Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT06200415 |
| Other study ID # |
FDASU-Rec IM012013 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
Phase 2
|
| First received |
|
| Last updated |
|
| Start date |
November 8, 2022 |
| Est. completion date |
August 8, 2023 |
Study information
| Verified date |
January 2024 |
| Source |
Ain Shams University |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial 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.
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.
