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

NCT07683520 | Completed Phase 4

• 1 other identifier: END 20-15 P
• Study Type: interventional
• Target: 72
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Chronic Apical Periodontitis

Keywords

RANKL; OPG; Probiotics; Ca(OH)2; Propolis; Postoperative pain; retreatment

Outcome Measures

Primary Outcomes (1)

• The effect on RANKL and OPG levels in teeth with chronic apical periodontitis.

  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 Outcomes (1)

• The effect on postoperative pain.

  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.

Study Arms (6)

Oral probiotics + Local Ca(OH)2 ICM

EXPERIMENTAL

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®; Drug: Ca(OH)2 as intracanal medicament

Oral probiotics + Local Propolis ICM

EXPERIMENTAL

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®; Drug: propolis intracanal medication

Oral probiotics + Empty canal

EXPERIMENTAL

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®; Other: Empty canal

Oral placebo + Local Ca(OH)2 ICM

ACTIVE COMPARATOR

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; Other: Placebo

Oral placebo+ Local propolis ICM

ACTIVE COMPARATOR

Following endodontic retreatment, propolis was placed as an intracanal medicament. Participants received placebo, one capsule daily for 21 days

Other: Placebo; Drug: propolis intracanal medication

Oral placebo + Empty canal

PLACEBO COMPARATOR

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: Placebo; Other: Empty canal

Interventions

Linex Adult® DIETARY_SUPPLEMENT

Linex Adult® is an oral probiotic formulation containing Lactobacillus acidophilus, Bifidobacterium animalis, It is administered as one capsule once daily for 21 days.

Also known as: Lactobacillus acidophilus, Bifidobacterium animalis

Oral probiotics + Empty canal; Oral probiotics + Local Ca(OH)2 ICM; Oral probiotics + Local Propolis ICM

Ca(OH)2 as intracanal medicament DRUG

Intracanal medication kept for 21 days

Also known as: Metapaste

Oral placebo + Local Ca(OH)2 ICM; Oral probiotics + Local Ca(OH)2 ICM

Placebo OTHER

Placebo capsule for 21 days

Also known as: Matching placebo

Oral placebo + Empty canal; Oral placebo + Local Ca(OH)2 ICM; Oral placebo+ Local propolis ICM

propolis intracanal medication DRUG

Intracanal medication kept for 21 days

Also known as: Intracanal propolis medicament

Oral placebo+ Local propolis ICM; Oral probiotics + Local Propolis ICM

Empty canal OTHER

Empty canal for 21 days

Also known as: No intracanal medicament

Oral placebo + Empty canal; Oral probiotics + Empty canal

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Ain Shams University: lead

Study Sites (1)

Faculty of Dentistry, Ain Shams University

Cairo, Cairo Governorate, 11566, Egypt

Location

Related Publications (1)

• Cosme-Silva L, Dal-Fabbro R, Cintra LTA, Ervolino E, Plazza F, Mogami Bomfim S, Duarte PCT, Junior VEDS, Gomes-Filho JE. Reduced bone resorption and inflammation in apical periodontitis evoked by dietary supplementation with probiotics in rats. Int Endod J. 2020 Aug;53(8):1084-1092. doi: 10.1111/iej.13311. Epub 2020 May 21.

  PMID: 32436602 BACKGROUND

MeSH Terms

Conditions

Pain, Postoperative

Interventions

Lacteol

Condition Hierarchy (Ancestors)

Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Pain; Neurologic Manifestations; Signs and Symptoms

Study Officials

• Abeer A.Elhakim El Gendy, PHD, Professor of Endodontics

  Ainshams university

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Masking Details: Masking was implemented at the participant and outcomes assessor levels. Randomization and allocation concealment were performed by an independent person not involved in treatment procedures or outcome assessment. For systemic probiotic, the probiotic and placebo capsules were prepared in identical opaque containers, and the allocation key was maintained by the independent allocator until completion of data collection. so, the principal investigator and care provider were blinded regarding probiotic/placebo allocation throughout the intervention period. However, due to the nature of the intracanal medicament intervention (calcium hydroxide or propolis or left empty ), blinding of the principal investigator and care provider was not feasible at the stage of ICM placement. But allocation concealment for the intracanal medicament was maintained using sealed opaque envelopes, which were opened only after completion of all treatment procedures and immediately before placement of the ICM
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Phd candidate

Study Record Dates

• First Submitted: June 26, 2026
• First Posted: July 6, 2026
• Study Start: October 4, 2025
• Primary Completion: June 4, 2026
• Study Completion: June 20, 2026
• Last Updated: July 6, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

EG (1)