The Assessment of Clinical Efficacy of Topical Application of 5% Thymoquinone Gel for Gingivitis Patients

Study Overview
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Brief Summary
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Gingival diseases occur commonly in the global population and herbal products for its intervention have limited body of research evidence. This study to evaluate the clinical efficacy of 5% thymoquinone (TQ) gel as an adjunct to scaling and root planing (SRP) in patients diagnosed with gingivitis. OBJECTIVE: To evaluate the efficacy of 5% TQ gel using a novel liposome drug delivery as a topical application following SRP in gingivitis patients. DESIGN: Double-blinded, parallel, randomized controlled clinical trial. SETTING: Faculty of Dentistry, King Abdulaziz University, and Qassim University, Saudi Arabia

Detailed Description
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This randomized controlled clinical trial will be conducted to evaluate of clinical efficacy of TQ gel (5%) as an adjunct to SRP in patients with gingivitis (n=63). The patients will be recruited from the Faculty of Dentistry, Qassim University and the subjects will be divided into three groups and include Group I (SRP+TQ gel), Group II (SRP+Placebo), and Group III (Only SRP-one stage prophylaxis). The subjects will be given an explanation of the purpose of the study; informed consent will be obtained in a written format. This clinical trial will be performed in accordance with the ICH (International Conference on Harmonization-E6 'Guideline for Good Clinical Practice') and Helsinki Declaration 1975, as revised in 2000. The study protocol was approved by the Institutional Review Board, Qassim University, Saudi Arabia (IRB No: EAC 104-2018). The complete oral diagnosis will be performed during the screening visit by clinical assessment and periapical radiographs may be indicated to obtain a definitive diagnosis, The periodontal charting will be performed and recorded in the patient's case record. The participants will be consecutively enrolled with the following inclusion and exclusion criteria. Preparation of Lipid-based TQ gel formulation (5%): Thymoquinone extract (Sigma Aldrich extract-Product No:03416) was obtained in crystalline form. Mode of Administration In Group I patients, the lipid-based TQ gel (5%) will be applied topically to the affected areas, twice daily for two weeks following SRP. The investigator will perform the treatment of gingivitis based on the patient's response to therapy. For home care, the patients will be instructed to clean and dry the affected area prior to the gel application and hands to be washed prior to and after its application. The patients would be instructed to not eat for 30 minutes following its application. The same will be done for Group II patients who were treated with SRP followed by a placebo gel application in the affected areas. The Group III patients will be subjected to one-stage oral prophylaxis. It will be a double-blinded clinical trial as the patients would not be made aware of which gel preparation was given to them and the principal investigators would not be aware of the patient's group while performing clinical measurements, whereas the operator performed SRP and gel application. Treatment Compliance A diary card will be given to all the patients along with instructions on filling the card and reminders to bring it on subsequent visits will be mentioned. The principal investigator will ensure that each patient used at least 75% and not more than 125% of the study drug over the course of the study period. The drug accountability i.e., receipt, dispensing, and return of the drug) will be performed either by the principal investigator or his designee. The assessment of the primary endpoint will be based on the clinical scoring conducted on a weekly basis till the end of the study. Clinical Evaluation The clinical parameters such as plaque index (PI) and papillary bleeding index (PBI) will be evaluated for all the patients at the appropriate follow-up intervals. The parameters will be evaluated by two independent examiners. The adverse events, if any with the administration of TQ gel will be monitored and it would be graded as per the intensity as mild, moderate, and severe. Discontinuation of Treatment In case of adverse events with the use of the study drug, the patients would be withdrawn from therapy or clinical assessment. Also, when the patients suffer from significant illness or undergo surgery during the course of the study, they would be withdrawn from the trial. The non-compliant patients who did not adhere to the study protocol or for other justifiable reasons were withdrawn from the current clinical trial.

Official Title
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A Randomized Controlled Clinical Trial for the Assessment of Clinical Efficacy of Topical Application of 5% Thymoquinone Gel for Gingivitis Patients

Conditions
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Gingivitis

Intervention / Treatment
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* Biological: 5% thymoquinone (TQ) gel
* Biological: SRP and placebo
* Procedure: Only SRP-one stage prophylaxis


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: • Patient diagnosed with gingivitis (Probing<3mm with bleeding on probing ≥10% of sites) (Trombelli, Farina et al. 2018) Minimum twenty teeth in the oral cavity Age: 18-40 years Exclusion Criteria: • Patients with systemic diseases that have an association with periodontal diseases like diabetes, cardiovascular diseases, blood dyscrasias, or diseases of immune system and would require antibiotics prior to dental treatment Patients who received antibiotic therapy in the last 3 months prior to the trial Pregnant or lactating females Patients treated with drugs such as antacids, warfarin or cyclosporine Presence of overhanging restorations or other contributing factors to periodontal disease Allergy to Nigella sativa and/or TQ

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: DESIGN: Double-blinded, parallel, randomized controlled clinical trial. SETTING: Faculty of Dentistry, King Abdulaziz University, and Qassim University, Saudi Arabia PARTICIPANTS AND METHODS: This trial will enroll 63 participants with age group between 18-40 years attending the outpatient clinics of Faculty of dentistry, Qassim University, Saudi Arabia with confirmed clinical diagnosis of gingivitis. The enrolled subjects will be categorized in three groups: Group I-TQ gel with SRP, Group II-Placebo with SRP, and Group III-SRP alone and clinical outcomes will be measured at baseline and two-week follow-up visit. MAIN OUTCOME MEASURES: Plaque Index (PI), Papillary Bleeding Index (PBI) and any adverse events with TQ gel categorized as mild, moderate, and severe. SAMPLE SIZE: 63 patients. Group I (n=21); Group II (n=21); Group III (n=21)
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group I (SRP and TQ gel)<br>In Group I patients, the lipid based TQ gel (5%) will be applied topically to the affected areas, twice daily for two weeks following SRP. The investigator performs the treatment of gingivitis based on the patient's response to therapy. For home care, the patients will be instructed to clean and dry the affected area prior to the gel application and hands will be washed prior and after its application. The patients will be instructed to not eat for 30 minutes following its application | Biological: 5% thymoquinone (TQ) gel<br>* Mode of Administration In Group I patients, the lipid based TQ gel (5%) will be applied topically to the affected areas, twice daily for two weeks following SRP. The investigator performing the treatment of gingivitis based on the patient's response to therapy. For home care, the patients will be instructed to clean and dry the affected area prior to the gel application and hands will be washed prior and after its application. The patients will be instructed to not eat for 30 minutes following its application.<br>|
| Placebo Comparator: Group II (SRP and Placebo)<br>In Group II patients, the placebo gel will be applied topically to the affected areas, twice daily for two weeks following SRP. The investigator performs the treatment of gingivitis based on the patient's response to therapy. For home care, the patients will be instructed to clean and dry the affected area prior to the gel application and hands will be washed prior to and after its application. The patients will be instructed to not eat for 30 minutes following its application | Biological: SRP and placebo<br>* In Group II patients, the placebo gel will be applied topically to the affected areas, twice daily for two weeks following SRP. The investigator performs the treatment of gingivitis based on the patient's response to therapy. For home care, the patients will be instructed to clean and dry the affected area prior to the gel application and hands will be washed prior to and after its application. The patients will be instructed to not eat for 30 minutes following its application<br>|
| Active Comparator: Group III (Only SRP and one stage prophylaxis)<br>The Group III patients will be subjected to one-stage oral prophylaxis. | Procedure: Only SRP-one stage prophylaxis<br>* The Group III patients will be subjected to one-stage oral prophylaxis.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plaque index | The measurement of the state of oral hygiene by Silness-Löe plaque index is based on recording both soft debris and mineralized deposits on the following teeth: 0 No plaque A film of plaque adhering to the free gingival margin and adjacent area of the tooth. The plaque may be seen in situ only after application of disclosing solution or by using the probe on the tooth surface. Moderate accumulation of soft deposit s within the gingival pocket, or the tooth and gingival margin which can be seen with the naked eye. Abundance of soft matter within the gingival pocket and/or on the tooth and gingival margin. | 2 weeks | 
| Papillary bleeding index | This index permits both immediate evaluation of the patient's gingival condition and his motivation, based upon the actual bleeding tendency of the gingival papillae. A periodontal probe is inserted into the gingival sulcus at the base of the papilla on the mesial aspect, and then moved coronally to the papilla tip. This is repeated on the distal aspect of the papilla. The intensity of any bleeding is recorded as: Score 0 - no bleeding; Score 1 - A single discreet bleeding point; Score 2 - Several isolated bleeding points or a single line of blood appears; Score 3 - The interdental triangle fills with blood shortly after probing; Score 4 - Profuse bleeding occurs after probing; blood flows immediately into the marginal sulcus. | 2 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with drug related adverse events | Reported during the trial and on clinical assessment | Duration of the clinical trial | 
| Number of participants non compliant/withdraw from the study | Reported during the trial | Duration of the clinical trial | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Gingivitis, THYMOQUINONE, Clinical Trial