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

NCT ID: NCT07256561

Last Updated: 2025-12-01

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 54 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-08-10
• Study Completion Date: 2026-08-10

Brief Summary

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

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.

Conditions

Endodontically Retard Teeth; Periapical Radiolucency

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: ACTIVE_COMPARATOR

Simvastatin as an intracanal medication

Intervention Type: PROCEDURE

to evaluate the antimicrobial and anti-inflammatory effects of Simvastatin as an intracanal medication in endodontic retreatment of single rooted teeth with periapical radiolucency.

Calcium hydroxide

About 27 Patients will be injected by Calcium hydroxide intracanal medication in endodontic retreatment of single rooted teeth with periapical radiolucency.

Group Type: ACTIVE_COMPARATOR

Simvastatin as an intracanal medication

Intervention Type: PROCEDURE

to evaluate the antimicrobial and anti-inflammatory effects of Simvastatin as an intracanal medication in endodontic retreatment of single rooted teeth with periapical radiolucency.

Interventions

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.

Intervention Type: PROCEDURE

Other Intervention Names

calcium hydroxide intracanal medication

Eligibility Criteria

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

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 40 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hadeer Maher Mostafa Mohamed

OTHER_GOV

Sponsor Role: lead

Responsible Party

Hadeer Maher Mostafa Mohamed

Assistant Lecturer of Endodontics at Suez University

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Mervat Ibrahim Fawzy, Professor

Role: STUDY_CHAIR

Faculty of Dental Medicine for Girls Al Azhar University

Locations

Faculty of Dental Medicine for Girls, Al-Azhar University

Cairo, , Egypt

Site Status: RECRUITING

Countries

Egypt

Central Contacts

Hadeer Maher Mostafa Mohamed, MSc

Role: CONTACT

hadeer.maher@den.suezuni.edu.eg

+201024990619

Mervat Ibrahim Fawzy, Professor

Role: CONTACT

mervat_3105@yahoo.com

+201005376344

Facility Contacts

Asmaa Abd El-Hady Mohamed Fahmy, Lecturer

Role: primary

asmaaabdelhady.26@azhar.edu.eg

+201225825960

Other Identifiers

Effects of Simvastatin

Identifier Type: -

Identifier Source: org_study_id