Periodontitis Clinical Trial
Official title:
Effects of Non-Surgical Periodontal Therapy on Endothelial Function A Randomized Controlled Clinical Trial
The hypothesis of the existence of a causal association between the systemic
infectious/inflammatory burden represented by periodontitis and endothelial function
assessed by flow mediated dilatation of the brachial artery (FMD) is the subject of the
proposed investigation.
The objective of this randomized controlled clinical trial is to evaluate the effects of
periodontal therapy on endothelial function assessed by Flow mediated dilatation (FMD).
The rationale for this project is twofold:
- Establish the extent of acute systemic inflammation and endothelial dysfunction
associated with the delivery of subgingival instrumentation for the treatment of
chronic periodontitis
- Establish whether or not improved control of chronic periodontal infections results in
improved endothelial function and thus the existence of a causal association between
periodontitis and endothelial dysfunction.
In the last decade considerable evidence has supported the hypothesis that chronic low-grade
infections, periodontitis included, and the inflammatory responses associated with them may
play a significant role in the onset of atherosclerosis. An inflammatory alteration of the
normal endothelial activity is thought to be one of the mechanisms that may link infection
with atherosclerosis. It consists of loss of the normal vasodilation, antiplatelet and
antithrombotic properties of the vascular walls and it is frequently called endothelial
dysfunction. Impaired endothelium-dependent dilatation, an early functional marker of
endothelial dysfunction has been demonstrated in young populations with family history of
cardiovascular diseases. In the past 15 years a new non invasive and reproducible technique
called Flow mediated dilatation (FMD) has been used to assess endothelial function.
Periodontitis is a chronic infection of the tooth supporting apparatus caused primarily by
anaerobic gram negative bacteria organised in a biofilm (commonly known as sub-gingival
dental plaque); it leads to inflammatory destruction of the periodontal ligament and
alveolar bone and eventually to tooth exfoliation. Periodontitis is highly prevalent in both
industrialised and developing countries with 10-15% of the adult population being affected
by severe forms of this disease. Recognized risk factors include genetic polymorphisms in
inflammatory genes, environmental exposures such as cigarette smoking, and systemic diseases
such as diabetes. Local periodontal production of prostaglandins and pro-inflammatory
cytokines has been associated with activation of matrix metalloproteinases and eventually to
destruction of the periodontal ligament and alveolar bone. It is the primary cause of tooth
loss in adult populations and as such leads to long term disability and increased treatment
needs.
Local periodontal infections have been associated with a systemic response characterized by
increased serum levels of C-reactive protein (CRP), hyper-fibrinogenemia, moderate
leukocytosis, as well as increased serum levels of IL-1 and IL-6 when compared with
unaffected control populations.
Several epidemiological studies have associated increased levels of acute phase markers with
higher risk for cardiovascular atherosclerotic events. Among these markers, C-reactive
protein is considered to be one of the most sensitive and probably to be an independent risk
factor of atherosclerosis. It is produced by the liver presumably for adaptive or defensive
reasons in response to a variety of inflammatory stimuli, including chronic low grade
infections.
In a recently completed pilot trial we have been able to establish that treatment of
periodontal infections resulted in a significant decrease in serum CRP. In that study,
treatment of periodontal infections led to a significant decrease in serum CRP (0.5 mg/L,
95% CI 0.4 to 0.7 mg/L) and IL6 in otherwise healthy individuals affected with severe,
generalized periodontitis and indicated that periodontitis contributed to the systemic
inflammatory responses.
The treatment associated decrease in systemic inflammatory markers observed in this study
supports the hypothesis that periodontal infections, along with chronic low grade infections
in other body districts, contribute to the inflammatory burden of an individual and may play
a contributory etiologic role in atherosclerosis. It remains to be established whether or
not the observed improvements in serum CRP have an impact on functional vascular parameters
and endothelial function/dysfunction.
The relationship between periodontal treatment and changes in serum CRP is likely to be
bimodal: an increase associated with the delivery of the standard subgingival
instrumentation and the associated bacteremia and tissue damage is expected shortly after
treatment is delivered.
Preliminary trials from our group aimed at the establishment of the pattern of CRP changes
in the first days following delivery of periodontal therapy. The data indicate that serum
CRP levels sharply increase after treatment but that values tend to return to baseline
levels by one week. This bimodal pattern of changes in serum CRP levels is important since
previous investigations have established links between functional vascular parameters such
as flow mediated dilatation (FMD) and serum markers of systemic inflammation such as CRP.
Periodontal therapy therefore may lead to an initial improve FMD parameters in subject were
periodontitis contributes to systemic inflammation and atherosclerosis. The hypothesis of
the existence of a causal association between the systemic infectious/inflammatory burden
represented by periodontitis and endothelial function assessed by FMD is the subject of the
proposed investigation.
Compare the effects of an intensive periodontal treatment regimen with a community based
periodontal care approach in terms of changes in:
- Flow mediated dilatation of the brachial artery (primary outcome)
- Acute phase response in serum (CRP, IL-6,fibrinogen)
- Clinical periodontal parameters: PI, BoP, PPD (CAL)
- Presence of periodontal pathogens in the periodontal pockets before and after treatment
- Patient perception and adverse events associated with the treatment experience This
will be a randomized controlled clinical trial. Its design will be parallel arm, single
blind; outcomes will be evaluated over a 6 months period and will include approximately
120 subjects. Two interventions will be compared: test treatment will be an intensive
regimen of periodontal therapy consisting of oral hygiene instructions and subgingival
debridement delivered at two appointments over a 24 hour period; control treatment will
consist of a community based periodontal care approach consisting of supragingival
removal of deposits delivered at two appointments over a 24 hour period. The control
group will receive the intensive regimen upon completion of the study or upon evidence
that periodontitis is progressing. Subjects with moderate to severe periodontitis will
be recruited among those referred for care to the Periodontal Clinic of the Eastman
Dental Hospital. The primary outcome measure of this study will be changes in Flow
Mediated Dilatation (FMD) of the brachial artery. Secondary outcomes will include
changes in serum CRP and plasma fibrinogen. Periodontal, microbiological and subjective
outcomes will be evaluated as control outcomes. The primary and the secondary outcome
variables will be evaluated before treatment and at 1 day, 7 days, 2 months and 6
months following completion of treatment. Subjects will be randomized to treatment
stratifying for smoking status by a study registrar. Treatment allocation will be
concealed to study personnel by using opaque envelopes and to the examiner by making
treatment records unavailable. All laboratory and FMD analyses will be performed by
unrelated study personnel blind with respect to treatment allocation or stage of
progression of the trial. Intent to treat analyses will be performed by a statistician
blind with respect to treatment allocation.
;
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Treatment
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