Glucosamine Sulphate Versus Ginger in Non-Surgical Periodontal Therapy
Condition: Periodontal Pocket
MeSH terms: Periodontal Pocket
Study type: Interventional
Phase: Phase 2

Summary: 
      Glucosamine (GlcN) is an N-deacetyl amino monosaccharide sugar derived from complete
      hydrolysis of chitosan in which it is important vector for chondroitin and keratin sulfate,
      while on the other hand, medicinal plants became a source of great economic benefit
      worldwide, ginger has been found to have biological activities such as antioxidant,
      anti-inflammatory, antimicrobial, and anticancer activities. So, these effects which made it
      a good candidate to be used in periodontal therapy. The main objective of this study is to
      assess and compare the effect of locally delivered glucosamine sulphate gel versus ginger gel
      on the clinical parameters in periodontitis patients including Plaque index (PI), Means
      sulcus bleeding index (MSBI), Probing depth (PD), Clinical attachment loss (CAL). and to
      detect the effect of locally delivered both gels on RANKL level in gingival crevicular fluid.
    

Detailed description: 
      Periodontitis was described as a chronic multifactorial inflammatory disease associated with
      formation of plaque biofilms and characterized by progressive destruction of the
      tooth-supporting apparatus. Its primary manifestation includes the loss of periodontal tissue
      support, featured through clinical attachment loss (CAL) and radiographically alveolar bone
      loss with the presence of periodontal pockets which are a significant mark of the disease,
      hence, can progressively lead to tooth loss and gingival bleeding.

      The new classification of periodontal and peri-implant diseases and conditions in 2017
      classified these diseases into four main categories: First category concerned with
      periodontal health & gingival diseases either dental biofilm induced gingivitis or non-dental
      biofilm induced gingivitis. Second category concerned with periodontitis which can be
      classified into necrotizing periodontitis, periodontitis as a manifestation of systemic
      disease and periodontitis which include the forms of the disease previously recognized as
      "chronic" or "aggressive". Third category concerned with other conditions can affect the
      periodontium as systemic diseases, traumatic occlusion, mucogingival deformities, tooth
      related factors, periodontal abscesses and endodontic-periodontal diseases. Fourth category
      concerned with peri-implant diseases and conditions as peri-implant health, peri-implant
      mucositis, peri-implantitis and peri-implant soft & hard tissue deficiencies.

      But now, Periodontitis can be described into four stages depending on the clinical attachment
      loss (CAL) starting from Stage 1: Initial periodontitis (CAL 1-2 mm), Stage 2: Moderate
      periodontitis (CAL 3-4 mm), Stage 3: Severe periodontitis with potential for additional tooth
      loss and Stage 4: Severe periodontitis with potential for loss of dentition (CAL ≥5 mm).
      Grading focuses on assessment of the risk factors as smoking, systemic factors as diabetes,
      and outcomes of non-surgical periodontal therapy. Grade A: Slow rate of progression (no CAL
      loss over 5 years), Grade B: Moderate rate of progression (CAL loss <2 mm over 5 years) and
      Grade C: Rapid rate of progression (≥2 mm over 5 years).

      The pathogenesis of periodontal diseases is mediated by the inflammatory response to bacteria
      in the dental biofilm. The immune response to infection is regulated by cytokine and
      chemokine signals. Cytokines and chemokines (chemotactic cytokines) are the messages between
      cells. Cytokines are low-molecular-weight proteins involved in the initiation and advanced
      stages of inflammation, in which they can regulate the amplitude and the duration of the
      response. The genetic regulation leading to the secretion of proinflammatory cytokines from
      various cells is generally depending on the activation of nuclear factor kappa-B
      transcription. Cytokines are produced by resident cells, such as epithelial cells and
      fibroblasts, and by phagocytes (neutrophils and macrophages) in the acute and early chronic
      phases of inflammation, and by immune cells (lymphocytes) in early and advanced lesions.
      After recognition of the presented microbes to the appropriate cells, cytokines of the innate
      response, including tumor necrosis factor alpha, interleukin-1beta and interleukin-6, are the
      first to face in the pathogenesis pathways of the periodontal disease. It is suggested that
      individuals who produce high levels of these mediators in response to such thing will go
      through more and severe tissue loss.

      In General, periodontitis is a chronic inflammation in which elimination of the virulent
      factors can be necessary in treatment of periodontitis by initial intervention by scaling and
      root surface debridement So, we should know about the importance of human gingival
      fibroblasts (HGFs). First, HGFs represent most prominent cells in periodontal tissue.
      Lipopolysaccharides (LPS)-treated HGFs produce inflammatory cytokines such as IL-6 and IL-8
      and inflammatory chemical mediators such as Prostaglandin (PGE2), and second; HGFs continue
      to produce PGE2 IL-6, and IL-8 in the presence of LPS, unlike macrophages. So, it is known
      that large number of chemical mediators and cytokines was obtained from HGFs can be within
      the periodontal tissues. That kind of oral infection can be restricted by using antimicrobial
      mouth wash such as chlorhexidine. usual handling of these chemicals may induce unwanted
      adverse effects such as tooth staining, taste alteration and development of hypersensitivity
      reactions.

      Antibiotics such as penicillin have been notified for dental caries prevention in humans and
      animals, merely they reported many side effects, added to the development of the bacterial
      resistance, so here comes the reason for a deep need for natural antibacterial substitutes.
      One of the strongest substitutes are medicinal plants.

      Glucosamine is a biological element of joint cartilage, it has been known as popular systemic
      supplement combined with chondroitin sulfate for knee osteoarthritis (OA), as so these
      compounds could have a chondro-protective effect on knee OA. It is an amino monosaccharide in
      which it is important vector for chondroitin and keratin sulfate and also, an independent
      meta-analysis has shown that in trials using a particular formulation of glucosamine as the
      crystalline glucosamine sulfate (pCGS) gives better result on pain than other preparations of
      glucosamine did. Glucosamine has a role as a part of glucosaminoglycans (GAGs), it reveals an
      anti-inflammatory action in vitro and in vivo GlcN reduce the releasing of inflammatory
      mediators such as nitric oxide (NO), prostaglandin (PG) E2 and interleukin (IL)-8 by
      chondrocytes and synovial cells. These outcomes propose that GlcN expresses an
      anti-inflammatory effect on chondrocytes and synovial cells, hence revealing a protective
      action on OA. Chondroitin-sulphate (CS) and glycosamine-sulphate (GS) has proved a direct
      effect on OA in combination or alone, as CS has a direct effect on suppressing the production
      of osteoprotegerin OPG and RANKL the main two major factors involved in the remodeling
      process, and GS especially has a significant effect. In vitro studies have shown that
      glucosamine prevents bone resorption by means of down-regulation of RANKL expression in the
      joints, through lowering the number of RANKL positive T cells and the level of sRANKL in the
      joint's extracts.

      On the other hand, medicinal plants became a source of great economic benefit worldwide. The
      recent natural recipes utilizing medicinal plants is giving a natural replacement for
      antibiotic unpleasant effects such as supra infections, hypersensitivity reaction and teeth
      staining. In addition, using of systemic antibiotics against oral infections is not
      recommended because of the risk for development of bacterial resistance. However, the
      discovery of natural extracts of medicinal plants with antimicrobial and anti-inflammatory
      activity will be valuable and safe.

      Ginger (Zingiber officinale Roscoe), which belongs to the Zingiberaceae family and the
      Zingiber genus, has been commonly consumed as a spice and an herbal medicine for a long time.
      Bioactive compounds such as terpene and phenolic compounds have been recognized in ginger.
      The phenolic compounds are mainly gingerols, shogaol, and paradols, they resemble for
      different bioactivities of ginger. Ginger has been found to have biological activities such
      as antioxidant, anti-inflammatory, antimicrobial, and anticancer activities. A lot of studies
      have revealed that ginger can affect many diseases, such as cardiovascular diseases,
      neurodegenerative diseases, obesity, diabetes mellitus, chemotherapy-induced nausea and
      emesis, and respiratory disorders. So, more attention will be focused on the bioactivities of
      the ginger.

      In fresh ginger the major polyphenols are gingerols such as 6-gingerol, 8-gingerol, and
      10-gingerol. Which if heat treated or stored for long time turns into into corresponding
      shogaol and after hydrogenation, shogaol can be transformed into paradols. It was found that
      overproduction of free radicals, such as reactive oxygen species (ROS), plays a strong role
      in the initiation of many chronic diseases.

      Antioxidant activity: studies have shown that ginger has a protective effect against reactive
      oxygen species (ROS) as it showed antioxidant effects in the chondrocyte cells of human, with
      oxidative stress mediated by interleukin-1β (IL-1β). It lowers the production of ROS and
      lipid peroxidation and stimulates the expression of several antioxidant enzymes (). Ginger
      and its bioactive compounds (such as 6-shogaol) exerting an antioxidant role via the nuclear
      factor erythroid 2-related factor 2 (Nrf2) signaling pathway.

      Anti-Inflammatory Activity: several studies has conveyed that ginger, and its active
      compounds has anti-inflammatory activity which can protect against inflammation-related
      diseases The anti-inflammatory effects were mostly related to phosphatidylinositiol -3-kinase
      (PI3K), protein kinase B (Akt), and the nuclear factor kappa light chain-enhancer of
      activated B cells (NF-κB). Adding that 6-shogaol exhibited a protective impact against tumor
      necrosis factor α (TNF-α). It also down regulates the Claudin-2 and the disassembly of
      Claudin-1 via the suppression of signaling pathways involved with PI3K/Akt and NF-κB.
      Moreover, nanoparticles derived from edible ginger (GDNPs 2) could increase the levels of
      anti-inflammatory cytokines such as interleukin-10 (IL-10) and IL-22 and decreasing the
      levels of pro-inflammatory cytokines such as TNF-α, IL-6, and IL-1β specifically
      nanoparticles loaded with 6-shogaol so help in lowering the inflammatory process.

      Cytotoxicity: Ginger has been examined and considered for its anticancer properties against
      different types of cancers, such as breast, cervical, prostate, and colorectal cancer Where
      its mechanisms of action are represented in the inhibition of proliferation and the induction
      of apoptosis in cancer cells.

      Antidiabetic Activity: Diabetes mellitus is known as a serious metabolic disorder condition
      caused by insulin deficiency and/or insulin resistance, which results in an abnormal rising
      in blood glucose. Prolonged hyperglycemia could speed up the protein glycation production
      which results in formation of advanced glycation end products (AGEs). An in vitro study
      resulted in both 6-shogaol and 6-gingerol preventing the progression of diabetic
      complications, and how they prevent the production of AGEs by trapping methyl-glyoxal (MGO),
      the precursor of AGEs Other several studies have investigated the antidiabetic effect of
      ginger and its major active elements.
    

Intervention name(s): Glucosamine Sulfate; Ginger Oil
Intervention type(s): Drug; Drug
Intervention description(s): Glucosamine sulphate (GLcN) is an N-deacetyl amino sugar derived from the complete hydrolysis of the chitosan with significant anti-inflammatory action.; Ginger (Zingiber officinale Roscoe) has been found to have biological activities such as antioxidant, anti-inflammatory, antimicrobial, and anticancer activities.
Other intervention name(s): Glucosamine sulphate; Ginger; Zingiber officinale; Zingiber genus
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: supra and sub gingival scaling will be performed to all patients followed by application of local delivery drug within two groups to assess the effects after 1 month then 3 months.
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: glucosamine sulphate; ginger; local delivery