Chronic Apical PeriodontitisPhase 4RANKL/OPGNCT07683520
Adjunctive Oral Probiotics in Endodontic Retreatment: Effects on Postoperative Pain and RANKL/OPG Levels
A Phase 4 study testing Linex Adult®, Ca(OH)2 as intracanal medicament and propolis intracanal medication in people with Chronic Apical Periodontitis, run by Ain Shams University at 1 site in Egypt.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Chronic Apical Periodontitis
- What is being tested?
- Linex Adult®, Ca(OH)2 as intracanal medicament and propolis intracanal medication
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 72 participants
- Where
- 1 siteEgypt
- Study dates
- 4 Oct 2025to 20 Jun 2026
- Phase
- Phase 4
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
Egypt1 site
Faculty of Dentistry, Ain Shams University
Cairo, Cairo Governorate, 11566
About this study
Official title: 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
Read the 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.
- Conditions
- Chronic Apical Periodontitis
- Being tested
- Linex Adult®, Ca(OH)2 as intracanal medicament, Placebo, propolis intracanal medication, Empty canal
- Keywords
- RANKL, OPG, Probiotics, Ca(OH)2, Propolis, Postoperative pain, retreatment
- Medical subject headings
- Pain, Postoperative
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Linex Adult®Dietary supplement
Also called Lactobacillus acidophilus, Bifidobacterium animalis
Linex Adult® is an oral probiotic formulation containing Lactobacillus acidophilus, Bifidobacterium animalis, It is administered as one capsule once daily for 21 days.
Ca(OH)2 as intracanal medicamentDrug
Also called Metapaste
Intracanal medication kept for 21 days
PlaceboOther
Also called Matching placebo
Placebo capsule for 21 days
propolis intracanal medicationDrug
Also called Intracanal propolis medicament
Intracanal medication kept for 21 days
Empty canalOther
Also called No intracanal medicament
Empty canal for 21 days
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: 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 Receives: 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 Receives: 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. Receives: Other: Placebo; Other: Empty canal |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: (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.
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.
Measured: 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.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Jul 2026
- Study start4 Oct 2025
- Primary completion4 Jun 2026
- Study completion20 Jun 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Chronic Apical PeriodontitisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 72 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ain Shams University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Amina Mamdouh Badawy, Ain Shams University
- Investigators
- Abeer A.Elhakim El Gendy, PHD, Professor of Endodontics, Study director, Ainshams university
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07683520
- Sponsor's protocol ID
- END 20-15 P
- Acronym
- RANKL/OPG
- Status last verified
- Jul 2026
- First submitted
- 26 Jun 2026
- Last updated
- 6 Jul 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 32436602