Antimicrobial and Anti-inflammatory Effects of Simvastatin as an Intracanal Medication

November 20, 2025 updated by: Hadeer Maher Mostafa Mohamed

Antimicrobial and Anti-inflammatory Effects of Simvastatin as an Intracanal Medication in Endodontically Retreated Teeth With Periapical Radiolucency, Randomized Controlled Clinical Trial

Successful endodontic treatment and a predictable outcome can only be achieved by effective root canal debridement, irrigation, and elimination of microorganisms .

The outcome of endodontic treatment performed in controlled clinical environment has demonstrated success rate around 90%.

In certain cases, endodontic treatment may fail, one of the most common reasons is inability to eliminate microorganisms from the root canal. When non-surgical root canal therapy fails, the treatment options include orthograde re-treatment, periradicular surgery, or extraction.

Simvastatin (SIM) is a drug used primarily to treat hyperlipidemia and protect against cardiovascular diseases. It has been shown to possess pleiotropic effects such as antimicrobial, anti-inflammatory, immunomodulatory, antioxidant, and bone-forming properties .

The side chain of this material has a single methyl group. It inhibits hydroxymethyl glutarylcoenzyme reductase that prevents endogenous cholesterol synthesis

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

It has been reported that the inflamed/infected periodontal/endodontic content influence cytokines release . These inflammatory mediators, such as interleukin (IL)-1β, tumor necrosis factor α (TNF-α), and prostaglandin E2 (PGE2), have been detected in periapical tissues and root canal exudates .

Proinflammatory cytokines are able to stimulate, either directly or indirectly, the release of matrix metalloproteinases (MMPs) in the periapical/periodontal region, maintaining a persistent inflammatory process. MMPs are deeply involved in the pathogenesis of pulp, periodontal, and periapical tissue destruction.

As a Gram-positive, facultative anaerobe, Enterococcus Faecalis (E. Faecalis) can survive root canal treatment . It can form biofilms and survive prolonged periods of nutritional deprivation. It can also resist acidic and basic conditions and is hard to eradicate .

E. Faecalis is responsible for 20-70% of endodontic failures and secondary endodontic infections . Due to biofilm development and the organism's physicochemical characteristics, which enable it to alter the prevailing environmental and nutritional conditions, it can even thrive in constrained environments .

Accumulated evidence indicates that the tissue destruction in endodontic and periodontal infections is due to host-derived cytokines induced by lipopolysaccharides (LPS/endotoxins), acting as the major components of the outer leaflet of the outer membrane of gram-negative bacteria.

Calcium hydroxide (Ca (OH)2) has been widely used as an intracanal medicament for retreatment of such failed cases, due to its high pH, its ability to stimulate mineralization, its antibacterial properties, and its tissue-dissolving capability .

Hydroxyl ions create free radicals that destroy components of bacterial cell membranes. These free radicals react with bacterial DNA inhibiting DNA replication and cell activity, and cause mutations. Also, the alkaline pH of calcium hydroxide alters enzyme activity, disrupting cellular metabolism and structural proteins .

Simvastatin enhances alkaline phosphatase activity and mineralization and increases the expression of bone sialoprotein, osteocalcin, and type I collagen, and it is shown to have an anti-inflammatory effect by decreasing the production of interleukin-6 and interleukin-8. SIM is reported to stimulate vascular endothelial growth factor (VEGF) release in a dose dependent manner, and the authors of a previous study suggested that statins may promote osteoblast differentiation and bone nodule formation by stimulating VEGF expression in bone tissue.

Simvastatin is also a renowned safe and affordable medication. It is a novel medicinal substance that is still undergoing dental research . Various animal and clinical studies showed that SIM assists in bone regeneration as well as the anti-inflammatory effect when delivered or applied locally.

Periapical radiography is an essential resource in endodontic diagnosis because it offers important evidence on the progression, regression, and persistence of apical periodontitis (AP) . It is known that periapical radiolucency might not be visible radiographically, although they exist clinically. Conventional radiographs used for the management of endodontic problems yield limited information because of the two-dimensional (2D) nature of the images produced, geometric distortion and anatomical noise.

Study Type

Interventional

Enrollment (Estimated)

54

Phase

  • Not Applicable

Contacts and Locations

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

Study Contact

Study Contact Backup

Study Locations

  • Egypt
      • Cairo, Egypt
        • Recruiting
        • Faculty of Dental Medicine for Girls, Al-Azhar University
        • Contact:

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:

  • Patients had anon contributory medical history.
  • Patients of age categories between 20 to 40 years old, with no physical disability or psychological problems.
  • Single rooted teeth with type I root canal anatomy.
  • Symptomatic cases of failed endodontic treatment with radiographic evidence of periapical bone loss, and the lesion size ranging from 2mm up to 8mm.

Exclusion Criteria:

  • Patients with known sensitivity to the pharmaceutical used in this trial
  • Patients with former endodontic mishaps (as ledges, transportations, perforations or separated instruments)
  • Non restorable teeth
  • Presence of an associated sinus tract.
  • Advanced periodontal involvement
  • Teeth representing root fracture.
  • Pregnant women

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: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Simvastatin Group
About 27 Patients will take Simvastatin 10mg tablets which will be crushed into fine particles and dissolved to prepare an intracanal medication with specific concentration according to the antimicrobial sensitivity study.
Procedure: Simvastatin as an intracanal medication
to evaluate the antimicrobial and anti-inflammatory effects of Simvastatin as an intracanal medication in endodontic retreatment of single rooted teeth with periapical radiolucency.
Other Names:
  • calcium hydroxide intracanal medication
Active Comparator: Calcium hydroxide
About 27 Patients will be injected by Calcium hydroxide intracanal medication in endodontic retreatment of single rooted teeth with periapical radiolucency.
Procedure: Simvastatin as an intracanal medication
to evaluate the antimicrobial and anti-inflammatory effects of Simvastatin as an intracanal medication in endodontic retreatment of single rooted teeth with periapical radiolucency.
Other Names:
  • calcium hydroxide intracanal medication

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Simvastatin antimicrobial effect
Time Frame: 6 Months
Following the treatment, patients will be asked to evaluate The antimicrobial effect of Simvastatin intracanal medication
6 Months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Simvastatin anti-inflammatory effect
Time Frame: 6 Months
Following the treatment, patients will be asked to evaluate The anti-inflammatory effect of Simvastatin intracanal medication and periapical radiolucency healing.
6 Months

Collaborators and Investigators

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

Sponsor

Hadeer Maher Mostafa Mohamed

Investigators

  • Study Chair: Mervat Ibrahim Fawzy, Professor, Faculty of Dental Medicine for Girls Al Azhar University

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)

August 10, 2025

Primary Completion (Estimated)

August 1, 2026

Study Completion (Estimated)

August 10, 2026

Study Registration Dates

First Submitted

November 20, 2025

First Submitted That Met QC Criteria

November 20, 2025

First Posted (Actual)

December 1, 2025

Study Record Updates

Last Update Posted (Actual)

December 1, 2025

Last Update Submitted That Met QC Criteria

November 20, 2025

Last Verified

August 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Effects of Simvastatin

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

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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