Effect of Quercetin in Treatment of Periodontitis

Study Overview
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Brief Summary
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Periodontitis is an immune-inflammatory disease affecting the supporting structures of the teeth. It is a disease of multifactorial etiology, with microbial, genetic, environmental and host factors involved, with the release of oxygen-free radicals by the inflammatory cells. Quercetin, have shown potential antimicrobial activity, lowering of inflammatory markers, cholesterol reduction and inhibiting bone loss. However, this data has largely been obtained from in vitro and animal studies, but data from human studies are limited.

Detailed Description
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Quercetin has been found to decrease the extracellular matrix degradation, promote wound healing when tested in gingival fibroblasts, and showed excellent antibacterial properties. It also possesses antioxidant effect which can be explored to restrict the inflammation in periodontitis. Despite the beneficial effects of Quercetin, its poor aqueous solubility and poor bioavailability result in limited absorption, so scientists have worked on improving the bioavailability of Quercetin using various approaches, such as nanosuspension , self-nano emulsifying systems , microemulsion , solid lipid nanoparticles and cyclodextrin complexes. The combination of oils and emulsifiers enhances the absorption of Quercetin. Hence, nanoemulsion could be a suitable drug delivery vehicle for the loading of Quercetin. Nanoemulsions are more beneficial than microemulsions, as they have high kinetic stability and a smaller droplet size. Therefore, the present study will investigate the efficacy of nanoemulgel of quercetin as adjunct to conventional therapy in treatment of periodontitis.

Official Title
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Efficacy of Quercetin Nanoemulgel as Adjunct Local Delivery Drug in Non-surgical Treatment of Periodontitis

Conditions
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Inflammation Gum

Intervention / Treatment
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* Drug: Quercetin
* Device: scaling and root planing


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Inclusion criteria: Patients with periodontitis stage ( Ⅰ & Ⅱ ). Stage I have CAL 1 to 2mm with no tooth loss and probing depth ≤4 mm. Stage II have CAL 3 to 4mm with no tooth loss and probing depth ≤5 mm.. Patients who have teeth with both mesial and distal neighboring teeth . Patient with more than 20 natural teeth . Patient free from any systemic disease that may effect the periodontal status according to the criteria of Cornell Medical Index and its modification. Exclusion Criteria: Long-term therapy with medications within a month prior to enrollment that could affect periodontal status or healing. Pregnant woman and lactating mothers . Patients with a history of traumatic occlusion. Teeth with both endo-perio lesion . Patients with previous periodontal treatment including scaling and root planing and periodontal surgery in the last 3 and 6 months, respectively .

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Group(I): 10 sites will receive non-surgical periodontal therapy (scaling and root planing) . Group(Ⅱ): 10 sites will receive non-surgical periodontal therapy followed by the application of quercetin nanoemulgel local delivery 2 times one at the day of non-surgical periodontal therapy and after 2 weeks.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Group(I):scaling and root planing only<br>10 sites will receive non-surgical periodontal therapy (scaling and root planing) . | Device: scaling and root planing<br>* - Full-mouth scaling and root planing was performed in 1-2 sessions within 2 weeks using manual scalers and curettes or ultrasonic scaler and local anesthesia was used in case of need for patient comfort.<br>|
| Active Comparator: Group(Ⅱ):scaling and root planing with application of quercetin nanoemulgel<br>10 sites will receive non-surgical periodontal therapy followed by the application of quercetin nanoemulgel local delivery 2 times one at the day of non-surgical periodontal therapy and after 2 weeks. | Drug: Quercetin<br>* Intra-pocket application of quercetin nanoemulgel : After conventional periodontal treatment, the teeth were isolated by cotton rolls for intra pocket application of the gel. That gel was injected in periodontal pocket using syringe with blunt cannula till the gel excess exit from the pocket .<br>Device: scaling and root planing<br>* - Full-mouth scaling and root planing was performed in 1-2 sessions within 2 weeks using manual scalers and curettes or ultrasonic scaler and local anesthesia was used in case of need for patient comfort.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of the changes in the clinical attachment loss | Attachment level was measured using UNC15(University of North Carolina) periodontal probe. Clinical attachment loss was measured as the distance from the cemento-enamel junction to the base of the pocket. | at base line, 1 month and 3 months after treatment | 
| Probing depth | The measurement were recorded by UNC15(University of North Carolina) periodontal probe . Pocket depth was measured as the distances from the free gingival margin to the base of the periodontal pocket. | at base line, 1 month and 3 months after treatment | 
| interferon IFN-γ analysis | The samples were assayed for (IFN-γ) levels using commercially available enzyme-linked immune-sorbent assay (ELISA) . Highly sensitive ELISA kit was used to detect the (IFN-γ) level in pg/ml in the sample of GCF according to the manufacturer's instructions. | at base line, 1 month and 3 months after treatment | 
| reactive oxygen species (ROS) | The samples were assayed for antioxidant effect of quercetin using commercially available reactive oxygen species( ROS) kit . Highly sensitive ROS kit was used according to the manufacturer's instruction | at base line, 1 month and 3 months after treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plaque index (PI) | It used to assess plaque accumulation around gingival margin. The degree of plaque accumulation was recorded as follow: 0= No plaque around the gingival margin. 1= A thin film of plaque around the gingival margin. The plaque may be recognized only by running a probe across the tooth surface. 2= Moderate accumulation of soft deposits on the gingival margin and/or adjacent tooth surface, which can be seen by naked eye. 3= Abundance plaque accumulation within the gingival pocket and/or on the gingival margin and adjacent tooth surface and hard deposits on the tooth surface are seen. | at base line, 1 month and 3 months after treatment | 
| Gingival index (GI) | It used to assess gingival inflammation. The degree of gingival inflammation was recorded as follow: 0 = Normal gingiva. 1 = Mild inflammation, slight change in color, slight edema and no bleeding on probing. 2= Moderate inflammation, redness, edema and bleeding on probing. 3= Severe inflammation, marked redness, edema and tendency to spontaneous bleeding. | at base line, 1 month and 3 months after treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Periodontitis, inflammation, Quarcetin, Nanoemulgel