Lepidium Sativum Extract Versus Simvastatin as an Adjunctive Local Delivery Agents to Non-Surgical Periodontal Therapy
Condition: Periodontitis
MeSH terms: Periodontitis
Study type: Interventional
Phase: Phase 4

Summary: 
      The objectives of this clinical study were to:

        1. Assess the influence of Lepidium sativum in situ gel versus simvastatin gel on the
           clinical parameters in periodontitis patients as the primary objective.

        2. Detect the effect of locally delivered Lepidium sativum and simvastatin gels on the
           nuclear factor kappa B (NF-κB) level in gingival crevicular fluid as the secondary
           objective.
    

Detailed description: 
      Periodontitis is a multifactorial inflammatory disease that is triggered by the accumulation
      of oral biofilm on the tooth surface, leading to progressive destruction of the periodontal
      supporting tissues including loss of clinical attachment level, alveolar bone resorption, and
      formation of periodontal pockets due to apical migration of junctional epithelium. It is
      characterized by microbially-associated, host-mediated inflammation that leads to loss of
      periodontal apparatus. The formation of a bacterial biofilm begins with gingival
      inflammation; however, the initiation and progression of periodontitis are based on
      microbiome dysbiotic ecological changes in response to nutrients from gingival inflammatory
      and tissue breakdown products. So periodontitis is defined as a chronic immuno-inflammatory
      disorder affecting all the tooth-supporting structures. The conventional treatment of
      periodontitis involves scaling and root surface debridement (RSD) which is the supra and
      subgingival mechanical debridement of the periodontal pockets. RSD is done either by manual
      instruments or by ultrasonic devices. Although it may be effective alone, it has limitations
      such as in the case of deep periodontal pockets, inaccessible areas, and severe status of the
      disease. Therefore, this treatment should be supported by adjunctive antibacterial agents to
      remove the residual bacteria. Antibacterial agents have been used along with mechanical
      debridement in the management of periodontal infection. For about the past 30 years, locally
      delivered, anti-infective pharmacological agents have been introduced to achieve this goal.
      Since the disease is confined to the periodontium, local delivery of the drug in the pocket
      itself is the best option. The pocket acts as a natural reservoir and provides easy access
      for the insertion of a medicinal device. Drug release and distribution throughout the pocket
      are provided by gingival crevicular fluid (GCF), which acts as the leaching medium. Also,
      significant drug levels can be maintained in the GCF for a prolonged duration. Local delivery
      drugs can overcome most of the adverse side effects of systemic agents. All these factors
      make intra-pocket drug delivery an ideal choice. Statins such as simvastatin (SMV) have been
      considered as an adjunct to non-surgical periodontal therapy. Statins were initially imported
      as cholesterol-reducing drugs, which is performed by hindering the 3-hydroxy-3-methylglutaryl
      coenzyme A (HMG-CoA) reductase. Statins also have additional properties including;
      anti-inflammatory, anti-oxidant, anti-bacterial, and other pleiotropic effects such as
      blocking the release of pro-inflammatory mediators and matrix metalloproteinases (MMPs).
      Therefore, statins have been shown to promote bone formation and have proven to be effective
      in periodontal therapy. Nowadays, there are many researchers using plants as adjunctive
      therapy to the non-surgical periodontal treatment of disease because of their efficacy,
      safety, and therapeutic prominence. Lepidium sativum (LS) is one of the herbal products that
      is used daily without any regard for its benefits. It is an annual, edible herb that belongs
      to the family of Brassicaceae. It originated in Ethiopia and is found in many countries such
      as Saudi Arabia, India, and Egypt, and later in Europe. It had other names such as garden
      cress, halon, Hab Al-Rashad, and Thuffa. It is composed of seeds, leaves, and roots. All of
      its parts were important for medicinal effects. It has a peppery flavor so it can be used for
      homemade foods (as salads, and sandwiches), especially the leaves. The seeds can be used in
      many therapeutic domains as an anti-hyperglycemia, anti-hyperlipidemia, anti-diarrhea,
      anti-rheumatic, hepatoprotective, antioxidant, anti-inflammatory, and anti-microbial and in
      gastrointestinal, skin, and respiratory diseases, and some bone fractures healing. LS seeds
      contain many several phenols, minerals, proteins, fatty acids, vitamins, and carbohydrates.
      Because of its polyphenols composition, it has anti-microbial activity against several
      bacteria such as (P. auregenosa, S. aureus, and E. coli). The plant's antioxidative effect
      decreases the generation of reactive oxygen species on human cells and thus decreases the
      destruction of the disease. Oxygen stress plays an important role in the occurrence of many
      human diseases due to an increase in reactive oxygen species (ROS) production. Because of the
      anti-oxidant activity of the LS and cytoprotective effects, the pre-treatment with this plant
      can lead to inhibition of ROS generation. Tumor necrosis factor α (TNF-α), interleukin 6 and
      10 (IL-6, IL-10), and nitric oxide (NO) are the pro-inflammatory mediators that play an
      important role in disease damage. Nuclear factor kappa B (NF-kB) also plays a role in
      inflammation by inducing the transcription of TNF-α on bacterial lipopolysaccharides (LPS).
      LPS may alter the anti-oxidative activity and enhance the production of inflammatory
      mediators. Therefore, the administration of LS seed extract will decrease the effectiveness
      of the bacteria and improve general health.

      Due to the lack of studies that used LS as a therapeutic agent in periodontitis, the current
      study was performed to evaluate this plant's efficacy in the management of periodontitis.
      Furthermore, due to the pleiotropic effects of Simvastatin and Lepidium sativum, the present
      study was carried on to assess the influence of LS gel versus simvastatin gel as an adjunct
      to non-surgical periodontal therapy. Moreover, the effects of SMV and LS on the level of
      NF-κB in GCF were assessed.
    

Intervention name(s): Lepidium Sativum; Simvastatin
Intervention type(s): Drug; Drug
Intervention description(s): 2 ml of LS in situ gel at baseline; 1.2% of SMV in situ gel at baseline
Other intervention name(s): Garden cress
Intervention MeSH terms: Simvastatin
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: This study was designed to be a Randomized, Controlled, Triple-blinded, Phase (IV) clinical trial; the eligible participants were randomly allocated to one of the two comparative parallel groups; test and control group using computer-generated random tables (www.randomizer.org).
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: In situ gel; High Performance Thic Layer Chromatography; Local Drug Delivery