MANTRA: Mechanisms of Acute Inflammation Following Periodontal Treatment
Study Details
Study Description
Brief Summary
Periodontitis (gum disease) is a chronic inflammatory disease linked to a imbalance of oral microbiome. The most usual treatment involves removal of sub and supragingival plaque and calculus othrwise known as Non-surgical periodontal thrapy (NSPT). Ample evidence now indicates that Periodontitis and NSPT are linked to both local and systemic inflammation. This in turn also explains the association between periodontitis and a number of systemic diseases including cardiovascular diseases.
Vascular endothelium (the innermost lining of blood vessels) exerts protective, anti-inflammatory and anti-clotting functions. As the endothelium ages, and is exposed to the damaging effects of traditional cardiovascular risk factors such as elevated blood pressure, serum cholesterol, glucose and cigarette smoking; these protective properties appear diminished, leading to a state of endothelial dysfunction (ED). Understanding the mechanisms of ED in humans could lead to new therapeutic and/or preventive strategies of CV diseases. Sufficient evidence now suggests that Periodontitis and its treatment (removal of sub and supragingival plaque and calculus-periodntal therapy) are linked to endothelial dysfunction. Studies have extensively characterized the time-course of a single session of non surgical periodontal treatment (IPT) associated with a one week acute inflammatory response. This substantial inflammatory response is also associated with ED assessed by flow-mediated dilation (FMD) of the brachial artery at 24 hrs.
Photodynamic therapy (PDT) helps kill the local pathogens, thus preventing their systemic dissemination; which may ultimately reduce the systemic host inflammatory response generated.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
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N/A |
Detailed Description
Periodontitis (gum disease) is a chronic inflammatory disease linked to a imbalance of oral microbiome. The most usual treatment involves removal of sub and supragingival plaque and calculus othrwise known as Non-surgical periodontal thrapy (NSPT). Ample evidence now indicates that Periodontitis and NSPT are linked to both local and systemic inflammation. This in turn also explains the association between periodontitis and a number of systemic diseases including cardiovascular diseases.
Vascular endothelium (the innermost lining of blood vessels) exerts protective, anti-inflammatory and anti-clotting functions. As the endothelium ages, and is exposed to the damaging effects of traditional cardiovascular risk factors such as elevated blood pressure, serum cholesterol, glucose and cigarette smoking; these protective properties appear diminished, leading to a state of endothelial dysfunction (ED). Understanding the mechanisms of ED in humans could lead to new therapeutic and/or preventive strategies of CV diseases. Sufficient evidence now suggests that Periodontitis and its treatment (removal of sub and supragingival plaque and calculus-periodntal therapy) are linked to endothelial dysfunction. Studies have extensively characterized the time-course of a single session of non surgical periodontal treatment (IPT) associated with a one week acute inflammatory response. This substantial inflammatory response is also associated with ED assessed by flow-mediated dilation (FMD) of the brachial artery at 24 hrs.
The efficacy of periodontal therapy is directly related to the ability of treatment to control the infection sustained by gum bacteria. Several chemical agents, such as antiseptic/bacteriostatic liquids, gels or membranes have been added to the conventional periodontal therapy with the view of improving clinical outcomes. The latest evidence advocates the use of lasers to eliminate bacteria in the periodontal pockets. Photodynamic therapy (PDT) is the process of eradication of target cells by reactive oxygen compound produced after activation of a photo-sensitiser by light of appropriate wavelength. Dental lasers used for PDT can be high-level lasers, low-level laser, and diode lasers. PDT used in dentistry for microbial killing, usually involves the use of low-intensity diode laser irradiation along with photosensitises as a means of arresting the anti-microbial activity.
Researchers and clinicians don't fully understand the mechanism underlying the local and systemic pathways involved in the role of periodontal/oral inflammation on systemic health and diseases Based on the evidence that PDT could kill the local pathogens, thus preventing their systemic dissemination; which may ultimately reduce the systemic host inflammatory response generated. The investigators hypothesized that using PDT before NSPT would result in less local and systemic inflammation/ED Understanding the mechanisms of ED in humans could lead to new beneficial and/or preventive strategies for cardio vascular disease.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: IPT+PDT The experimental arm consist of performing IPT in randomly assigning patients to receive local use of photodynamic therapy (PDT). |
Procedure: IPT+PDT
The experimental arm consist of performing IPT in randomly assigning patients to receive local use of photodynamic therapy (PDT).
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| Sham Comparator: ; IPT+Placebo This experimental arm consist of performing IPT in randomly assigning patients to receive sham use of photodynamic therapy(PDT). |
Procedure: IPT+Placebo
IPT+Placebo
|
Outcome Measures
Primary Outcome Measures
- The primary objective of this study is to investigate the efficacy and safety of pre-treatment with photodynamic therapy (PDT) on systemic vascular dysfunction following a single session of non surgical periodontal therapy (IPT) vs. IPT alone. [6 months post intervention]
The primary outcome -Flow-mediated dilatation (an ultra-sound scan)of the brachial artery- at 24 hours between study groups. Vascular dysfunction (vessel wall elasticity) will be observed in the population of periodontitis patients who will undergo IPT with or without photodynamic therapy, by using Flow mediated dilatation (FMD) which is an ultra-sound scan of brachial artery(before and after treatment). Measurements will be done to assess the % change in vessel wall diameter.
Secondary Outcome Measures
- FMD and Pulse wave velocity (PWV) at different time points following treatment between study groups. [6 months post intervention]
FMD and PWV at 0,1, 3, 7 and 180 days following treatment between study groups. Pulse wave velocity (PWV) is a measure of arterial stiffness between to measurement sites. The blood pressure will be measured in two different sites (proximal and distal). The proximal site will be the common carotid artery and the femoral artery for the distal site.
- Evaluate the effect of PDT /IPT on biomarkers of systemic inflammation. [0, 1, 3, 7 and 180 days following treatment.]
Evaluate the effect of PDT /IPT on biomarkers of systemic inflammation (hs-CRP, ICAM-1, VCAM-1, SAA, IL-6, IL-8, IL-10, IL-17A, IL-18, IL-23, IFN- γ, TNF-α-, MCP-1, TPO, ICAM-3, lipidomic(HDL, LDL, TG), glycaemic and oxidative profile (d-ROMs), as well as and markers of endothelial activation (E-Selectin, ICAM-3, P-Selectin, Thrombomodulin) at different time points following treatment between study groups. The values will be determined by changes in mg/L or pg/ml as applicable.
- Evaluate the effect of PDT/IPT on the monocyte subset, monocyte platelet aggregate (MPA) , and circulating endothelial progenitor cells (EPC). [0, 1, 3, 7 and 180 days following treatment.]
Evaluate the effect of PDT/IPT on the monocyte subset, monocyte platelet aggregate (MPA) , and circulating endothelial progenitor cells (EPC) assessed via flow cytometry in a population of patients suffering from periodontitis at different time points following treatment between study groups. The values will be determined by changes in cell count over time.
- Investigate the periodontal clinical parameters following IPT with and without the use of PDT. [6 months post intervention]
Clinical periodontal parameters differences at following PDT+IPT or IPT. Clinical periodontal parameters will be recorded by a single calibrated examiner using a manual University of North Carolina (UNC-15) periodontal probe to see level of gingival margin with reference to a fixed point on the tooth (cementoenamel junction(CEJ)). The measurements will be recorded in millimetres.
- Explore the mechanisms of action of PDT by studying the microbiome and gingival crevicular fluid proteome following IPT. [6 months post intervention]
Dental plaque and gingival crevicular fluid will be collected for further analyses at all time points (specified outcomes will be part of a different protocol). Changes in microbial counts and inflammatory markers like C reactive protein (hs-CRP) will be assessed over time.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Male/Female subject must be 18 years of age or over.
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Affected by periodontitis, with at least 20 sites with PPD>4mm and have at least 20 teeth (excluding wisdom teeth).
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Have voluntarily signed the informed consent.
Exclusion Criteria:
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Presence of any systemic diseases (e.g., diabetes mellitus or cardiovascular, kidney, liver or lung disease).
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Pregnant or breastfeeding.
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Regular use of analgesic or antibiotics within 1 month before entering the study.
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Have untreated gross carious lesions and/or insufficient restorations.
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Allergic to any ingredient in the products provided within the trial as determined by the dental/medical professional monitoring the study.
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Concurrent participation in other clinical studies.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Eastman Dental Hospital | London | United Kingdom |
Sponsors and Collaborators
- University College, London
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- IRAS Project number 279840