- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03078595
Gingival Bleeding and Von Willebrand Disease Typ 2 and 3
Is Gingival Bleeding a Symptom of Patients With Type 2 and 3 Von Willebrand Disease? A Case-Control Study
Study Overview
Status
Conditions
Detailed Description
Patients
All patients with type 2 and 3 VWD consecutively consulting the Haemophilia Centre, Medical Clinic III/Institute for Transfusion medicine, Hospital of the Johann Wolfgang Goethe-University Frankfurt/Main are asked to participate in this study as cases. They are asked for bleeding and subjective symptoms indicating periodontal disease.
The study complies with the rules of the Declaration of Helsinki and was approved by the Institutional Review Board for Human Studies of the Medical Faculty of the Goethe-University Frankfurt/Main (Application# 143/15). All participating individuals are informed on risks and benefits as well as the procedures of the study and give written informed consent.
Controls
For each case (VWD) a respective hematologically healthy control is recruited from the gingivitis and periodontitis patients of the Department of Periodontology, Centre for Dentistry and Oral Medicine (Carolinum), Johann Wolfgang Goethe-University Frankfurt/Main. Each control is matched to one of the respective cases for sex, age (±5 years), self-reported smoking status (current smoker/non-smoker), number of remaining teeth (±2 teeth), and periodontal diagnosis (gingivitis, chronic or aggressive periodontitis).
All participants are asked about current and past cigarette smoking habits. Patients who report smoking or have quit smoking for less than five years are classified as smokers. Additionally the amount of carbon monoxide (CO) in exhaled air is measured using a device (Bedfont Smokerlyzer; Bedfont Scientific Ltd, Rochester, Great Britain).
Hematologic examinations
20 ml of blood are sampled from an arm vein. The following data are assessed at the Haemophilia Centre for clinical routine during VWD patient care and due to study design in the controls:
- von Willebrand parameters (VWF antigen [VWF:Ag], Ristocetin cofactor [VWF:RCo], coagulation factor VIII [FVIII:C])
- Current medication if any VWF:Ag and VWF:RCo were measured turbidimetrically using a device (BCS, Siemens, Marburg, Germany). FVIII:C was assessed with specific agents on a coagulation analyser (ACL-300®, Instrumentation Laboratory, Kirchheim, Germany).
Periodontal examinations
The following clinical parameters are assessed at 6 sites per tooth (mesiobuccal, buccal, distobuccal, mesiolingual, lingual, distolingual):
- modified Gingival Bleeding Index (GBI)
- modified Plaque Control Record (PCR)
- PPD and recession to the nearest 0.2 mm using an electronic probe (Florida Probe, Version 3.2, Gainesville, USA). Recession is assessed from the cemento-enamel junction (CEJ) to the gingival margin. At sites where the CEJ was destroyed by restorations the restoration margin (RM) is used as reference. At sites where the CEJ or RM is located apically from the gingival margin the value for recession is negative
- Bleeding on probing (BOP) recorded as positive when bleeding occurs within 30 seconds from probing. For each patient a BOP index is calculated providing the amount of sites with positive BOP in % per patient.
Attachment loss (PAL-V) is calculated as sum of PPD and recession.
All individuals are classified into the following diagnoses:
- plaque-induced gingivitis (PPD < 3.6 mm; PAL-V ≤ 2 mm),
- generalized mild, localized moderate chronic periodontitis (PPD ≥ 3.6 mm; vertical probing attachment level [PAL-V] 3 to 4 mm ≤ 30% of sites; 1 to 2 mm > 30% of sites),
- generalized mild, localized severe chronic periodontitis (PPD ≥ 3.6 mm; PAL-V ≥ 5 mm ≤ 30% of sites; 1 to 2 mm > 30% of sites)
- generalised moderate chronic periodontitis (PPD ≥ 3.6 mm; PAL-V 3 to 4 mm > 30%)
- generalised moderate localised severe chronic periodontitis (PPD ≥ 3.6 mm; PAL-V 3 to 4 mm > 30%; ≥ 5 mm ≤ 30%)
In all individuals hematological and periodontal examinations are obtained within 24 hours. After dental and periodontal examination all patients receive oral hygiene instructions and professional tooth cleaning. In cases of untreated periodontal disease periodontal treatment is offered. VWD are asked to report any bleeding complications after periodontal probing and professional tooth cleaning.
Statistical analysis
The individual patient is used as statistical unit. All analyses are performed on patient level. GBI is defined as the main outcome variable and BOP as secondary outcome variable. All other parameters are control variables. Up to now there are no studies comparing GBI or BOP between VWD type 2 and 3 cases and hematologically healthy controls and there are no standard deviations of mean GBI and BOP for cases and controls. To detect a clinically relevant inter-group difference of 4% GBI or BOP with a type 1 error alpha < 0.05 and a test power of 80% with a standard deviation of group means of 5.5% a sample size of at least 31 individuals is required per group. Thus, it was decided to recruit 31 VWD cases and respectively matched 31 controls.
For all individuals, cigarette pack years are calculated. Group frequencies (VWD, control) are expressed for sex, current smoking. Group means and standard deviations are calculated for GBI, BOP, age, number of remaining teeth, pack years, CO, PCR, VWF:Ag, VWF:RCO, FVIII:C. Further, for each individual the following variables are calculated to describe the periodontal status:
- Mean±standard deviation of PPD and PAL-V
- Percentage of PPD < 4 mm, 4 to 6.8 mm, ≥ 7 mm
- Sum of all PPD, i.e. the sum of the PPD measured at all sites within a patient
- Sum of all PPD with BOP, ), i.e. the sum of the PPD measured at all sites exhibiting BOP within a patient
- Periodontal inflamed surface area (PISA). For each patient PPD were entered into an Excel sheet that can be downloaded freely (http://www.parsprototo.info/pisa.html).
From these group means and standard deviations are calculated. Comparisons between groups for dichotomous parameters are made by χ² or Fisher's exact test and for all other parameters by Mann-Whitney-U test. A post-hoc analysis is performed to estimate the test power that would be required to find a clinically relevant inter-group difference (δ) of 5% for GBI and BOP index with a type 1 error (α) of 0.05 for the actual sample size.
Using stepwise linear backward multiple regression analysis, factors shall be identified that influence GBI and BOP. The following independent variables are entered into the model for GBI: group (VWD/control), sex, age, number of remaining teeth, PCR, CO, pack years, PISA. The following independent variables are entered into the model for BOP: group (VWD/control), sex, age, number of remaining teeth, PCR, CO, pack years, PISA. Due to the fact that mean PPD is mathematically coupled to sum of PPD, sum of PPD with BOP, and PISA these 4 variables are not entered into the regression model at the same time. PISA provides the best representation of the subgingival inflamed area. Thus, PISA is chosen for the final model. The following parameters are described by dummy variables: group (control = 0, VWD = 1), sex (male = 0, female = 1), smoking status (never and former smoker = 0, current smoker = 1). All factors with p < 0.1 are kept in the models. For statistical analysis a PC program is used (SystatTM for Windows Version 12, Systat Inc., Evanston, USA).
Study Type
Enrollment (Actual)
Contacts and Locations
Study Locations
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Frankfurt am Main, Germany, 60590
- Dept. of Periodontology, Center of Dentistry and Oral Medicine, Johann Wolfgang Goethe-University
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Hessen
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Frankfurt am Main, Hessen, Germany, 60596
- Center for Dentistry and Oral Medicine (Carolinum), Johann Wolfgang Goethe-University
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Sampling Method
Study Population
Description
Inclusion Criteria von Willebrand Patients:
- 18 - 80 years old
- no other bleeding disorder except 2 and 3 von Willebrand disease
Inclusion Criteria healthy controls:
- no bleeding disorder
- no anticoagulative medication
Exclusion Criteria von Willebrand Patients:
- requirement of systemic antibiotics for measures that may cause transitory bacteraemia
Exclusion Criteria healthy controls:
- bleeding disorder
Study Plan
How is the study designed?
Design Details
- Observational Models: Case-Control
- Time Perspectives: Cross-Sectional
Cohorts and Interventions
Group / Cohort |
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von Willebrand disease type 2 and 3
Examinations (haematologically and periodontally) of von Willebrand disease patients with type 2 and 3 and healthy controls to evaluate whether type 2 and 3 VWD determines an increased susceptibility to gingival bleeding in response to the oral biofilm
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controls
For each case (VWD) a respective haematologically healthy control is recruited from the gingivitis and periodontitis patients of the Department of Periodontology, Centre for Dentistry and Oral Medicine (Carolinum), Johann Wolfgang Goethe-University Frankfurt/Main.
Each control is matched to one of the respective cases for sex, age (±5 years), self-reported smoking status (current smoker/non-smoker), number of remaining teeth (±2 teeth), and periodontal diagnosis (gingivitis, chronic or aggressive periodontitis).
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Bleeding on Probing (BOP)
Time Frame: cross-sectional: only one assessment at the time of examination
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Using a periodontal probe probing pocket depths (PPD) are assessed with a force of 0.2 N at 6 sites per tooth (mesio-buccal, buccal, disto-buccal, disto-oral, oral, mesio-oral).
After 30 seconds bleeding on probing is scored at each site.
The frequency of bleeding sites of the total number of assessed sites is calculated as index.
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cross-sectional: only one assessment at the time of examination
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Gingival Bleeding Index (GBI)
Time Frame: cross-sectional: only one assessment at the time of examination
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A periodontal probe is gently moved through the gingival sulcus.
Bleeding is assessed at 6 sites per tooth (mesio-buccal, buccal, disto-buccal, disto-oral, oral, mesio-oral).
The frequency of bleeding sites of the total number of assessed sites is calculated as index.
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cross-sectional: only one assessment at the time of examination
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Collaborators and Investigators
Sponsor
Investigators
- Study Chair: Peter Eickholz, Prof., Dept. of Perio, Center for Dent. and Oral Med., JWG-University Frankfurt
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Pathologic Processes
- Hematologic Diseases
- Blood Coagulation Disorders, Inherited
- Coagulation Protein Disorders
- Hemorrhagic Disorders
- Genetic Diseases, Inborn
- Stomatognathic Diseases
- Periodontal Diseases
- Mouth Diseases
- Gingival Diseases
- Blood Coagulation Disorders
- Blood Platelet Disorders
- Oral Hemorrhage
- Hemorrhage
- Von Willebrand Diseases
- Gingival Hemorrhage
Other Study ID Numbers
- 143/15
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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