Cryotherapy and Intracanal Medicaments for Postoperative Pain in Apical Periodontitis

NCT07437612 | Completed Phase 2

• 1 other identifier: BSL5R6DP90
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

This randomized clinical trial aimed to evaluate the effects of intracanal cryotherapy and two intracanal medicaments-calcium hydroxide and metformin-on postoperative spontaneous and percussion pain following root canal treatment in teeth with symptomatic apical periodontitis. In this double-blind, randomized, 2×2 factorial clinical trial, 80 patients with symptomatic apical periodontitis in mandibular premolars were enrolled and randomly assigned to four groups: calcium hydroxide, metformin, cryotherapy plus calcium hydroxide, and cryotherapy plus metformin. All teeth underwent standardized single-visit root canal treatment, and in the cryotherapy groups, final irrigation was performed using sterile saline at 4 °C. Spontaneous pain was assessed preoperatively and daily for 7 postoperative days, while percussion pain was evaluated preoperatively and postoperatively. Pain intensity was recorded using a 100-mm visual analog scale (VAS). Data were analyzed using mixed-effects models for repeated measures and analysis of covariance (ANCOVA) (α = 0.05).

Conditions

Periapical Periodontitis, Chronic Nonsuppurative

Keywords

Periapical Periodontitis; Metformin; Calcium Hydroxide; Intracanal Cryotherapy

Outcome Measures

Primary Outcomes (1)

• Postoperative spontaneous pain

  Assessed using a 100-mm Visual Analog Scale (VAS) A score of 0 represents no pain, while a score of 100 represents the maximum pain. Patients were instructed to document pain levels prior to taking any analgesic medication

  Preoperatively and days 1 to 7

Secondary Outcomes (1)

• Percussion pain

  Preoperatively and postoperative day 7

Study Arms (4)

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

Interventions

Placement of calcium hydroxide as an intracanal medicament DRUG

Calcium hydroxide was applied into the canal after root canal shaping

Calcium Hydroxide

Placement of metformin as an intracanal medicament DRUG

Application of metformin as an intracanal medicament following root canal shaping

Metformin

Application of calcium hydroxide as an intracanal medicament together with intracanal cryotherapy DRUG

Intracanal cryotherapy with 4 °C sterile saline was applied after root canal shaping and before calcium hydroxide placement.

Intracanal Cryotherapy and Calcium Hydroxide

Application of metformin into the canal together with intracanal cryotherapy DRUG

Intracanal cryotherapy with 4 °C sterile saline was applied after root canal shaping and before metformin placement.

Intracanal Cryotherapy and Metformin

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• systemically healthy
• Mandibular premolar teeth diagnosed with pulpal necrosis and indicated for root canal treatment.
• Periapical index score between 0 and 2.
• Aged between 18 and 70 years.
• Able to understand and complete visual analog scale (VAS) assessments.
• Provided written informed consent.

You may not qualify if:

• 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 depths 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.

Sponsors & Collaborators

• Celalettin Topbaş: lead

Study Sites (1)

Saglik Bilimleri University

Istanbul, Turkey (Türkiye)

Location

Related Publications (1)

• Tan Y, Chen J, Jiang Y, Chen X, Li J, Chen B, Gao J. The anti-periodontitis action of metformin via targeting the NLRP3 inflammasome. Arch Oral Biol 2020;114:104692. doi:10.1016/j.archoralbio.2020.104692

  BACKGROUND

MeSH Terms

Conditions

Periapical Granuloma; Periapical Periodontitis

Condition Hierarchy (Ancestors)

Periapical Diseases; Jaw Diseases; Stomatognathic Diseases; Periodontal Diseases; Mouth Diseases; Periodontitis

Study Officials

• Ali O ILHAN, dds

  Saglik Bilimleri University

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: CARE PROVIDER
• Masking Details: The treating clinician was blinded to the type of intracanal medicament and method until the final stage of the procedure. The previously randomized treatment protocol was disclosed to the clinician by an assistant.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: ASSOCIATE PROFESSOR

Model Details: In this double-blind, 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 received standardized single-visit root canal treatment.

Study Record Dates

• First Submitted: January 30, 2026
• First Posted: February 27, 2026
• Study Start: February 13, 2023
• Primary Completion: January 1, 2024
• Study Completion: January 1, 2024
• Last Updated: February 27, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

TU (1)