Topic Simvastatin for Bone Regeneration (SM)

University of Granada (UGR)

Status and phase: Enrolling; Early Phase 1

Conditions: Dimensional Changes; Bone Density

Treatments: Drug: Simvastatin Placebo; Drug: Simvastatin 10 mg; Drug: Simvastatin

Study type: Interventional

Funder types: Other

Identifiers

NCT07031778

3904/CEIH/2023 (Other Identifier)

Details and patient eligibility

About

The goal of this clinical trial is to evaluate the efficacy of topical application of simvastatin in bone regeneration in the maxillae, in the reduction of dimensional bone changes, using mandibular third molar surgery as a model and assessing bone healing at 12 weeks. We will also compare the two forms of intralveolar topical administration currently used to assess which is the best form of administration. The main questions it aims to answer are:

• Can the topical application of simvastatin, used as a preservation material, improve the variations with respect to bone dimensions and density that occur after tooth extraction.
• Can topical application of SM improve soft tissue healing.
• Does the topical application of SM produce changes with respect to postoperative variables of pain, inflammation or trismus.
• What is the best vehicle for topical SM administration?

For this purpose, the investigators will randomly place 4 topical treatment options in the postextraction alveoli:

• SM in gel form
• collagen sponge impregnated with saline solution containing 10 mg of SM
• collagen sponge with placebo gel. All patients will undergo postoperative CBCT, which will be repeated at 12 weeks.

In addition, inflammation, trismus and pain variables will be measured preoperatively, at 24 hours, 3 and 7 days.

Full description

The study design is a double-blind randomized clinical trial (RCT). The study population consisted of patients referred to the Master's Degree in Oral Surgery and Implantology of the Faculty of Dentistry of the UGR (Granada) with an indication for surgical extraction of mandibular third molars.

A sample of 90 third molars will be used to establish a confidence level of 95% and a power of 90%. The sample will be divided into 3 groups of 30 each. Group I: 30 mandibular third molars in which gel with 1.2% simvastatin is used for healing. Group II: 30 mandibular third molars in which a collagen sponge impregnated with saline solution containing 10 mg of the active ingredient simvastatin is used for healing. Group III: 30 mandibular third molars in which a collagen sponge impregnated in gel without SM is used for healing.

SURGICAL PROCEDURE:

Extraction will be performed only of included mandibular third molars. For this purpose we will anesthetize the lower dental nerve, lingual nerve and buccal nerve using 4% articaine with epinephrine by means of the truncular technique.

The intervention will be performed by flap lifting, ostectomy with handpiece and round bur, or odontosection with turbine whenever the case requires it. The socket will be curetted and washed with physiological saline solution to ensure that no surgical debris remains. After this, we will proceed to place in the socket the combination of material chosen by randomization (simvastatin gel, gel without simvastatin, collagen sponge with simvastatin or only collagen sponge). Once the filling material has been placed, we will proceed to the primary closure of the wound with 3.0 silk. We will place a gauze with 0.20% chlorhexidine gel at the end of the extraction, for the patient to keep it for 30 minutes. We will indicate to the patient the appropriate postoperative care and we will prescribe 0.12% chlorhexidine mouthwash for rinsing after brushing. One week later, the patient will be seen to remove the suture.

Postoperative medication:

• Antibiotic treatment: amoxicillin 750 mg 1 every 8 hours, for 7 days. In case of allergy to penicillin, the drug of choice will be clindamycin 300 mg 1 every 8 hours.
• Analgesic and anti-inflammatory treatment: ibuprofen 400 mg 1 every 8 hours for two days, from the third day on demand. Rescue paracetamol 1 g.

VARIABLES TO BE STUDIED

Primary Variables:

The primary variable to be studied will be the dimensional changes

Secondary variables:

The secondary variables to be studied will be bone density measured in Hounsfield units , soft tissue healing, pain and analgesia, inflammation and trismus.

Enrollment: 90 estimated patients

Sex: All

Ages: 18 to 40 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Anesthetic risk ASA I-II.
• Patients with the adjacent tooth in the mouth (37 or 47).
• Third molars with fully developed roots.
• Mandibular third molars included or semi-included.
• With indication for extraction.
• Signed informed consent.

Exclusion criteria

• Pregnant or lactating women.
• Chronic smokers.
• Patients with decompensated metabolic disease.
• Patients with motor difficulties that prevent or hinder hygiene.
• Patients who are using statins to treat hypercholesterolemia.
• Patients under treatment with drugs that could affect the osseointegration process such as chemotherapy drugs, bisphosphonates, corticosteroids or immunosuppressants.
• Patients with metabolic bone diseases or who have undergone radiotherapy in the last five years.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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90 participants in 3 patient groups, including a placebo group

drug intervention: Gel SM

Experimental group

Description:

30 lower third molars in whose alveolus post-extraction we will place simvastatin gel at 1.2%.

Treatment:

Drug: Simvastatin

Drug intervention: Sm + collagen sponge

Active Comparator group

Description:

30 lower third molars in whose alveolus post-extraction we will place a collagen sponge impregnated with saline solution containing 10 mg of simvastatin.

Treatment:

Drug: Simvastatin 10 mg

Control

Placebo Comparator group

Description:

30 lower third molars in whose alveolus post-extraction we will place a collagen sponge impregnated with gel without simvastatin

Treatment:

Drug: Simvastatin Placebo