An interventional study of Intracanal cryotherapy and Room-temperature saline irrigation in Asymptomatic Apical Periodontitis, Endodontic Retreatment and Cryotherapy, sponsored by Alanya Alaaddin Keykubat University. Recruiting at 1 site in Turkey (Türkiye). Open to participants aged 18 Years to 65 Years. Per ClinicalTrials.gov, last updated 2026-10-27.
Sponsored by Alanya Alaaddin Keykubat University · Not applicable, Interventional, and Treatment
This prospective, randomized, controlled, single-blind, parallel-group clinical trial evaluates whether intracanal cryotherapy reduces postoperative pain and inflammatory biomarker levels following single-visit endodontic retreatment of teeth with asymptomatic apical periodontitis. A total of 100 patients (18-65 years, systemically healthy, ASA I-II) requiring non-surgical retreatment of a single-rooted mandibular premolar tooth will be randomly assigned via computer-generated randomization to one of two equal groups (n=50 each): a cryotherapy group, receiving intracanal final irrigation with sterile saline cooled to 2.5°C for 5 minutes, and a control group, receiving the same irrigation protocol with saline at room temperature (20-22°C). Salivary nerve growth factor (NGF) and gingival crevicular fluid (GCF) prostaglandin E2 (PGE2) levels will be measured by ELISA at baseline (T0), 24 hours (T1), and 72 hours (T2). Postoperative pain will be assessed using a visual analog scale (VAS, 0-100 mm) at 6, 12, 24, 48, and 72 hours and on day 7, with the 24-hour VAS score as the primary comparison point. Rescue analgesic (paracetamol) consumption will also be recorded and compared between groups. The study aims to determine whether intracanal cryotherapy lowers postoperative pain and biomarker levels compared to standard-temperature irrigation, and to evaluate the correlation between PGE2/NGF levels and pain intensity.
Postoperative pain following endodontic retreatment is associated with periapical inflammation mediated by prostaglandin E2 (PGE2) and nerve growth factor (NGF). Intracanal cryotherapy has been proposed to reduce postoperative pain through local hypothermia-induced vasoconstriction, neuropraxia, and reduced metabolic and inflammatory mediator activity. While prior studies have examined cryotherapy's effect on postoperative pain, no randomized controlled trial has jointly measured PGE2 and NGF using minimally invasive sampling methods (GCF and saliva) in the context of single-visit retreatment.
Eligible patients will be systemically healthy adults (18-65 years, ASA I-II) with a single-rooted mandibular premolar tooth requiring non-surgical retreatment due to a previously inadequate root canal treatment, presenting with asymptomatic apical periodontitis and periapical radiolucency (PAI ≥ 3). Key exclusion criteria include pregnancy or lactation, uncontrolled diabetes mellitus (HbA1c > 7%), autoimmune disease, immunosuppressive therapy, systemic corticosteroid use within the past 3 months, BMI > 35 kg/m², acute infection (abscess/cellulitis), advanced periodontal breakdown, heavy smoking (>10 cigarettes/day), recent analgesic/NSAID or antibiotic use, and chronic pain syndromes.
Patients will be randomly allocated (computer-generated randomization, sealed envelopes) to one of two parallel groups:
Group A (Cryotherapy): Following standard non-surgical retreatment instrumentation, final intracanal irrigation with sterile saline cooled to 2.5°C, 20 mL, over 5 minutes.
Group B (Control): Identical protocol using sterile saline at room temperature (20-22°C), 20 mL, over 5 minutes.
All treatments will be performed in a single visit by one calibrated operator following a standardized protocol; the two groups differ only in irrigation temperature. Given the nature of the intervention, the operator cannot be blinded; however, laboratory personnel analyzing saliva/GCF samples and statisticians will remain blinded to group allocation (single-blind design).
Outcome measures:
Primary: Postoperative pain intensity measured by VAS (0-100 mm) at 6, 12, 24, 48, and 72 hours and on day 7, with the 24-hour time point as the primary comparison.
Secondary: Salivary NGF levels (ELISA) and GCF PGE2 levels (ELISA) at baseline (T0), 24 hours (T1), and 72 hours (T2); rescue analgesic (paracetamol 500 mg, oral, as needed) consumption over 7 days; and correlation between biomarker levels and VAS pain scores.
Each patient will be followed for a total of 7 days. Saliva and GCF samples will be collected between 08:00-10:00 to minimize circadian variation. Sample size was calculated using G*Power 3.1.9.7 (repeated-measures ANOVA, 80% power, α=0.05, f=0.25), yielding a minimum of 34 participants per group; accounting for an estimated 20% dropout rate, 50 patients per group (100 total) will be enrolled. Statistical significance will be set at p\<0.05. The study is sponsored and funded internally by Alanya Alaaddin Keykubat University, with no external funding or industry sponsorship.
5,640 studies on the registry are indexed under Pain, Postoperative; 1,230 are open to participants now.
This study's planned enrollment of 100 is above the median of 75 across 4,821 interventional studies indexed under Pain, Postoperative.
Browse Pain, Postoperative studies →Alanya Alaaddin Keykubat University is the lead sponsor of 51 studies on the registry; 17 are open to participants now.
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Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
The anaesthetists’ scale of health before surgery: I is healthy, II has a mild illness that is under control, III a severe one, IV a severe illness that is a constant threat to life. V and VI are used for the critically ill and for organ donors.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
A blood test of average blood sugar over the past two to three months, given as a percentage or in mmol/mol. 6.5% (48 mmol/mol) or more is the usual threshold for diabetes, normally confirmed by a second test.
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
ASA physical status
The anaesthetists’ scale of health before surgery: I is healthy, II has a mild illness that is under control, III a severe one, IV a severe illness that is a constant threat to life. V and VI are used for the critically ill and for organ donors.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HbA1c
A blood test of average blood sugar over the past two to three months, given as a percentage or in mmol/mol. 6.5% (48 mmol/mol) or more is the usual threshold for diabetes, normally confirmed by a second test.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Autoimmune disease
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Immunosuppression
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
BMI (body mass index)
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Following standard non-surgical endodontic retreatment instrumentation, participants received final intracanal irrigation with sterile saline (0.9% NaCl) cooled to 2.5°C, 20 mL, over 5 minutes, in a single visit.
Procedure: Intracanal cryotherapy
Following the same standard non-surgical endodontic retreatment instrumentation, participants received final intracanal irrigation with sterile saline (0.9% NaCl) at room temperature (20-22°C), 20 mL, over 5 minutes, in a single visit.
Procedure: Room-temperature saline irrigation
Final intracanal irrigation with sterile 0.9% saline solution cooled to 2.5°C (using an ice-water bath), 20 mL administered over 5 minutes, performed after canal instrumentation during single-visit non-surgical endodontic retreatment.
Also known as: Cold Saline Irrigation
Final intracanal irrigation with sterile 0.9% saline solution at room temperature (20-22°C), 20 mL administered over 5 minutes, performed after canal instrumentation during single-visit non-surgical endodontic retreatment - identical protocol to the cryotherapy group except for irrigant temperature.
Postoperative pain intensity (VAS score)
Postoperative pain intensity assessed using a Visual Analog Scale (VAS, 0-100 mm, where 0 = no pain and 100 = worst imaginable pain), self-reported by patients. The 24-hour time point is designated as the primary comparison between the cryotherapy and control groups.
Time frame: Baseline, then at 6, 12, 24, 48, and 72 hours and on Day 7 postoperatively (primary comparison at 24 hours)
Salivary nerve growth factor (NGF) levels
Salivary NGF concentration measured by ELISA to assess the neurotrophic/inflammatory biomarker response between cryotherapy and control groups.
Time frame: Baseline (T0), 24 hours (T1), and 72 hours (T2) postoperatively
Gingival crevicular fluid (GCF) prostaglandin E2 (PGE2) levels
PGE2 concentration in gingival crevicular fluid measured by ELISA to assess the inflammatory biomarker response between cryotherapy and control groups.
Time frame: Baseline (T0), 24 hours (T1), and 72 hours (T2) postoperatively
Rescue analgesic (paracetamol) consumption
Number of rescue analgesic (paracetamol 500 mg, oral) tablets consumed by patients as needed over the follow-up period, compared between groups.
Time frame: Over 7 days postoperatively
Total rescue analgesic dose consumed
Total cumulative dose of rescue analgesic (paracetamol, oral, as needed) consumed by patients, expressed in milligrams, compared between groups.
Time frame: Over 7 days postoperatively
Plan to share: No — Individual participant data will not be shared outside the research team due to participant confidentiality commitments outlined in the informed consent process. Biological samples (saliva and gingival crevicular fluid) and associated data are used solely for this study's biomarker analyses (PGE2, NGF via ELISA), are not banked for future research, and will be destroyed 5 years after study completion in accordance with data protection regulations (Turkish Law No. 6698 on the Protection of Personal Data, KVKK). Aggregate, de-identified results will be reported in accordance with CONSORT 2010 guidelines and made available through the study's publication(s).
From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
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Alanya Alaaddin Keykubat University