Effect of Caffeic Acid Phenethyl Ester as a Matrix Metalloproteinase Inhibitor: Randomized Controlled Clinical Trial

Study Overview
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Brief Summary
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Matrix metalloproteinases (MMPs); activated by the application of adhesive systems on dentin cause degradation of the collagen proteins and loss of bond strength in adhesive restorations. Caffeic acid phenethyl ester (CAPE) showed inhibitory activities on dentinal MMPs. It is hypothesised that dentin pretreatment with CAPE, as an MMP inhibitor, would be beneficial for the bonding of resin material and tooth substrate over the course of time. This study evaluated the effect of 5 % CAPE pretreatment on the microtensile bond strength of a nanohybrid resin restoration applied with total-etch or self-etch adhesive systems on 10 patients (12-18 yrs). Two standard cavities (3 x 3 x 4 mm) prepared on the occlusal surfaces of one of the two premolar teeth in each patient were randomly assigned into four treatment groups (n=10); 5% CAPE pretreatment and total-etch adhesive (TC), Total-etch adhesive (control) (T), 5% CAPE pretreatment and self-etch adhesive (SC), Self-etch adhesive (control) (S) followed by restoration and 3 months of intra-oral functioning. After teeth extraction, the specimens were stored in distilled water+thymol solution at 4°C to inhibit microbial growth and used in one week period. Dentin-composite sticks were obtained from each restoration for µTBS tests and scanning electron microscopy (SEM) evaluation. Failure mode analysis was performed microscopically. Data were analysed statistically using Repeated Measure ANOVA (p < 0.05). Dentin pretreatment with CAPE solution (5%) for 60 seconds significantly increased the composite resin restorations' bond strengths to dentin applied with either total-etch or self-etch adhesive system. Thus it can be used as an MMP inhibitor prior to the the resin restorations. However further long term clinical studies are needed to support the use of CAPE pretreatment along with self-etch and total-etch adhesive systems.

Detailed Description
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The aim of the present study was to evaluate the effect of caffeic acid phenethyl ester (CAPE) pretreatment used as matrix metalloproteinase (MMP) inhibitor on microtensile bond strength (µTBS) of nanohybrid resin restorations applied with total-etch or self-etch adhesive systems. A total of 10 patients aged between 12 and 18 years old (4 males, 6 females, mean age:15) received 40 composite restorations. The patients who had contralateral pairs of caries-free premolars which were planned to be extracted for orthodontic treatment were enrolled in the study. This study was performed with a protocol approved by the Ethical Committee for Clinical Studies, Faculty of Medicine, University of Ege, Izmir, Turkey (04.10.2012; no:12-8/6). The treatments were performed after the informed consents were received both from the parents and the patients. Included teeth were in function and no anomalies were found neither in teeth nor in occlusion. Two standard cavities (3 x 3 x 4 mm) with continuous enamel cavosurface margins were prepared on the occlusal surfaces of each premolar tooth.Totally four cavities in each patient were randomly assigned into four treatment groups (n=10); Group TC: CAPE and total-etch adhesive (Syntac; Ivoclar Vivadent AG), Group T: Total-etch adhesive (control), Group SC: CAPE and self-etch adhesive (AdheSE; Ivoclar Vivadent AG), Group S: Self-etch adhesive (control). All cavities were restored incrementally with a nano-filled hybrid composite resin (Tetric-N-Ceram, Ivoclar Vivadent AG) in which polymerization in each layer was performed for 40 seconds with a light-curing unit (BluePhase Ivoclar Vivadent AG) exceeding an energy output of 500mw/sec.

Official Title
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Professor, Ege University Faculty of Dentistry

Conditions
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Matrix Metalloproteinase Inhibitors, Composite Resins

Intervention / Treatment
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* Drug: total-etch adhesive
* Drug: CAPE-T
* Drug: self-etch adhesive
* Drug: CAPE-S


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria:I Occlusally functioning teeth without any anomalies Good oral hygiene No systemical disorders No periodontal diseases No allergic reactions to the dental materials Exclusion Criteria: Patients not eligible for premolar teeth extraction for orthodontic treatment Poor oral hygiene Non-functioning premolar teeth to be included Patients having systemical disorders, periodontal diseases or allergic reactions to dental materials

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: self-etch adhesive<br>application of self-etch adhesive on cavities. | Drug: self-etch adhesive<br>* comparator use of total-etch adhesive<br>* Other names: adhesive;|
| Experimental: CAPE-S<br>CAPE before self-etch adhesive | Drug: CAPE-S<br>* experimental group<br>* Other names: CAPE solution;|
| Active Comparator: total-etch adhesive<br>total-etch adhesive on cavities. | Drug: total-etch adhesive<br>* comparator use of total-etch adhesive<br>* Other names: adhesive;|
| Experimental: CAPE-T<br>CAPE before total-etch adhesive application | Drug: CAPE-T<br>* experimental group<br>* Other names: CAPE solution;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determination of structural integrity of hybrid layer in forty restorations on 10 patients using scanning electron microscopy after application of different adhesive strategies and a matrix metalloproteinase inhibitor. |  | 2 years |