The Effect of Professional Mechanical Plaque Removal (PMPR) and Chlorhexidine Mouthwash on Salivary and Acquired Enamel Pellicle (AEP) Proteins and Vascular Function and Inflammation in People With Periodontal Disease
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 发起方
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Proteomics - Salivary Protein Analysis
研究概览
简要总结
- Gum inflammation is called gingivitis. Gum disease, known as periodontal disease, is a long-term inflammation of the gums and bone around teeth, leading to tooth loss. Both gingivitis and periodontal disease are also linked to other health problems, including heart disease. Additionally, salivary proteins play a role in maintaining oral health. For example, a protective layer called the salivary pellicle (SP) forms on teeth after tooth brushing and helps defend against harmful bacteria.
- Nitrate-reducing bacteria (NRB) are also present in saliva and play a role in oral and cardiovascular health by converting nitrate to nitric oxide (NO). This compound supports blood vessel health and overall cardiovascular function. Therefore, NRB's abundance is linked to lower blood pressure and improved cardiovascular health.
- Standard treatments for gum disease include deep cleaning (also called professional mechanical plaque removal, or PMPR), and sometimes chlorhexidine (CHX) mouthwash is used with PMPR to help reduce mouth bacteria. However, while CHX is effective against plaque (a sticky film of bacteria on the tooth surface), it may reduce the activity of "nitrate-reducing" bacteria (NRB), which are important for producing nitric oxide (NO).
- This study investigates the impact of deep cleaning (PMPR) with and without Chlorhexidine mouthwash on salivary and SP proteins, as well as blood vessel function, in people who have gum disease. By examining these links, the investigators aim to gain a deeper understanding of how oral care practices may impact overall health, particularly heart health.
详细描述
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**Introduction**
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Periodontal disease (PD) is a chronic inflammatory condition affecting the tissues supporting teeth, including gums, bone, and ligaments, and is associated with a 19% increased risk of cardiovascular disease. It starts with gum inflammation, known as gingivitis. Both chronic gingivitis and PD have multiple causes including poor oral hygiene, smoking, diabetes, genetics, stress, age, and certain medications, and PD contributes significantly to healthcare costs ($54 billion direct, $25 billion indirect annually).
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The key approach for managing PD is non-surgical, typically involving Professional Mechanical Plaque Removal (PMPR), with or without adjunct antiseptic mouthwashes such as 0.2% chlorhexidine (CHX). While CHX is effective in reducing dental plaque, concerns exist regarding its impact on beneficial oral nitrate-reducing bacteria (NRB), which play a critical role in systemic nitric oxide (NO) pathways and cardiovascular homeostasis. Altering the oral microbiome may influence vascular function, including blood pressure and endothelial health.
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This study investigates the effects of PMPR, performed as standard periodontal therapy, and adjunctive CHX mouthwash on salivary and acquired enamel pellicle (AEP) proteins, oral microbiome, NRB activity, and vascular function in individuals with PD.
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**Study Design Overview**
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A total of 30 adult participants with clinically confirmed gingivitis and/or periodontal disease will be enrolled and followed at four assessment points over a three-month period.
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Recruitment Process and Practicalities
Under the supervision of the academic supervisor, potential research participants will be recruited via the following steps:
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Research participants recruited from SDHCP dental clinics:
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Step 1: Providing Study Information to Potential Participants Clinicians at the University of Portsmouth (SDHCP), Dr. Anish Patel, Prof. Chris Louca, and Dr. Bhavin Dedhia, will inform patients about the study during their routine clinical appointments. Study materials, including the Participant Information Sheet and Invitation Letter, will be provided at least 24 hours before the first appointment, allowing individuals time to consider participation.
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Step 2: Participant Follow-Up Participants who wish to volunteer for the study will then be contacted by the research team. The PhD researcher will explain the study in more detail, answer any questions, and confirm their willingness to participate. This process ensures that participants have at least 24 hours to consider their involvement before their appointment. The consent form will be signed by the individuals in person, before their oral screening, on their first visit.
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Eligibility Screening: Consented participants will undergo a routine clinical examination by the clinicians using the standard British Society of Periodontology (BSP) 2017 classification, focusing on individuals with BPE codes 1 to 4 for gingivitis and subsequent diagnosis of periodontitis (stages 1 and 2).
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Research participants recruited from community centres:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 30 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants must have a minimum of 2 natural teeth in each sextant (at least 12 teeth overall).
- •Individuals with clinically diagnosed gingivitis and/or early periodontitis (stage 1 and 2)
- •Must not have undergone periodontal maintenance therapy (PMPR) within the last 6 months.
- •Must not currently be wearing orthodontic appliances, due to their effect on oral microbiota and plaque composition.
- •Must not be using removable orthodontic appliances, as they increase plaque accumulation.
- •Must not have taken any antibiotic treatments within the last 3 months.
- •Must be able to provide written informed consent.
- •Individuals with dental erosion or caries will still be included but matched during the baseline visit.
排除标准
- •Individuals under regular medication within one month of the study start date for any medical condition (such as hypertension and/or diabetes)
- •Pregnant or breastfeeding individuals.
- •Individuals requiring an interpreter or who are non-English speakers.
- •Individuals unable to provide written informed consent.
- •Individuals participating in another ongoing clinical study (other than observational studies) within 3 months prior to or during this study.
- •Individuals who have used mouthwash or tongue scrapers in the last 6 weeks.
- •Individuals who consume 20 or more cigarettes per day.
- •Individuals who consume more than 5 alcoholic drinks per day.
结局指标
主要结局
Proteomics - Salivary Protein Analysis
时间窗: Analysed for WMS samples collected on Day 0, Day 1, Day 14, and Day 90.
Purpose: To identify inflammatory and protective proteins, monitor changes post-PMPR in saliva. * Method ( Protocol from Imperial College, London): * Reduction \& Alkylation: A 10 μL aliquot of saliva will be thawed and mixed with 7 μL of ammonium bicarbonate buffer on ice. For reduction and alkylation, 5 μL each of TCEP and CAA will be added, maintaining a pH of 7-8 to ensure proper modification of disulfide bonds and cysteine residues. * SP4 Protocol: Following reduction and alkylation, the SP4 protocol will be implemented by adding 80 μL of LC/MS-grade acetonitrile to precipitate proteins; the mixture will be centrifuged to separate the supernatant, and the pellet will be washed three times with ethanol for thorough purification. * Digestion: The purified pellet will then be resuspended in stock trypsin by adding 20 μL 25 mM ammonium bicarbonate to lyophilised powdered trypsin (powdered sequencing grade modified trypsin) and incubate overnight at 37°C, and incubated overnight.
次要结局
- Salivary Flow-Rate(Day 0, Day 1, Day 14, and Day 90)
- Salivary pH(Day 0, Day 1, Day 14, and Day 90)
- Oral Microbial Composition(Day 0, Day 1, Day 14, and Day 90)
- Acquired Enamel Pellicle (AEP) Protein Composition(Day 0, Day 1, Day 14, Day 90)
- Nitrate Reducing Activity of the Oral Bacteria(Analysed for the nitrate rinse samples collected on Day 0, Day 1, Day 14, and Day 90.)
- Flow-Mediated Dilation (FMD)- Large Blood Vessel Endothelial Function Test (Ultrasound)(On Day 0, upon participant arrival at the first visit, prior to PMPR treatment. On Day 1, i.e. 24 hours after PMPR treatment. On Day 14, two weeks following chlorhexidine/placebo mouthwash use, and then on Day 90, three months post-PMPR treatment.)
- Iontophoresis- Small Blood Vessel Endothelial Function Test(On Day 0, upon participant arrival at the first visit, prior to PMPR treatment. On Day 1, i.e. 24 hours after PMPR treatment. On Day 14, two weeks following chlorhexidine/placebo mouthwash use, and then on Day 90, three months post-PMPR treatment.)
- Cardiac Output (CO)(On Day 0, upon participant arrival at the first visit, prior to PMPR treatment. On Day 1, i.e. 24 hours after PMPR treatment. On Day 14, two weeks following chlorhexidine/placebo mouthwash use, and then on Day 90, three months post-PMPR treatment.)
- Pulse Wave Analysis (PWA)(On Day 0, upon participant arrival at the first visit, prior to PMPR treatment. On Day 1, i.e. 24 hours after PMPR treatment. On Day 14, two weeks following chlorhexidine/placebo mouthwash use, and then on Day 90, three months post-PMPR treatment.)
- Pulse Wave Velocity (PWV)(On Day 0, upon participant arrival at the first visit, prior to PMPR treatment. On Day 1, i.e. 24 hours after PMPR treatment. On Day 14, two weeks following chlorhexidine/placebo mouthwash use, and then on Day 90, three months post-PMPR treatment.)
- Salivary Nitrite Concentration(Day 0, Day 1, Day 14, and Day 90.)
- Salivary Nitrate Concentration(Day 0, Day 1, Day 14, and Day 90.)
- Plasma Nitrite Concentration(Day 0, Day 1, Day 14, and Day 90)
- Plasma Nitrate Concentration(Day 0, Day 1, Day 14, and Day 90)
- Blood Pressure (BP)(On Day 0, upon participant arrival at the first visit, prior to PMPR treatment. On Day 1, i.e. 24 hours after PMPR treatment. On Day 14, two weeks following chlorhexidine/placebo mouthwash use, and then on Day 90, three months post-PMPR treatment.)
- Inflammatory Biomarkers in Blood(Analysed for the venous blood samples collected on Day 0, Day 1, Day 14, and Day 90.)
- Efficacy of PMPR ± CHX Mouthwash on Bleeding on Probing (Periodontal Clinical Index)(Day 0, Day 1, Day 14, Day 90)
- Efficacy of PMPR ± CHX Mouthwash on Probing Pocket Depth (Periodontal Clinical Index)(Day 0, Day 1, Day 14, Day 90)
- Efficacy of PMPR ± CHX Mouthwash on Clinical Attachment Level (Periodontal Clinical Index)(Day 0, Day 1, Day 14, Day 90)
- Efficacy of PMPR ± CHX Mouthwash on Plaque Index(Day 0, Day 1, Day 14, Day 90)
- Efficacy of PMPR ± CHX Mouthwash on Gingival Index(Day 0, Day 1, Day 14, Day 90)
研究者
Mahdi Mutahar
Dr. Mahdi Mutahar
University of Portsmouth