Adjunctive Oral Probiotics in Endodontic Retreatment: Effects on Postoperative Pain and RANKL/OPG Levels (RANKL/OPG)

July 1, 2026 updated by: Amina Mamdouh Badawy, Ain Shams University

The Effect of Systemic Administration of Probiotics and Intra-Canal Medications on Level of Nuclear Factor Kappa B Ligand, Osteoprotegerin and Postoperative Pain in Patients With Chronic Apical Periodontitis: (Randomized Controlled Clinical Trial)

This study aimed to evaluate the effect of oral administration of probiotics as an adjunctive treatment to local intracanal medicaments, namely propolis and calcium hydroxide or empty canal, on the levels of receptor activator of nuclear factor kappa B ligand (RANKL) and osteoprotegerin (OPG), as well as on postoperative pain following root canal retreatment of teeth with chronic apical periodontitis

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Post-treatment chronic apical periodontitis is an inflammatory condition caused by persistent microbial infection within the root canal system, characterized by progressive periapical bone destruction mediated by host immune-inflammatory mechanisms. Root canal retreatment remains the treatment of choice for failed endodontic cases; however, postoperative pain and incomplete resolution of inflammatory mediators remain common concerns. Clinical evidence demonstrates that postoperative pain following endodontic retreatment is influenced by microbial persistence, host inflammatory response, and intracanal medication protocols.

The RANK/RANKL/OPG axis is a key regulator of osteoclastic activity and periapical bone resorption. Elevated RANKL levels and altered RANKL/OPG ratio are associated with active periapical bone destruction. Modulation of this pathway may improve healing outcomes. Recent studies suggest that probiotics can regulate immune response, reduce inflammatory cytokines, and decrease RANKL expression.

This randomized clinical trial includes patients diagnosed with previously root-filled teeth presenting with chronic apical periodontitis indicated for non-surgical retreatment.

Standardized retreatment procedures are performed under aseptic conditions. Periapical exudate samples collected for biochemical analysis of RANKL and OPG levels at predetermined time points. Postoperative pain is assessed to investigate whether systemic probiotic administration can act as a host-modulating adjunct in endodontic retreatment and improve both symptomatic and biological healing outcomes.

Study Type

Interventional

Enrollment (Actual)

72

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Egypt
    • Cairo Governorate
      • Cairo, Cairo Governorate, Egypt, 11566
        • Faculty of Dentistry, Ain Shams University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Previously treated failed single rooted teeth with chronic apical periodontitis.
  • No use of antibiotic three months before treatment.
  • Patients are free of any systemic disease.
  • Positive patient acceptance for participation

Exclusion Criteria:

  • Teeth that are badly broken down with difficult isolation.
  • Signs of acute infection, root fracture, root surface caries, swellings or ankylosis
  • Periodontally affected teeth with pockets deeper than 4mm.
  • Pregnant or lactating woman.
  • Patients who needs any prophylactic antibiotic.
  • Patients with allergy to pollen.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Oral probiotics + Local Ca(OH)2 ICM
Following endodontic retreatment, calcium hydroxide placed as an intracanal medicament . Participants receive Linex Adult® (oral probiotics: Lactobacillus acidophilus, Bifidobacterium animalis ), one capsule daily for 21 days.
Dietary supplement: Linex Adult®
Linex Adult® is an oral probiotic formulation containing Lactobacillus acidophilus, Bifidobacterium animalis, It is administered as one capsule once daily for 21 days.
Other Names:
  • Lactobacillus acidophilus, Bifidobacterium animalis
Drug: Ca(OH)2 as intracanal medicament
Intracanal medication kept for 21 days
Other Names:
  • Metapaste
Experimental: Oral probiotics + Local Propolis ICM
Following endodontic retreatment, propolis placed as an intracanal medicament. Participants receive Linex Adult® (oral probiotics: Lactobacillus acidophilus, Bifidobacterium animalis), one capsule daily for 21 days.
Dietary supplement: Linex Adult®
Linex Adult® is an oral probiotic formulation containing Lactobacillus acidophilus, Bifidobacterium animalis, It is administered as one capsule once daily for 21 days.
Other Names:
  • Lactobacillus acidophilus, Bifidobacterium animalis
Drug: propolis intracanal medication
Intracanal medication kept for 21 days
Other Names:
  • Intracanal propolis medicament
Experimental: Oral probiotics + Empty canal
Following endodontic retreatment, the canal was left empty without intracanal medicament. Participants received Linex Adult® (oral probiotics: Lactobacillus acidophilus, Bifidobacterium animalis), one capsule daily for 21 days.
Dietary supplement: Linex Adult®
Linex Adult® is an oral probiotic formulation containing Lactobacillus acidophilus, Bifidobacterium animalis, It is administered as one capsule once daily for 21 days.
Other Names:
  • Lactobacillus acidophilus, Bifidobacterium animalis
Other: Empty canal
Empty canal for 21 days
Other Names:
  • No intracanal medicament
Active Comparator: Oral placebo + Local Ca(OH)2 ICM
Following endodontic retreatment, Ca(OH)2 was placed as an intracanal medicament. Participants received placebo, one capsule daily for 21 days
Drug: Ca(OH)2 as intracanal medicament
Intracanal medication kept for 21 days
Other Names:
  • Metapaste
Other: Placebo
Placebo capsule for 21 days
Other Names:
  • Matching placebo
Active Comparator: Oral placebo+ Local propolis ICM
Following endodontic retreatment, propolis was placed as an intracanal medicament. Participants received placebo, one capsule daily for 21 days
Drug: propolis intracanal medication
Intracanal medication kept for 21 days
Other Names:
  • Intracanal propolis medicament
Other: Placebo
Placebo capsule for 21 days
Other Names:
  • Matching placebo
Placebo Comparator: Oral placebo + Empty canal
Following endodontic retreatment, the canal was left empty without intracanal medicament. Participants received Linex Adult® (oral probiotics: Lactobacillus acidophilus, Bifidobacterium animalis), one capsule daily for 21 days.
Other: Empty canal
Empty canal for 21 days
Other Names:
  • No intracanal medicament
Other: Placebo
Placebo capsule for 21 days
Other Names:
  • Matching placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The effect on RANKL and OPG levels in teeth with chronic apical periodontitis.
Time Frame: (S1) measured in the first visit Immediately post-instrumentation and before ICM placement or oral supplement administration. (S2) After 21 days, immediately after removal of ICM and before obturation.
Level of RANKL and OPG measured with periapical samples (S1) and (S2) and analysed using ELISA test
(S1) measured in the first visit Immediately post-instrumentation and before ICM placement or oral supplement administration. (S2) After 21 days, immediately after removal of ICM and before obturation.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The effect on postoperative pain.
Time Frame: Inter-appointment pain: baseline (start of the first visit), 4, 12, 24, 48, and 72 hours, and Week 1 and Week 2 after the first visit. Post-obturation pain: baseline (start of the second visit), 4, 12, 24, 48, and 72 hours after obturation.
Pain level measured using the Numeric Rating Scale (NRS), ranging from 0 (no pain) to 10 (worst possible pain), to evaluate inter-appointment pain between the first and second retreatment visits and post-obturation pain after the second retreatment visit and root canal obturation.
Inter-appointment pain: baseline (start of the first visit), 4, 12, 24, 48, and 72 hours, and Week 1 and Week 2 after the first visit. Post-obturation pain: baseline (start of the second visit), 4, 12, 24, 48, and 72 hours after obturation.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Ain Shams University

Investigators

  • Study Director: Abeer A.Elhakim El Gendy, PHD, Professor of Endodontics, Ainshams university

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 4, 2025

Primary Completion (Actual)

June 4, 2026

Study Completion (Actual)

June 20, 2026

Study Registration Dates

First Submitted

June 26, 2026

First Submitted That Met QC Criteria

July 1, 2026

First Posted (Actual)

July 6, 2026

Study Record Updates

Last Update Posted (Actual)

July 6, 2026

Last Update Submitted That Met QC Criteria

July 1, 2026

Last Verified

July 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • END 20-15 P

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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