Effect of Nonsurgical Periodontal Therapy (NSPT) on Inflammatory Mediators, Subgingival Microbiota and Quality of Life Impacts in Rheumatoid Arthritis Subjects With Periodontitis
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 20
- 试验地点
- 2
- 主要终点
- Change in anti-carbamylated protein antibodies.
研究概览
简要总结
Periodontitis (PD), a chronic inflammatory disease which results in irreversible attachment loss, bone destruction and, if left untreated, tooth loss. Rheumatoid arthritis (RA), is an autoimmune disease characterized as a chronic inflammatory disorder leading to synovial inflammation and destruction of cartilage and bone. RA and PD which are commonly seen in elderly have many similarities in terms of pathophysiology and clinical progression. Previous findings from the investigators reported that inflamed periodontal tissues of RA subjects with PD are a potential site for post translational modification of proteins as there was increase in presence of citrullinated and carbamylated proteins in gingival tissues. Autoantibodies to these proteins have been reported to be involved in loss of immune tolerance which leads to RA and its progression. Currently there are gaps in our knowledge concerning the effect of nonsurgical periodontal therapy (NSTP), comprising oral hygiene instructions, scaling and root surface debridement on presence of these autoantibodies and inflammatory outcomes of RA. It is hypothesized that reduction in periodontal inflammation may concurrently reduce the systemic inflammatory load which is responsible in perpetuating RA joint inflammation. Here, the investigators propose to perform a randomized, controlled, single-blinded study on RA subjects with stage 2 or 3 periodontitis to assess the effect of NSTP on the reduction of these autoantibodies and inflammatory mediators as well as RA related disease activity measures such as ESR, CRP and Disease Activity Score 28-joint count (DAS28). The investigators will also assess changes in subgingival microbiota associated with RA-PD in response to NSTP using next generation sequencing. This study will help determine if RA individuals could benefit from early and appropriate NSPT, thus reducing periodontal inflammation and a similar impact on RA disease could be expected. This will ultimately improve patients' quality of life and reduce societal burden related to increased patient discomfort and treatment costs.
详细描述
Periodontitis (PD) is a chronic inflammatory disease which results in irreversible attachment loss, bone destruction and tooth loss. The primary aetiology of PD is the dental biofilm while the host inflammatory response causes the resulting tissue damage. PD is a major oral health problem worldwide and affects about 50% of the Malaysian population with 18% having severe PD. PD has been identified by the World Health Organisation to be a significant contributor to the global burden of oral disease and is reported to be the 6th most prevalent disease globally.
Rheumatoid arthritis (RA) is an autoimmune disease characterized as a chronic inflammatory disorder leading to synovial inflammation and destruction of the cartilage and bone. The aetiology of RA is unclear, however, prior to the clinical manifestations of RA, a preclinical immunological phase shown by the identification of serum autoantibodies is seen years before the development of RA. RA has a global prevalence of 1%, is more common in females and increases with age and has a deleterious effect on joint function and quality of life.
Many studies have concluded that there is a considerable positive association between PD and RA. Our previous study has shown that the prevalence of PD in RA subjects in University of Malaya Medical Centre was 33% with 18% of the RA subjects having severe forms of PD. Both PD and RA are chronic inflammatory diseases with similar host mediated pathogenesis and commonly seen in the elderly. They share numerous characteristics and pathogenic similarities with regards to lifestyle risk factors, immuno-genetics, disease progression and tissue destruction pathways to justify the hypothesis that there is a plausible link between them.
Prior to the onset of the clinical manifestations of RA, a pre-clinical immunological phase takes place whereby autoantibodies appear in patients' sera. Currently, the most studied autoantibodies are rheumatoid factor and anti-citrullinated protein antibodies (ACPA). Citrullination, which is a common post-translational modification of arginine to citrulline, is initiated by peptidiyl arginine deiminase enzymes (PADs) that are elevated at sites of inflammation.
It has been proposed that P. gingivalis, a bacteria commonly associated with periodontitis, is capable of citrullinating proteins through the P. gingivalis peptidyl arginine deiminase (PPAD) it releases as well as being autocitrullinated. Contradictory findings have also been reported in the literature about the presence of peptidyl citrulline-specific antibodies to PPAD (anti-PPAD antibodies) in RA and PD patients.
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 (Investigator, Outcomes Assessor)
盲法说明
single-blinded parallel arm study
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •All RA patients who fulfill the American College of Rheumatology (formerly the American Rheumatism Association) 2010 revised criteria for the classification of RA and who are unresponsive to conventional RA treatment.
- •At least 3 sites with probing pocket depths (PPD) ≥4mm and 4 sites with clinical attachment level (CAL) ≥4mm distributed in at least 2 quadrants (Papapanou et al, 2018) and will be designated as having Stage II and Stage III periodontitis
- •Patients should have a minimum of 12 teeth present.
排除标准
- •Patients who are on antibiotic use during the previous 3 months before study
- •Patients who have received nonsurgical periodontal treatment within 4 months before the study.
- •Patients who have any concurrent systemic or debilitating conditions such as uncontrolled diabetes.
- •Non Malaysian subjects
- •Patients who are pregnant
- •Presence of acute dental pain or infections
结局指标
主要结局
Change in anti-carbamylated protein antibodies.
时间窗: 6 months
The anticarbamylayed protein antibody is positive when the ELISA results exceeds a cut-off value of 6ng/mL.
Differential regulation in oral bacterial proteins
时间窗: 6 months
The protein regulation will be measured using proteomic technology with PEAKS X+ software. If the proteins are detected in both test group and control group, significant results are considered if there is \>2 fold change, occur in \>50% of the subjects, and the p-value is \<0.05. If proteins are only detected in either group, criteria to be used to consider a significant change is that the proteins are detected in \>50% of the subjects in the respective group.
次要结局
- Change in probing pocket depth (PPD)(6 months)
- Change in Anti-citrullinated protein levels(6 months)
- Change in Disease Activity Score 28-Erythrocyte sedimentation rate (DAS28-ESR) score.(6 months)
- Change in myeloperoxidase(6 months)