Symptomatic Apical PeriodontitisNCT07437612
Cryotherapy and Intracanal Medicaments for Postoperative Pain in Apical Periodontitis
A study testing Placement of calcium hydroxide as an intracanal medicament, Placement of metformin as an intracanal medicament and Application of calcium hydroxide as an intracanal medicament together with intracanal cryotherapy in people with Symptomatic Apical Periodontitis and Pulp Necrosis, run by Celalettin Topbaş at 1 site in Turkey (Türkiye).
Trial summary
This randomized, participant- and outcome assessor-blinded, 2 × 2 factorial clinical trial evaluated the effects of intracanal cryotherapy and two intracanal medicaments-calcium hydroxide and metformin-on postoperative spontaneous and percussion pain in mandibular premolars with pulpal necrosis and symptomatic apical… Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Symptomatic Apical Periodontitis, Pulp Necrosis
- What is being tested?
- Placement of calcium hydroxide as an intracanal medicament, Placement of metformin as an intracanal medicament and Application of calcium hydroxide as an intracanal medicament together with intracanal cryotherapy
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 80 participants
- Where
- 1 siteTurkey (Türkiye)
- Study dates
- 1 Mar 2023to 1 Jan 2024
- Phase
- Interventional
- 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 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Systemically healthy participants. Mandibular premolar teeth diagnosed with pulpal necrosis and symptomatic apical periodontitis and indicated for root canal treatment.
- Periapical index (PAI) score of 1 or 2. Aged between 18 and 70 years. Able to understand and complete visual analog scale (VAS) assessments. Provided written informed consent.
Who cannot join
- Any systemic disease or pregnancy. Use of analgesics within 24 hours prior to treatment. Severe bruxism. Presence of acute apical abscess or swelling. Periodontal pocket depth greater than 5 mm or tooth mobility exceeding grade 1. Teeth deemed unrestorable. Presence of vital pulpal tissue or immature apices. Radiographic evidence of root resorption, root fracture, perforation, or canal calcification.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Effect of Intracanal Cryotherapy and Metformin on Postoperative Pain in Teeth With Symptomatic Apical Periodontitis: A Randomized Clinical Trial
This randomized, participant- and outcome assessor-blinded, 2 × 2 factorial clinical trial evaluated the effects of intracanal cryotherapy and two intracanal medicaments-calcium hydroxide and metformin-on postoperative spontaneous and percussion pain in mandibular premolars with pulpal necrosis and symptomatic apical periodontitis. Eighty participants were randomly assigned to four groups: calcium hydroxide, metformin, cryotherapy plus calcium hydroxide, and cryotherapy plus metformin. All teeth underwent standardized two-visit root canal treatment. In the cryotherapy groups, final irrigation at the first treatment visit was performed using sterile saline at 4 °C. Spontaneous pain was assessed preoperatively and daily for 7 postoperative days using a 100-mm visual analog scale (VAS). Percussion pain was assessed preoperatively and on day 7 immediately before the second treatment visit. The effects of cryotherapy, intracanal medicament type, and their interaction were evaluated using mixed-effects modeling for spontaneous pain and analysis of covariance (ANCOVA) for day-7 percussion pain.
- Conditions
- Symptomatic Apical Periodontitis, Pulp Necrosis
- Being tested
- Placement of calcium hydroxide as an intracanal medicament, Placement of metformin as an intracanal medicament, Application of calcium hydroxide as an intracanal medicament together with intracanal cryotherapy, Application of metformin into the canal together with intracanal cryotherapy
- Keywords
- Periapical Periodontitis, Metformin, Calcium Hydroxide, Intracanal Cryotherapy
- Medical subject headings
- Dental Pulp Necrosis, Periapical Periodontitis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Placement of calcium hydroxide as an intracanal medicamentDrug
Calcium hydroxide was applied into the canal after root canal shaping
Placement of metformin as an intracanal medicamentDrug
Application of metformin as an intracanal medicament following root canal shaping
Application of calcium hydroxide as an intracanal medicament together with intracanal cryotherapyDrug
Intracanal cryotherapy with 4 °C sterile saline was applied after root canal shaping and before calcium hydroxide placement.
Application of metformin into the canal together with intracanal cryotherapyDrug
Intracanal cryotherapy with 4 °C sterile saline was applied after root canal shaping and before metformin placement.
| Study group | Role | What they receive |
|---|---|---|
| Calcium Hydroxide | Active comparator | Not described Receives: Drug: Placement of calcium hydroxide as an intracanal medicament |
| Metformin | Active comparator | Not described Receives: Drug: Placement of metformin as an intracanal medicament |
| Intracanal Cryotherapy and Calcium Hydroxide | Active comparator | Not described Receives: Drug: Application of calcium hydroxide as an intracanal medicament together with intracanal cryotherapy |
| Intracanal Cryotherapy and Metformin | Active comparator | Not described Receives: Drug: Application of metformin into the canal together with intracanal cryotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Spontaneous postoperative pain on days 1 to 7
Spontaneous postoperative pain assessed daily from day 1 to day 7 using a Visual Analog Scale (VAS). Preoperative VAS score is used as a covariate in the statistical analysis.
Measured: Days 1 through 7 post-treatment
Secondary outcomes (1)
Day-7 percussion pain
Percussion pain assessed on day 7 immediately before the second treatment visit using a Visual Analog Scale (VAS). Preoperative percussion VAS score is used as a covariate in the statistical analysis.
Measured: Day 7 post-treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Feb 2026
- Study start1 Mar 2023
- Primary completion1 Jan 2024
- Study completion1 Jan 2024
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 Symptomatic Apical PeriodontitisStudies 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Model description
- In this randomized, factorial (2 × 2) clinical trial, 80 patients diagnosed with symptomatic apical periodontitis in mandibular premolar teeth were included. Patients were randomly allocated to four groups: calcium hydroxide, metformin, cryotherapy + calcium hydroxide, and cryotherapy + metformin. All teeth underwent standardized two-visit root canal treatment. Postoperative pain was assessed after the first visit, and day-7 outcomes were recorded immediately before the second treatment visit.
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 80 participants (actual)
Sponsor and investigators
- Lead sponsor
- Celalettin Topbaş
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Celalettin Topbaş, Saglik Bilimleri Universitesi
- Investigators
- Ali O ILHAN, DDS, Study chair, Saglik Bilimleri University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07437612
- Sponsor's protocol ID
- BSL5R6DP90
- Status last verified
- Sep 2026
- First submitted
- 30 Jan 2026
- Last updated
- 16 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Deidentified individual participant data underlying the results reported in the publication may be made available by the corresponding author upon reasonable request, subject to applicable ethical and institutional requirements.
Publications
Tan Y, Chen J, Jiang Y, Chen X, Li J, Chen B, Gao J. The anti-periodontitis action of metformin via targeting NLRP3 inflammasome. Arch Oral Biol. 2020 Jun;114:104692. doi: 10.1016/j.archoralbio.2020.104692. Epub 2020 Mar 4.
PubMed 32305805
Study at a glance
From the registry record, last updated by the sponsor on 16 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Intracanal Cryotherapy and Metformin on Postoperative Pain in Teeth With Symptomatic Apical Periodontitis: A Randomized Clinical Trial
- ClinicalTrials.gov ID
- NCT07437612
- Acronym / sponsor ID
- BSL5R6DP90
- Conditions
- Symptomatic Apical Periodontitis, Pulp Necrosis
- Keywords
- Periapical Periodontitis, Metformin, Calcium Hydroxide, Intracanal Cryotherapy
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 80 participants (actual)
- Lead sponsor
- Celalettin TopbaşUniversity, hospital or other
- Study start
- 1 Mar 2023 (actual)
- Primary completion
- 1 Jan 2024 (actual)
- Study completion
- 1 Jan 2024 (actual)
- First posted
- 27 Feb 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.
This randomized, participant- and outcome assessor-blinded, 2 × 2 factorial clinical trial evaluated the effects of intracanal cryotherapy and two intracanal medicaments-calcium hydroxide and metformin-on postoperative spontaneous and percussion pain in mandibular premolars with pulpal necrosis and symptomatic apical periodontitis. Eighty participants were randomly assigned to four groups: calcium hydroxide, metformin, cryotherapy plus calcium hydroxide, and cryotherapy plus metformin. All teeth underwent standardized two-visit root canal treatment. In the cryotherapy groups, final irrigation at the first treatment visit was performed using sterile saline at 4 °C. Spontaneous pain was assessed preoperatively and daily for 7 postoperative days using a 100-mm visual analog scale (VAS). Percussion pain was assessed preoperatively and on day 7 immediately before the second treatment visit. The effects of cryotherapy, intracanal medicament type, and their interaction were evaluated using mixed-effects modeling for spontaneous pain and analysis of covariance (ANCOVA) for day-7 percussion pain.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 4
- Model description
- In this randomized, factorial (2 × 2) clinical trial, 80 patients diagnosed with symptomatic apical periodontitis in mandibular premolar teeth were included. Patients were randomly allocated to four groups: calcium hydroxide, metformin, cryotherapy + calcium hydroxide, and cryotherapy + metformin. All teeth underwent standardized two-visit root canal treatment. Postoperative pain was assessed after the first visit, and day-7 outcomes were recorded immediately before the second treatment visit.
| Arm | Type | Receives |
|---|---|---|
| Calcium Hydroxide | Active comparator | Drug: Placement of calcium hydroxide as an intracanal medicament |
| Metformin | Active comparator | Drug: Placement of metformin as an intracanal medicament |
| Intracanal Cryotherapy and Calcium Hydroxide | Active comparator | Drug: Application of calcium hydroxide as an intracanal medicament together with intracanal cryotherapy |
| Intracanal Cryotherapy and Metformin | Active comparator | Drug: Application of metformin into the canal together with intracanal cryotherapy |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Systemically healthy participants. Mandibular premolar teeth diagnosed with pulpal necrosis and symptomatic apical periodontitis and indicated for root canal treatment.
- Periapical index (PAI) score of 1 or 2. Aged between 18 and 70 years. Able to understand and complete visual analog scale (VAS) assessments. Provided written informed consent.
Key exclusion criteria (1 listed)
- Any systemic disease or pregnancy. Use of analgesics within 24 hours prior to treatment. Severe bruxism. Presence of acute apical abscess or swelling. Periodontal pocket depth greater than 5 mm or tooth mobility exceeding grade 1. Teeth deemed unrestorable. Presence of vital pulpal tissue or immature apices. Radiographic evidence of root resorption, root fracture, perforation, or canal calcification.
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 |
|---|---|---|
| Placement of calcium hydroxide as an intracanal medicamentCalcium hydroxide was applied into the canal after root canal shaping | Drug | Calcium Hydroxide |
| Placement of metformin as an intracanal medicamentApplication of metformin as an intracanal medicament following root canal shaping | Drug | Metformin |
| Application of calcium hydroxide as an intracanal medicament together with intracanal cryotherapyIntracanal cryotherapy with 4 °C sterile saline was applied after root canal shaping and before calcium hydroxide placement. | Drug | Intracanal Cryotherapy and Calcium Hydroxide |
| Application of metformin into the canal together with intracanal cryotherapyIntracanal cryotherapy with 4 °C sterile saline was applied after root canal shaping and before metformin placement. | Drug | Intracanal Cryotherapy and Metformin |
Primary outcome
Spontaneous postoperative pain on days 1 to 7
Time frame: Days 1 through 7 post-treatment
Spontaneous postoperative pain assessed daily from day 1 to day 7 using a Visual Analog Scale (VAS). Preoperative VAS score is used as a covariate in the statistical analysis.
1 secondary outcome
Day-7 percussion pain
Time frame: Day 7 post-treatment
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 16 Sep 2026.
- Background: PubMed 32305805Tan Y, Chen J, Jiang Y, Chen X, Li J, Chen B, Gao J. The anti-periodontitis action of metformin via targeting NLRP3 inflammasome. Arch Oral Biol. 2020 Jun;114:104692. doi: 10.1016/j.archoralbio.2020.104692. Epub 2020 Mar 4.
- Individual participant dataSharing planned: Yes. Deidentified individual participant data underlying the results reported in the publication may be made available by the corresponding author upon reasonable request, subject to applicable ethical and institutional requirements.
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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. This study is not recruiting at the moment.
Ali O ILHAN, DDS study chair
Saglik Bilimleri University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Placement of calcium hydroxide as an intracanal medicament, Placement of metformin as an intracanal medicament and Application of calcium hydroxide as an intracanal medicament together with intracanal cryotherapy in people with Symptomatic Apical Periodontitis and Pulp Necrosis, run by Celalettin Topbaş at 1 site in Turkey (Türkiye).
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 2 inclusion and 1 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 16 Sep 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 Turkey (Türkiye). 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?
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?
Spontaneous postoperative pain on days 1 to 7 (time frame: Days 1 through 7 post-treatment). 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 NCT07437612, 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 16 Sep 2026.