Root Canal-treated Teeth with Apical Periodontitis: A Retrospective Study from Twenty-four Patients. Journal of Endodontics. 2009/04/01/ 2009;35(4):493-502. doi:https://doi.org/10.1016/j.joen.2008.12.014 8. Babeer A, Liu Y, Ren Z, et al. Ferumoxytol nanozymes effectively target chronic biofilm infections in apical periodontitis. J Clin Invest. Nov 26 2024;doi:10.1172/jci183576 9. Huang Y, Liu Y, Pandey NK, et al. Iron oxide nanozymes stabilize stannous fluoride for targeted biofilm killing and synergistic oral disease prevention. Nature Communications. 2023/09/29 2023;14(1):6087. doi:10.1038/s41467-023-41687-8
- Individual participant dataSharing planned: Yes. Only the participants chart numbers were collected during the study. The study protocol, statistical analysis plan, and informed consent form will be published as supporting information with the final manuscript
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Nanozyme treatment in people with Apical Periodontitis and Endodontic Disease, run by University of Pennsylvania 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 9 inclusion and 9 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: enrolling by invitation, as of the sponsor's last update on 13 Oct 2026. 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.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
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?
The change in bacterial count between the experimental group (Ferumoxytol/H2O2) and the standard of care (NaOCl) group. (time frame: 1 Year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07518901, which also lists 1 linked publication.
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 13 Oct 2026.