Lepidium Sativum Extract Versus Simvastatin as an Adjunctive Local Delivery Agents to Non-Surgical Periodontal Therapy

Sponsor

Ain Shams University (Other)

Overall Status

Completed

CT.gov ID

NCT05657015

Collaborator

(none)

Enrollment

Location

Arms

Actual Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The objectives of this clinical study were to:

Assess the influence of Lepidium sativum in situ gel versus simvastatin gel on the clinical parameters in periodontitis patients as the primary objective.
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.

Condition or Disease	Intervention/Treatment	Phase
Periodontitis	Drug: Lepidium Sativum Drug: Simvastatin	Phase 4

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

30 participants

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).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)

Masking Description:

The phytochemicals were prepared by the pharmacist and coded so that the patients, researcher, and outcomes assessor were blinded to the type of intervention.

Primary Purpose:

Treatment

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

Actual Study Start Date :

Sep 1, 2021

Actual Primary Completion Date :

May 1, 2022

Actual Study Completion Date :

Jul 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Lepidium sativum 15 participants 15 participants with localized stage II or III, and grade A periodontitis received about 2ml of locally delivered Lepidium sativum in situ gel with scaling and root surface debridement once at the beginning of the study	Drug: Lepidium Sativum 2 ml of LS in situ gel at baseline Other Names: Garden cress
Active Comparator: simvastatin 15 participants with localized stage II or III, and grade A periodontitis received about 1.2% of locally delivered Simvastatin in situ gel with scaling and root surface debridement once at the beginning of the study	Drug: Simvastatin 1.2% of SMV in situ gel at baseline

Arm

Intervention/Treatment

Experimental: Lepidium sativum

15 participants 15 participants with localized stage II or III, and grade A periodontitis received about 2ml of locally delivered Lepidium sativum in situ gel with scaling and root surface debridement once at the beginning of the study

Drug: Lepidium Sativum

2 ml of LS in situ gel at baseline

Other Names:

Garden cress

Active Comparator: simvastatin

15 participants with localized stage II or III, and grade A periodontitis received about 1.2% of locally delivered Simvastatin in situ gel with scaling and root surface debridement once at the beginning of the study

Drug: Simvastatin

1.2% of SMV in situ gel at baseline

Outcome Measures

Primary Outcome Measures

Assess clinically the plaque index (PI) in periodontitis patients [Change at baseline (after 1 week from the last debridement) and after 3 months follow-up period]
Percentage of tooth surfaces with bacterial deposits. Plaque index scores were recorded at six sites per tooth (mesiobuccal, buccal, disto-buccal, mesio-lingual, lingual, disto-lingual).The plaque index visually records the score such as 0,1,2, and 3 using the standard probe.
Asses clinically the mean sulcus bleeding index (MSBI) in periodontitis patients [Change at baseline (after 1 week from the last debridement) and after 3 months follow-up period]
Percentage of tooth surfaces with bleeding point sites on probing. Bleeding index scores were recorded at six sites (mesiobuccal, buccal, disto-buccal, mesio-lingual, lingual, disto-lingual). The scores were recorded as 0,1,2,3,4, and 5.
Assess clinically the probing depth (PD) in periodontitis patients [Change at baseline (after 1 week from the last debridement) and after 3 months follow-up period]
The distance between the margin of the gingiva and the base of the pocket was recorded at four points (mesio-facial, mid-facial, disto-facial, and mid-lingual) to the nearest millimeter using the University of Michigan O' probe with Williams' graduations in conjunction with an occlusal stent for the standardization of readings. The probe was inserted parallel to the long axis of the tooth.
Assess clinically the clinical attachment level (CAL) in periodontitis patients [Change at baseline (after 1 week from the last debridement) and after 3 months follow-up period]
The CAL was measured in millimeters from the cemento-enamel junction (CEJ) to the base of the pocket using the University of Michigan O' probe with Williams' graduations in conjunction with an occlusal stent for the standardization of readings.

Secondary Outcome Measures

Detect biochemically the nuclear factor kappa B (NF-κB) level in the gingival crevicular fluid (GCF). [Change from baseline to 1 month, from 1 month to 3 months, and from baseline to 3 months]
Levels of NF-κB (ng/ml) in GCF samples were determined by using a commercially available means of Enzyme Linked Immuno Sorbent Assay (ELISA) according to the manufacturer's recommendations. The GCF samples were collected using perio-paper strips (Oraflow Inc., Smithtown, New York, USA). Perio-paper strips visually contaminated with blood were discarded. The samples were immediately placed into a sterile, labeled Eppendorf tube and stored at -20 ºC for subsequent assays. Each perio-paper was soaked with 200ul of phosphate buffering saline (PBS), vortexed, and centrifuged. A supernatant was used for the detection of NF-κB. The kit was provided by Bioassay Technology Laboratory (China) Cat No E7121 Hu.

Eligibility Criteria

Criteria

Ages Eligible for Study:

25 Years to 50 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Faculty of Dentitry, Ain Shams University	Cairo		Egypt

Sponsors and Collaborators

Ain Shams University

Investigators

Study Director: Hala Abuelela, Professor, Professor of Oral medicine, Periodontology, and Oral Diagnosis, Faculty of Dentistry, Ain Shams University, Egypt
Study Director: Olfat Shaker, Professor, Professor of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Cairo university, Egypt
Study Director: Dina Osman, Professor, Professor of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy (Girls), Al Azhar university, Egypt
Study Director: Suzan Sarhan, PHD, Lecturer of Oral Medicine, Periodontology, and Oral Diagnosis, Faculty of Dentistry, Ain Shams University, Egypt