Clinical trial NCT05657015: Lepidium Sativum Extract Versus Simvastatin as an Adjunctive Local Delivery Agents to Non-Surgical Periodontal Therapy
Official title: Lepidium Sativum Extract Versus Simvastatin as an Adjunctive Local Delivery Agents to Non-Surgical Periodontal Therapy: A Randomized Controlled Clinical Trial With Biochemical Analysis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Periodontitis
Keywords: In situ gel
High Performance Thic Layer Chromatography
Local Drug Delivery
Lead sponsor: Ain Shams University
Sponsor class: OTHER
First posted: 2022-12-20
Enrollment: 30
Sex: ALL
Minimum age (years): 25
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
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).
Primary purpose: TREATMENT

Brief 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.

Eligibility criteria: Inclusion Criteria:

* Patients with ages ranging from 25 to 50 years old.
* Localized periodontitis, probing depth ≥5 mm. Less than 30% of teeth are involved.
* Both genders.
* Patients must be able to return for the recall visits and agreed to sign the written consent after a full explanation of the study.
* Systemically free according to the American Society of Anesthesiologists (ASA I).

Exclusion Criteria:

* Smokers
* Pregnant and lactating women or oral contraceptive usage
* Prisoners or abused individuals
* Unwilling patients to perform oral hygiene measures of plaque control.
* Patients with a history of allergy against any components of the two materials.
* Previous Periodontal treatment or any use of antibiotic/anti-inflammatory drugs within the last 6 months before the initiation of the study.

Primary outcomes:
measure: Assess clinically the plaque index (PI) in periodontitis patients
timeFrame: Change at baseline (after 1 week from the last debridement) and after 3 months follow-up period
measure: Asses clinically the mean sulcus bleeding index (MSBI) in periodontitis patients
timeFrame: Change at baseline (after 1 week from the last debridement) and after 3 months follow-up period
measure: Assess clinically the probing depth (PD) in periodontitis patients
timeFrame: Change at baseline (after 1 week from the last debridement) and after 3 months follow-up period
measure: Assess clinically the clinical attachment level (CAL) in periodontitis patients
timeFrame: Change at baseline (after 1 week from the last debridement) and after 3 months follow-up period
Secondary outcomes:
measure: Detect biochemically the nuclear factor kappa B (NF-κB) level in the gingival crevicular fluid (GCF).
timeFrame: Change from baseline to 1 month, from 1 month to 3 months, and from baseline to 3 months
Other outcomes:
Locations:
city: Cairo
country: Egypt
facility: Faculty of Dentitry, Ain Shams University
Study officials:
affiliation: Professor of Oral medicine, Periodontology, and Oral Diagnosis, Faculty of Dentistry, Ain Shams University, Egypt
name: Hala Abuelela, Professor
role: STUDY_DIRECTOR
affiliation: Professor of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Cairo university, Egypt
name: Olfat Shaker, Professor
role: STUDY_DIRECTOR
affiliation: Professor of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy (Girls), Al Azhar university, Egypt
name: Dina Osman, Professor
role: STUDY_DIRECTOR
affiliation: Lecturer of Oral Medicine, Periodontology, and Oral Diagnosis, Faculty of Dentistry, Ain Shams University, Egypt
name: Suzan Sarhan, PHD
role: STUDY_DIRECTOR
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