Impact of Pycnogenol® on Gingival Inflammation (PINEGIN)

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

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

Study Overview

• Status: Completed
• Conditions: Periodontitis
• Intervention / Treatment: Dietary supplement: Pycnogenol; Dietary supplement: Placebo

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 90
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Germany
  • Wuerzburg, Germany, 97070
    • Dept. of Periodontology, Center for Oral Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 35 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Pycnogenol Group; Professional mechanical plaque removal + Pycnogenol capsule	Dietary supplement: Pycnogenol; daily consumption of a pycnogenol-containing capsule; Other Names: Maritime pine bark extract
Placebo Comparator: Placebo Group; Professional mechanical plaque removal + placebo capsule	Dietary supplement: Placebo; Daily consumption of a placebo capsule

What is the study measuring?

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
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 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
Gingival Index GI	Gingival Index will be recorded visually according to the modification of the original GI.	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 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

Collaborators and Investigators

• Sponsor: Wuerzburg University Hospital
• Collaborators: University of Wuerzburg

Study record dates

Study Major Dates

• Study Start (Actual): March 17, 2022
• Primary Completion (Actual): July 20, 2024
• Study Completion (Actual): July 20, 2024

Study Registration Dates

• First Submitted: December 19, 2022
• First Submitted That Met QC Criteria: March 27, 2023
• First Posted (Actual): March 28, 2023

Study Record Updates

• Last Update Posted (Actual): August 9, 2024
• Last Update Submitted That Met QC Criteria: August 8, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Stomatognathic Diseases; Periodontal Diseases; Mouth Diseases; Gingival Diseases; Periodontitis; Inflammation; Gingivitis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Platelet Aggregation Inhibitors; Immunologic Factors; Protective Agents; Adjuvants, Immunologic; Antioxidants; Pycnogenols
• Other Study ID Numbers: PINEGIN_Protocol 1.7 - 17-7-21

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No