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.
Who can participate
Age range
18 Years – 65 Years
Sex
ALL
See this in plain English?
AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.
Inclusion Criteria:
* Age 18-65 years, systemically healthy individuals (ASA I-II)
* Single-rooted mandibular premolar teeth with a previous root canal treatment, requiring non-surgical retreatment due to asymptomatic apical periodontitis
* Presence of periapical radiolucency (Periapical Index \[PAI\] ≥ 3)
* No antibiotic use within the past 1 month
* Willing to participate and has signed the informed consent form
Exclusion Criteria:
* Pregnancy or lactation
* Uncontrolled diabetes mellitus (HbA1c \> 7%), diagnosed autoimmune disease, or receiving immunosuppressive therapy
* Systemic corticosteroid use within the past 3 months
* Body mass index (BMI) greater than 35 kg/m²
* Presence of acute infection (e.g., acute apical abscess or cellulitis)
* Conditions precluding retreatment, including advanced periodontal breakdown (clinical attachment loss \> 5 mm), root resorption, perforation, or advanced canal calcification
* Absence of an opposing (antagonist) tooth resulting in lack of functional occlusal contact
* Diagnosed chronic pain syndrome or currently receiving active psychiatric treatment
* Smoking more than 10 cigarettes per day
* Use of analgesics or NSAIDs within the past 24 hours
* Antibiotic use within the past 1 month
Questions worth asking your doctor
Bring these to your next appointment. They're a starting point for a shared conversation — not a sign you qualify or a recommendation to enrol.
1Based on my diagnosis and history, is this trial worth exploring for me — or is there a standard treatment we should try first?
2What does this trial's phase tell us about how much is already known about its safety and benefit?
3What would taking part actually involve for me — visits, tests, time, and travel?
4What are the known and possible risks or side effects I should weigh, and how would they be monitored?
5If this trial isn't the right fit, what other options or trials would you suggest I look into?
Generated to help you prepare — always confirm anything about your own eligibility and care with the study team and your doctor.
Questions for the trial coordinator
The trial coordinator is the person who runs the study day to day. These cover the practical side — logistics, costs, and what taking part would actually mean for your life. The study team confirms whether you meet the criteria; these are questions to ask, not a sign you qualify.
1What does taking part actually involve week to week — how many visits, where, and how long does each one take?
2What costs are covered by the study, and what might I have to pay for myself, including travel, parking, or time off work?
3What happens during screening, and what happens if the study team confirms I don't meet the criteria after those tests?
4Who pays for the scans, blood work, and other tests the trial requires — the study, my insurance, or me?
5How will being in the trial affect my regular care, and will my own doctor stay informed and involved?
6Can I leave the trial at any point if I change my mind, and what would happen to my care if I do?
A starting point for the conversation — always confirm anything about your own eligibility, costs, and care with the study team and your doctor.
What they're measuring
1
Postoperative pain intensity (VAS score)
Timeframe: Baseline, then at 6, 12, 24, 48, and 72 hours and on Day 7 postoperatively (primary comparison at 24 hours)