Treatment of Periodontal Disease in Systemic Lupus Erythematosus

Study Overview
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Brief Summary
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The primary objective of this study is to: Part 1 - Baseline Comparisons The primary objective of Part 1 is to: Investigate the association between SLE and a measures of vascular health (brachial artery flow-mediated dilatyation) in patients with Systemic Lupus Erythematosus (SLE) and a healthy periodontium compared to patients with SLE and Periodontitis (PD) Part 2 - Pilot Randomized Clinical Trial To assess the effect of Periodontal Treatment (PT) on the endothelial function in a population of patients suffering from SLE and PD. Secondary Secondary objectives include: Part 1 - Baseline Comparisons The secondary objectives of Part 1 are to investigate the association of: Inflammatory biomarkers in saliva and blood and periodontal status in patients with SLE and PD and those with SLE and a healthy periodontium The oral microbiome using plaque analysis and periodontal status in patients with SLE and PD and those with SLE and a healthy periodontium Part ParPa Part 2 - Pilot Randomized Controlled Trial Evaluate the effect of PT on biomarkers of SLE disease severity/progression in a population of patients suffering from SLE and PD. Evaluate the effect of PT on the B cell panel in a population of patients suffering from SLE and PD. Evaluate effect of PT on the systemic inflammatory and oxidative profile of a population of patients suffering from SLE and PD. Evaluate effect of PT on skin lesions in a population of patients suffering from SLE and PD.

Detailed Description
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The primary endpoints of this study are in two parts. One part is to quantify the vascular health in response to PD as a static point prior to active therapy compared to participants with SLE and healthy perdiodontium . The second part is to quantify and compare the clinical and systemic outcomes of cases with SLE and PD following periodontalal treamtment. Part 1 Comparative analyses between cases (SLE with PD) and controls (SLE without PD) will be performed using ANOVA analysis. Primary outcome will be the difference in flow -mediated dilatation between groups. Multivariate analysis will be performed to adjust for a number of covariates including: age, gender, body mass index, ethnicity and supragingival plaque levels. All secondary endpoints will be analysed with ANOVA. Pre-specified analyses of secondary outcomes will include descriptive analyses and differences. Part 2 Primary clinical periodontal outcome will be the difference in mean flow mediated (peri-implant) at 6 months between study groups and analysed by analysis of co-variance model. Age, gender, body mass index, smoking status, ethnicity and dental plaque levels will be included as additional covariates. Pair-wise comparison and between groups differences will be calculated using Tukey HSD corrections. If the normality assumption does not seem reasonable even after transformation of original values, equivalent nonparametric methods will be used. Primary systemic inflammatory outcome will be Changes in FMD (primary outcome), circulating inflammatory, vascular and oxidative biomarkers (secondary outcomes) will be analysed with analysis of variance for repeated measures using a conservative F-test (Greenhouse-Geisser correction). If a treatment by time interaction will be found, pair-wise comparisons will be performed (Bonferroni-Holm adjustment). Side effects and safety data will be summarized using standard descriptive statistics. Significance will be set to be at p < 0.05. Experimental Design Participants will be approached by the members of healthcare research team explaining the possibilities to be included in the project. There will be limit in time (24 Hours) to decide whether participate, subject to the recruitment completion.. A sufficient number of participants meeting the necessary inclusion/exclusion criteria will be accepted for the study in order to recruit 30 patients suffering from SLE and PD. Participants who consent to this study will undergo a baseline visit (Sample size 200) in which they will have a comprehensive full mouth periodontal probing depths assessment. In addition, full mouth plaque and gingival bleeding scores will also be calculated. A series of parameters will be recorded (including age, gender, ethnicity, and body mass index). Saliva samples (1 ml) and Blood samples (32 ml) will also be collected for analysis of peripheral blood inflammatory and oxidative biomarkers. Blood cell counts, C-reactive protein, complement levels, dsDNA autoantibodies, kidney and liver function tests will also be performed. The vascular function will be assessed by means of an ultrasound scan. After randomization (selected 30 patients) to either Test or Control Group, the test group will undergo periodontal treatment in 2 sessions within a week from each other. Radiographic examination Orthopentomogram (OPG) will be taken at the second visit of patient's visit only. Optical coherence tomography will be done on the patients in vist (2,4 and 6). At 2 months both groups will be reassessed, and the same information and samples taken at baseline will be collected. The test group will undergo additional periodontal treatment visit (3) of Intensive periodontal treatment/IPT) within 3 weeks from the 2 months visit. After this visit the Control group will receive the same periodontal treatment (Control periodontal treatment/CPT). At 6 months both groups will be seen for the final study assessment. If at any of the study assessment (2 months and 6 months) participants in the control group show signs of progression of PD they will be treated separately and exited from the trial. After 6 months all the participants will have treatment irrespective of groups, if they require treatment it will provided

Official Title
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Treatment of Periodontal Disease in Systemic Lupus Erytematosus: A Pilot Randomized Controlled Clinical Trial

Conditions
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Systemic Lupus Erythematosus, Periodontitis

Intervention / Treatment
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* Procedure: supra/sub gingival root surface debridement
* Procedure: supra-gingival scaling and polishing


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male/Female Subject must be 18 years of age or over. Patients with 4 or more criteria for juvenile systemic lupus erythematosus (JSLE) or SLE according to the American College of Rheumatology (ACR) 1997 criteria or SLICC 2012 criteria or biopsy proven lupus nephritis with one additional supportive test on at least two occasions (positive Anti-nuclear antibodies (ANA), anti-dsDNA antibodies or anti-Sm antibodies). Presence of moderate to severe periodontitis (at least 30 pockets with Probing depth equal or greater than 5mm). Subject must have voluntarily signed the informed consent. Exclusion Criteria: Pregnancy or breastfeeding. Having fewer than 15 teeth. Subject knowingly has HIV or Hepatitis. Subject is not capable to give informed consent. Presence of concomitant rheumatoid arthritis, Sjogren syndrome, diabetes mellitus. Smoking. Subject on anticoagulants. Subjects on chronic antibiotic therapy or who require antibiotic coverage for periodontal procedures. Subjects who received periodontal treatment within 6 months from the baseline -

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Total 200 Participants for part 1 (baseline). Randomization (Part 2) Control Test group (n=15) control group (n=15)
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: test group<br>intensive periodontal treatment (IPT) | Procedure: supra/sub gingival root surface debridement<br>* The test group will undergo Intensive periodontal treatment (IPT)<br>* Other names: IPT;|
| Sham Comparator: control group<br>Control periodontal treatment (CPT) | Procedure: supra-gingival scaling and polishing<br>* Control group will receive the Control periodontal treatment (CPT).<br>* Other names: CPT;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To measure the effect of periodontal treatment on SLE patients | Endothelial function/dysfunction (vessel wall elasticity) will be observed in the population of SLE patients (30) who will undergo periodontal treatment (before and after) by using Flow mediated dilatation (FMD) which is an ultra-sound scan of brachial artery in visit 2, 4 and 6). | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To measure the effect of PT on biomarkers of SLE disease severity/progression in a population of patients suffering from SLE and PD. | 30 Patients will be recruited and will run a blood test in visit 2, 4 and 6 to observe the CRP (C-reactive Protein) that is an inflammatory marker before and after Periodontal treatment in patients with SLE. | 2 years | 
| To measure the effect of Periodontal Treatment on the B-cell panel in a population of patients suffering from SLE and PD. | Since B-cells (lymphocytes) are already unnaturally high in SLE patients we want to see if Periodontal Treatment decreases the total cell load/population by Flow cytometry with the blood samples taken form the (30) SLE patients in visit 2, 4 and 6. | 2 Years | 
| To measure the effect of Periodontal Treatment on the systemic inflammatory and oxidative profile of a population of patients suffering from SLE and PD. | Because SLE and Periodontal diseases are both chronic inflammatory diseases Nitrous oxide production is raised in both diseases leading to self inflicted tissue damage. Blood will be drawn form the (30) patients with SLE and will run a D-ROM test on the blood samples taken in visit 2, 4 and 6 to observe the oxidative profile of the patients with SLE before and after periodontal treatment. | 2 years | 
| To measure the effect of Periodontal Treatment on skin lesions in a population of patients suffering from SLE and PD. | 30 SLE patients will undergo OCT (Optical coherence tomography) investigation. SLE patients might have skin lesion as an immune destructive response by the cells. OCT will observe the skin lesions caused by the disease (SLE) in visit 2, 4 and 6 (before and after periodontal treatment) | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SLE, Periodontitis, Lupus