Trial document




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  DRKS00004554

Trial Description

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Title

Periodontal treatment and reduction of vascular inflammation in patients with peripheral arterial disease

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Trial Acronym

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URL of the Trial

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Brief Summary in Lay Language

Scientific background: Results of previous studies have demonstrated a positive association between periodontal disease and atherosclerotic vascular disease such as coronary heart disease, stroke and peripheral arterial disease (PAD. Although there is epidemiologic evidence that periodontitis is associated with PAD no randomized, controlled trial has been designed to test the hypothesis that periodontal therapy reduces vascular inflammation in PAD.
Hypothesis: We hypothesize that treatment of periodontitis reduces vascular inflammation as shown by reduced F-fluorodeoxyglucose (FDG) uptake in atherosclerotic plaque of patients with PAD in whole-body positron emission tomography (PET).
Study design: Consecutive patients with PAD will be screened for the presence of periodontitis. Subjects with severe Periodontitis will be invited to participate in the study. Patients will be randomized to the periodonatal therapy group (with or without antibiotic treatment) or to the community dental care group. In the periodontal therapy group non-surgical treatment will be performed. Participants randomized to the community dental care group will be advised to seek the opinion of a dentist after the FDG-PET/CT follow-up examination. FDG-PET/CT will be performed in the periodontal therapy group before and three months after periodontal treatment. In the community dental care group FDG-PET/CT imaging will be performed at baseline and after three months. Thereafter, community dental care will be recommended in a letter stating the tentative diagnosis.
Primary endpoint will be reduction of vascular inflammation. Secondary endpoints will be reduction of cardiovascular biomarkers and data on feasibility including data on compliance, periodontal and cardiovascular outcomes, and adverse events.
Potential prospective impact: The results of our study will elucidate the impact of periodontal therapy on the reduction of vascular inflammation. Since inflammation plays a critical role in atherosclerotic plaque initiation, progression, and disruption, a procedure that reduces vascular inflammation may reduce cardiovascular morbidity and mortality.

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Brief Summary in Scientific Language

Scientific background: At least three meta-analyses have demonstrated a positive association between periodontal disease and atherosclerotic vascular disease such as coronary heart disease, stroke and peripheral arterial disease (PAD). We were able to show that treatment of severe periodontitis reversed endothelial dysfunction accompanied by a significant decrease in C-reactive protein concentrations in otherwise healthy subjects. Although there is epidemiologic evidence that periodontitis is significantly associated with PAD and despite the detection of periodontopathic bacteria in atherosclerotic specimen, no randomized, controlled trial has been designed to test the hypothesis that periodontal therapy reduces vascular inflammation in PAD.

Hypothesis: We hypothesize that treatment of periodontitis reduces cardiovascular biomarkers and vascular inflammation as shown by reduced F-fluorodeoxyglucose (FDG) uptake in atherosclerotic plaque of patients with PAD in whole-body positron emission tomography (PET).

Study design: Consecutive patients with PAD will be screened for the presence of periodontitis. Subjects who meet the inclusion criteria of severe Periodontitis will be invited to participate in the study. Patients will be randomized to the periodonatal therapy group with antibiotic treatment or periodonatal therapy group without antibiotic treatment or to the community dental care group. In the periodontal therapy group non-surgical treatment will be performed with or without systemic antibiotic therapy. Participants randomized to the community dental care group will be advised to seek the opinion of a dentist after the FDG-PET/CT follow-up examination. FDG-PET/CT will be performed in the periodontal therapy group before and three months after periodontal treatment. In the community dental care group FDG-PET/CT imaging will be performed at baseline and after three months. Thereafter, community dental care will be recommended in a letter stating the tentative diagnosis.
Primary endpoint will be reduction of vascular inflammation as measured by target to background ratio (TBR) of PET FDG uptake. Secondary endpoints will be reduction of cardiovascular biomarkers and data on feasibility including data on compliance, periodontal and cardiovascular outcomes, and adverse events.

Potential prospective impact: The results of our study will elucidate the impact of periodontal therapy on the reduction of vascular inflammation. Since inflammation plays a critical role in atherosclerotic plaque initiation, progression, and disruption, a procedure that reduces vascular inflammation may reduce cardiovascular morbidity and mortality.
Amendment I (8.2.13) 1) Implementation of two treatment groups (with/without antibiotic therapy) 2) Assessment of patient's nutritional status and measurement of body composition

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Organizational Data

  •   DRKS00004554
  •   2012/11/28
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  •   yes
  •   Approved
  •   EK 24-456ex 11/12, Ethikkommission der Medizinischen Universität Graz
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Secondary IDs

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Health Condition or Problem studied

  •   I70.2 -  Atherosclerosis of arteries of extremities
  •   K05.3 -  Chronic periodontitis
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Interventions/Observational Groups

  •   Periodontal therapy with antibiotic therapy at the study center (University Dental School). Periodontal therapy usually comprises three sessions within one week.
  •   Periodontal therapy without antibiotic therapy at the study center (University Dental School). Periodontal therapy usually comprises three sessions within one week.
  •   no periodontal therapy for 3 months, thereafter community dental care
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Characteristics

  •   Interventional
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  •   Randomized controlled trial
  •   Open (masking not used)
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  •   Control group receives no treatment
  •   Treatment
  •   Parallel
  •   N/A
  •   N/A
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Primary Outcome

Reduction of vascular inflammation as measured by 18Fluorodeoxyglucose Positron Emission Tomography/CT (FDG-PET/CT) before and 3 months after periodontal treatment

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Secondary Outcome

1) reduction of cardiovascular biomarkers before and 3 months after periodontal therapy:
- high-sensitivity CRP: Immunturbidimetry
- IL-6: ElektroChemiLumineszenzImmunoAssay
- VCAM-1: ELISA (enzyme linked immunosorbent assay)
- ICAM-1: ELISA
- MMP-9: ELISA
- MCP-1: ELISA
- E-selectin: ELISA
- adiponectin: ELISA
- Oxidative/nitrosative stress:
- ADMA: HPLC (high pressure liquid chromatography)
- oxidized-LDL: ELISA
- MPO: ChemiLumineszenzImmunoAssay (Abbott Architect)

2) data on compliance, periodontal outcome-parameter (full mouth plaque score (FMPS) and full mouth bleeding score (FMBS)), cardiovascular outcome-parameter (ancle-brachial index, pulse-wave velocity, flow-mediated dilation) and adverse events will also be measured/evaluated before and 3 months after periodontal therapy.

3) data on patient's nutritional status (Food Frequency Questionaire, malnutrition screening, 24-h dieatary recall) and body composition (iDEXA Scan)

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Countries of Recruitment

  •   Austria
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Locations of Recruitment

  • University Medical Center 
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Recruitment

  •   Actual
  •   2013/04/15
  •   90
  •   Monocenter trial
  •   National
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Inclusion Criteria

  •   Both, male and female
  •   18   Years
  •   99   Years
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Additional Inclusion Criteria

i. Symptomatic PAD
1. PAD Fontaine’s stages II (intermittent claudication) and documented luminal stenosis >70% on ultrasound or angiography
2. PAD Fontaine’s stages III (critical limb ischemia) and documented luminal stenosis >70% on ultrasound or angiography
ii. Severe periodontitis as defined by the presence of at least six natural teeth, including third molars, with at least three teeth with probing depth >4mm; at least two teeth with interproximal clinical attachment loss >2mm; and >10% of sites having bleeding on probing excluding teeth indicated for extraction
iii. Signed informed consent form

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Exclusion Criteria

i. PAD Fontaine’s stage IV (tissue damage/loss)
ii. Life expectancy <6 months
iii. Instable cerebrovascular or cardiovascular disease
iv. Clinically apparent infectious disease (e.g. pneumonia, symptomatic urinary tract infection)
v. Systemic inflammatory disease (e.g. chronic inflammatory bowel disease, rheumatoid arthritis, vasculitis by clinical assessment)
vi. Periodontal treatment within 6 months of the study
vii. Mouth infection other than periodontitis
viii. Uncontrolled diabetes
ix. Pregnancy
x. Age <18 years
xi. Consumption of drugs known to affect periodontal status (anticonvulsants, immunosuppressants)
xii. Allergy to penicillin and/or metronidazole

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Addresses

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    • Klin. Abt. für Angiologie, Medizinische Universität Graz
    • Mr.  ao. Univ.-Prof. Dr.  Gerald  Seinost 
    • Auenbruggerplatz 15
    • 8036  Graz
    • Austria
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    • Klin. Abt. für Angiologie, Medizinische Universität Graz
    • Mr.  ao. Univ.-Prof. Dr.  Gerald  Seinost 
    • Auenbruggerplatz 15
    • 8036  Graz
    • Austria
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    • Klin. Abt. für Angiologie, Medizinische Universität Graz
    • Mr.  ao. Univ.-Prof. Dr.  Gerald  Seinost 
    • Auenbruggerplatz 15
    • 8036  Graz
    • Austria
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Sources of Monetary or Material Support

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    • Fonds zur Förderung der wissenschaftlichen Forschung (FWF)
    • Sensengasse 1
    • A-1090  Wien
    • Austria
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Status

  •   Recruiting complete, follow-up complete
  •   2016/02/26
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Trial Publications, Results and other Documents

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* This entry means the parameter is not applicable or has not been set.