Efficacy of Locally Delivered Tea Tree Oil Gel as an Adjunct to Non-Surgical Periodontal Management
Condition: Periodontal Pocket
MeSH terms: Periodontal Pocket
Study type: Interventional

Summary: 
      Periodontitis is an inflammatory disease of the teeth's supporting tissues caused by specific
      microbes or groups of microorganisms that contributes to gradual deterioration of the
      periodontal ligament and alveolar bone, leading to periodontal pockets, gingival recession,
      or both. Periodontitis is generally known to be caused by the continuous destruction of the
      surrounding periodontium by complexly organized bacterial communities that colonizes the
      tooth surface, gingival margin, and subgingival area in the form of dental plaque biofilm.
      Researchers suggest the dependence of the treatment of periodontal disease on controlling the
      residual mass of periodontal microbes. Therefore, it is proposed that non-surgical therapy is
      regarded as the initial treatment of periodontitis, which includes mechanical therapy, such
      as oral hygiene measures and mechanical debridement like scaling and root planning. Chemical
      therapy could supplement the non-surgical mechanical therapy, including antimicrobials that
      can be systemically or locally delivered. Systemic delivery of antimicrobials plays a
      critical role in reaching microorganisms dispersed in the oral cavity, including those in
      non-dental oral niches, such as the dorsum of the tongue and crypts of tonsils. Despite these
      advantages, it might lead to unwanted systemic effects -such as nausea, vomiting, and
      gastrointestinal discomfort- or bacterial resistance, as it is completely dependent on the
      patient's adherence. Local Drug Delivery (LDD), compared to systemic administration, provides
      higher therapeutic concentrations of antibiotics at site of infection that is inaccessible to
      the systemic route and it is independent of patient's adherence, as has been shown in various
      studies. Natural products have long been an important source of medications, with natural
      ingredients accounting for almost half of all pharmaceuticals currently in use. Oriental
      medicines have been studied for their antibacterial and anti-inflammatory properties, as well
      as periodontal tissue regeneration, in the treatment of periodontal disease. Tea tree oil
      (TTO), which is an example of one of these natural products, is obtained from paper bark tea
      tree. Tea tree oil was made from natural bush stands of plants, allegedly Melaleuca
      alternifolia, that generated oil with the required chemotype during that early stage.
      Melaleuca alternifolia's native habitat is low-lying, swampy, subtropical coastal ground
      along the Clarence and Richmond Rivers in northeastern New South Wales and southern
      Queensland, and it does not occur natively beyond Australia, unlike numerous other Melaleuca
      species. Tea tree oil, commonly known as "oil of the Tea tree" or "Melaleuca essential oil,"
      is one of the most well-known essential oils. It's made from the Melaleuca alternifolia
      tree's leaves, which have been distilled. This plant is a member of the Myrtaceae family,
      which includes Australian arboreal plants. It is known as "nature's most versatile healer"
      among the native populations. Tea tree oil (TTO) possesses antibacterial, anti-inflammatory,
      antifungal, antiviral, antioxidant, and antiprotozoal properties. Components of tea tree oil
      include: Terpinen-4-ol, α-Terpinene, γ -Terpinene, 1,8-Cineole, α -Terpinolene, p-Cymene,
      (+)-α-Pinene, α -Terpineol, Aromadendrene, δ -Cadinene, (+)-Limonene, Sabinene, and Globulol.
      The capacity of TTO components to reduce the production of TNF α, IL-1beta, IL-8, IL-10, and
      PGE2 by lipopolysaccharide activated human monocytes shows TTO's anti-inflammatory action,
      according to the researchers. TTO's major active components are 1,8-cineole and
      Terpinen-4-ol, and it has been shown that 1,8-cineole possesses anti-inflammatory
      characteristics and may permeate human skin. Other research suggests that Terpinen-4-ol not
      only has anti-inflammatory characteristics like 1,8-cineol, but also has anti-bacterial
      capabilities. TTO has the same antibacterial effect as chlorhexidine (CHX), however the mode
      of action is different. Antibacterial, antiviral, and antifungal activities are all present.
      According to researches, TTO is capable of lowering both inflammatory mediators and
      periodontal pathogens, which in turn reduces the stimulation of inflammatory cytokines,
      allowing periodontal tissues to repair when applied locally in periodontal pockets. Melaleuca
      Alternifolia was chosen for this study as a local drug delivery in the gel form to be placed
      in periodontal pockets as an adjunct to non-surgical periodontal debridement for the
      management of localized periodontitis due to its therapeutic effects, ease of availability of
      tea tree oil, cost effectiveness, and safety with no adverse reactions.
    

Detailed description: 
      Aim & objectives of the Study:

      The aim of this randomized controlled clinical and biochemical trial is to assess the
      efficacy of locally applied Melaleuca Alternifolia (tea tree oil) gel as a supplement to
      non-surgical periodontal debridement in the treatment of patients with localized
      periodontitis.

      Primary objectives:

        -  Assess the effectiveness of tea tree oil gel in the management of periodontitis using
           clinical parameters.

        -  Evaluate Patients' satisfaction using the patient satisfaction questionnaire.

      Secondary objective:

      • Determine the impact of tea tree oil gel on the level of Tumor Necrosis Factor (TNF-α) in
      the gingival crevicular fluid.

      Treatment protocol and intervention:

        -  Preoperative periapical radiographs will be done initially to determine the level of
           bone using a standard periapical parallel technique with digital sensor.

        -  The patients will undergo full mouth one stage debridement using ultrasonic scalers,
           manual scalers and curettes.

        -  Full mouth periodontal charting and samples from gingival crevicular fluid will be
           obtained using a sterile perio-paper inserted into the deepest periodontal pocket with
           horizontal bone loss immediately after finishing phase I therapy.

        -  Melaleuca Alternifolia Gel will be gently administered in the deepest pocket by syringe
           with blunt tip and the syringe will be removed slowly to avoid injuring the tissues for
           group I patients after phase 1 therapy by two weeks.

        -  After 3 months of phase I therapy, the patients will be followed up with evaluation of
           the clinical parameters.

      Social & scientific values: Provide the dentists a more convenient way to reduce periodontal
      pockets in periodontitis patient by locally applying Melaleuca Alternifolia gel as an adjunct
      to non-surgical periodontal debridement.

      Risks to study participants: The participants are not subjected to any risks.

      Benefits to study participants:

      Since the main objective of the research is using tea tree oil as a local delivery drug in
      the gel form to be placed in periodontal pockets as an adjunct to non-surgical periodontal
      debridement for the management of localized periodontitis, the benefit of the research is to
      provide the patient better therapeutic effect and a safe local delivery drug with no adverse
      reactions.

      Benefits of the study to the community: Determination of the impact of tea tree oil gel on
      the level of Tumor necrosis factor-alpha (TNF-α) in the gingival crevicular fluid.

      Privacy, Record keeping & confidentiality: All patients' data, information and study results
      will be kept under strict confidentiality and will be stored and kept as required. Only the
      primary researcher and the main investigator will have access to such data during the period
      of the study. At the end of the study all participants will be informed with the results and
      outcomes of the study as well as any health issues if found concerning them.

      The study has been approved and accepted by the Diagnosis, Oral Medicine and Periodontology
      Department as approved by the endorsement released from the departments' committee with the
      code: OMD-2021-11 on Sunday 7/11/2020.
    

Intervention name(s): Melaleuca Alternifolia Oil; Non-surgical periodontal debridement
Intervention type(s): Drug; Procedure
Intervention description(s): Tea tree oil 5% gel (Sigma Aldrich® Steinheim, Germany) for local sub gingival application was prepared by the Department of Pharmaceutics, Faculty of Pharmacy.
The gelling agent; Carbopol 940 (1% w/v) was first soaked in distilled water for 2 h then TTO dissolved in an appropriate amount of propylene glycol was added to the Carbopol dispersion. Methyl paraben 0.2% w/v dissolved in preheated water was used as a preservative. The gel mixture was then magnetically stirred for 30 min. Finally, pH was adjusted using 1 N NaOH added dropwise with gentle stirring with a spatula until the desired pH value (6.5-7) was reached. The gel was sterilized by autoclaving at 110 °C for 20 min.; Scaling and root surface debridement
Intervention MeSH terms: Tea Tree Oil
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: This study was designed to be a Randomized, Controlled, Parallel design, Two arms clinical trial. The patients will be randomly allocated to one of the two groups; test and control group using computer generated random tables (www.randomizer.org ) .
Masking: Single (Participant)
Primary purpose: Treatment
Keywords: Local Drug Delivery; Periodontitis; Tea Tree Oil