Evaluation and comparison of patient reported outcome measures and anti-plaque effectiveness of a novel herbal chewing gum containing neem extracts with placebo chewing gum: A double blind crossover clinical trial.

Background:

Research, both longitudinal and cross-sectional, has consistently shown that the primary culprit behind gingival and periodontal diseases is microbial biofilm and its harmful byproducts. These biofilms release exotoxins and endotoxins, which significantly damage the tooth’s attachment system, leading to the onset of periodontal disease. To combat this, a variety of anti-plaque agents are available on the market to help maintain oral hygiene. Among these, medicated chewing gum stands out as a promising option, offering a convenient method for administering drugs both locally and systemically. Herbal chewing gum is an innovative drug delivery system designed for the local treatment of gingival and periodontal diseases. It contains a gum base infused with active pharmacological ingredients. This gum serves as a vehicle to administer these active compounds, helping to maintain oral hygiene and prevent plaque deposition.

Scientific research shows that chewing gum is beneficial for oral health, particularly for teeth. Sugar-free gum, in particular, offers proven anti-caries benefits, even though its other oral health effects are less well understood. Chewing sugar-free gum stimulates a strong flow of saliva, which brings several dental advantages:

·       The increased saliva flow speeds up the clearance of sugars from the mouth.

·       The high pH and buffering capacity of this saliva help neutralize plaque acidity after consuming sugar.

·       It enhances the re-mineralization of early caries-like lesions, with clinical trials showing a reduced incidence of cavities in children who chew sugar-free gum.

As an additional method of preventing dental disease, chewing gum can be used alongside traditional preventive measures. It offers several competitive advantages over conventional drug delivery systems: Fast onset of action and high bioavailability, Pleasant taste, Higher compliance due to easy and discreet administration without the need for water, Readiness for use, High acceptance by children.

Overall, sugar-free chewing gum presents an appealing and effective way to enhance oral health. The present proposed study highlights the traditional use of neem products for dental hygiene and the successful applications of neem in the dentistry. Although the importance of biofilm-associated infections to human disease is well-recognized, few novel solutions that effectively eliminate biofilms have been developed thus far. However, encouraging data suggest that neem is consistently more effective at prohibiting bacterial growth and at targeting biofilm-grown cells than many other herbal extracts and is, therefore, worth pursuing as a source for drug discovery. Immunomodulatory, anti-bacterial, anti-inflammatory, anti-hyperglycemic, antifungal, antiviral, antioxidant, antimutagenic, and anticarcinogenic qualities of neem leaf and its compounds have been confirmed. Additionally, studies have demonstrated its efficacy in treating persistent gingivitis.

Hence the aim of the present in vitro study is to evaluate and compare the patient reported outcome measures (PROMS) and anti-plaque effectiveness of novel herbal chewing gum containing neem extracts with placebo chewing gum.

OBJECTIVES

1. To evaluate the PROMS and anti-plaque effectiveness of the novel herbal chewing gum containing neem extracts and placebo chewing gum.

2. To compare the PROMS and anti-plaque effectiveness of the novel herbal chewing gum containing neem extracts and placebo chewing gum.

REVIEW OF LITERATURE

1. Lakshmi et al in 2014 performed a double-blind, crossover clinical trial formulated a chewing gum with chlorhexidine and chitosan to prove its antibacterial and antiplaque properties at low chlorhexidine doses on 18 adult volunteers. The results showed antiplaque activity in the optimized formulation with chitosan and chlorhexidine significantly reduced bacterial counts and improved the gingival index, demonstrating that combining chlorhexidine with chitosan enhances antibacterial effects.

2. Kaur et al. in 2020. assessed the effectiveness of a herbal tooth paste formulation in the reduction of plaque and gingival inflammation in 30 participants. At the end of the study, there was found to be statistically significant reduction in the gingival index, plaque index and papilla bleeding index scores in the subjects in comparison to baseline when the herbal toothpaste was used.

3. Sugiarta et al. in 2019 evaluated the effect of a toothpaste containing neem leaves extract against gingivitis on 40 patients and found significant reduction in PI and PBI Scores on day 7. They concluded that neem leaf extracts are effective in reducing gingivitis.

4. Singh et al. in 2019 performed a randomized controlled trail on 60 subjects to envisage the anti-plaque and anti-inflammatory properties of topical application of neem in the form of a mouth gel.  They compared the topical application of Neem gel with gold standard 0.2% chlorhexidine gel. The GI, PI and SBI decrease significantly in both the groups at 2nd and 3rd week. However, the results were more pronounced in chlorhexidine group. They concluded that chlorhexidine gluconate as well as neem gel can be effectively used as an adjunct to mechanical plaque control in prevention of plaque and gingivitis.

5. Ajay Bhambal et al. in 2011 performed a single blind, randomized cross-over study to assess the effect of neem stick and toothbrush on plaque removal and gingival health among 30 patients. Quigley-Hein plaque and Loe-Silness gingival index were taken at baseline and again following 3 weeks use of either neemstick or toothbrush. Professional tooth cleaning was done 7 days before the start of study and repeated after a further 3 weeks. No significant difference was found between toothbrush and neemstick. But, both resulted in significant reduction in plaque and gingival scores compared to baseline.

MATERIALS AND METHODS

The study will be carried out after obtaining Ethical approval from the institutional ethical committee**.**

Study Design

This will be double blind, crossover clinical trial.

Study Area:

The present study will be conducted at Department of Periodontics and Implant Dentistry, Ranjeet Deshmukh Dental College and Research Centre, Nagpur.

Inclusion criteria

1. Patients agreeing to comply with study protocol and instructions

2. Patients in good health in age range of 18-45 years.

3. Subject should have at least 20 natural permanent teeth in dentition

4. Periodontal pockets not greater than 3mm.

5. All subjects who are deemed medically fit.

6. Subjects having Gingival index score not more than 1.9.

7. Subjects who had a plaque index of greater than 2 at baseline.

Exclusion criteria

1. Smokers and tobacco chewer

2. Patients with systemic diseases or compromising medical condition.

3. Patients on antibiotics one months prior to treatment.

4. Patients using orthodontic appliances either fixed or removable

5. Patients who have been using any mouth rinse containing chemical agents in previous 3 months.

6. Patients allergic or sensitive to any medication.

7. History of any surgical procedure in the selected area in the past six months.

8. Pregnant and lactating women, smokers, acute myocardial infarction within the past 6 months, use of pacemaker and uncontrolled metabolic diseases.

Methodology

The effect on plaque growth of the herbal chewing gum containing neem extracts will be assessed with 60 adult volunteers equally divided into two groups. The clinical parameters will be assessed at the baseline (first visit) and referred to as READING 1.

INTERVENTION 1 IN GROUP 1

The volunteers will be counselled not to brush for the next three days. They will be given the placebo chewing gum and will be instructed about the usage of the chewing gum. On the 3rd day the patients will be called for recording of the clinical parameters referred to as READING 2.

INTERVENTION 2: WASHOUT PERIOD

After this initial period of 3 days, a washout period of another 3 days will be followed and the patients will be instructed to continue their regular brushing and oral hygiene practices and not to use any chewing gum or other chemical plaque control agents. The clinical parameters will be recorded on the 6th day i.e. the end of the washout period. This will be referred to as READING 3.

INTERVENTION 3

Following this washout period week again the patients will be refrained from brushing their teeth for three days. The patients will be asked to use the novel herbal chewing gum with the same protocol as in INTERVENTION 1. Clinical parameters will be recorded on third day i.e. 9th day from baseline and referred to as READING 4.

Similar interventions will be done in group 2 initiating with the use of Novel herbal chewing gum followed by washout period and subsequently use of placebo chewing gum.

Clinical Parameters

The study population will be visually examined for presence or absence of gingival erythema, gingival edema, gingival bleeding and stain indices. The index teeth will be stained for plaque using two tone disclosing solution and cotton swab. The amount of plaque will be scored using the Turesky-Gilmore-Glickman modification of the Quigley Hein plaque index (1970) Gingival inflammation will be recorded using the Gingival Index(GI) by Loe and Silness (1963) and the sulcus bleeding index (SBI) will also be recorded. The patient satisfaction, usability, acceptance, and quality outcomes will be assessed using a novel pre-validated questionnaire.

Administration of Chewing Gum

The patients will be provided with individual packets of chewing gum labeled with his/her name, group of study along with verbal and written instructions of their use (time of use etc.). The patients will be instructed to chew one piece of gum at a time, twice a day, after lunch and after dinner. The chewing time will be set as 10 min each time. The patients will be instructed to avoid use of mouth rinses, tooth pastes, other gum products, candies and avoided eating and drinking up to 1 h of post-commencement of the gum. On every follow up appointment the patient will be checked for any undesirable /side effects.