Impact of Pycnogenol® on Gingival Inflammation

Study Overview
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Brief Summary
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This randomized, double-blind, placebo-controlled 2-arm, parallel group clinical trial is designed to evaluate the impact of the regular consumption of a polyphenol-containing Maritime Pine (Pinus pinaster) bark extract (Pycnogenol®) on clinical signs of gingival inflammation in a cohort of periodontal aftercare patients

Detailed Description
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Polyphenols are natural compounds produced by plants that have various functions, such as defence against microbial pathogens or protection against UV light. Based on their antioxidant activity, a soothing or preventive effect of polyphenols on various inflammatory diseases has been suspected. There is evidence of an anti-inflammatory effect of polyphenols in manifest periodontitis as well as antibacterial properties of these compounds. In addition, it is discussed that dietary polyphenols intervene in mechanisms involved in the pathophysiology of arteriosclerotic changes and their progression. This randomized, double-blind, placebo-controlled 2-arm, parallel group clinical trial is designed to evaluate the impact of the regular consumption of a polyphenol-containing Maritime Pine (Pinus pinaster) bark extract (Pycnogenol®) on clinical signs of gingival inflammation in a cohort of periodontal aftercare patients

Official Title
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Impact of a Dietary Supplementation With Maritime Pine Bark Extract (Pycnogenol®) on Gingival Inflammation - a Randomized Clinical Trial (PINEGIN)

Conditions
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Periodontitis

Intervention / Treatment
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* Dietary Supplement: Pycnogenol
* Dietary Supplement: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: number of teeth ≥ 10 age ≥ 35 ≤ 90 years body mass index (BMI) ≥ 20 ≤ 30 history of periodontal disease and inclusion in a regular scheme of supportive periodontal therapy (regularly repeated subgingival biofilm removal 2-4 x/year) minimum of 10% probing sites displaying bleeding on probing Exclusion Criteria: manifestation of inflammatory oral mucosal diseases other than gingivitis xerostomia (stimulated salivary flow ≤ 0.1 ml/minute) inability to perform regular oral home care inability to follow the study protocol due to intellectual or physical handicaps history of malignancy, radiotherapy, or chemotherapy for malignancy in the past 5 years current pregnancy acute infections such as HIV manifestation of metabolic bone disease use of antibiotics and/or anti-inflammatory medications within 4 weeks prior to screening. current orthodontic therapy

Ages Eligible for Study
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Minimum Age: 35 Years
Maximum Age: 90 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: randomized, double-blind, placebo-controlled 2-arm, parallel group clinical trial
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Pycnogenol Group<br>Professional mechanical plaque removal + Pycnogenol capsule | Dietary Supplement: Pycnogenol<br>* daily consumption of a pycnogenol-containing capsule<br>* Other names: Maritime pine bark extract;|
| Placebo Comparator: Placebo Group<br>Professional mechanical plaque removal + placebo capsule | Dietary Supplement: Placebo<br>* Daily consumption of a placebo capsule<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bleeding on Probing (BoP) | Bleeding on Probing (BoP) is defined as the appearance of a bleeding spot within 30 seconds after gently probing the evaluated periodontal pocket by inserting the periodontal probe up to the probable bottom of the pocket. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Gingival Index GI | Gingival Index will be recorded visually according to the modification of the original GI. | 6 months | 
| Plaque Control Record (PlaCR) | Plaque Control Record (PlaCR) is defined as the percentage of assessed supragingival tooth surfaces covered by bacterial plaque. The presence of bacterial plaque is visually assessed after staining the tooth surfaces with a plaque staining agent. | 6 months | 
| Compositional changes within the intestinal microbiota | Compositional changes within the intestinal microbiota between baseline and end of the study are assessed by Next Generation Whole Genome Sequencing on a species level | 6 months | 
| Compositional changes within the oral microbiota | Compositional changes within the oral microbiota between baseline and end of the study are assessed by Next Generation Whole Genome Sequencing on a species level | 6 months | 
| Change in periodontally inflamed surface area (PISA) | PISA is calculated using the recorded pocket depths and bleeding on probing scores at each evaluated tooth at baseline and at the end of the trial at 6 months. | 6 months | 
| Change in salivary polyphenol concentration | Saliva samples for the analysis of salivary polyphenols levels are taken at baseline and at 3 months | 3 months | 
| Change in polyphenol serum concentration | Blood samples for the analysis of polyphenol serum levels are taken at baseline and at 3 months | 3 months | 
| Change in salivary levels of cytokines, cytokine inhibitors, matrix metalloproteinases and MMP inhibitors | Saliva samples are taken at baseline and at the end of the study at 6 months for the analysis of salivary interleukin (IL) 1ß, IL-6, IL-8, IL-31, matrix metalloproteinase (MMP)-8, MMP-9, tissue inhibitor of metalloproteinase (TIMP)-1 and Histatin 5 levels. | 6 months | 
| Change in serum levels of cytokines, cytokine inhibitors, matrix metalloproteinases and MMP inhibitors | Blood samples are taken at baseline and at the end of the study at 6 months for the analysis of serum interleukin (IL) 1ß, IL-6, IL-8, IL-31, matrix metalloproteinase (MMP)-8, MMP-9, and tissue inhibitor of metalloproteinase (TIMP)-1 levels. | 6 months | 
| Change in pulse wave velocity | Pulse wave velocity (m/sec) is measured at baseline and at 3 months | 3 months | 
| Change in central aortal pulse pressure | Central aortal pulse pressure (mmHg) is measured at baseline and at 3 months | 3 months | 
| Change in peripheral systolic and diastolic blood pressure | Peripheral systolic and diastolic blood pressure (mmHg) is measured at baseline and at 3 months. | 3 months |