Periodontitis as Signal for an Underlying Disease (PACMEL)

• ClinicalTrials.gov Identifier: NCT03459638
• Recruitment Status: Unknown
• First Posted: March 9, 2018
• Last Update Posted: May 29, 2018
• Sponsor: Academic Centre for Dentistry in Amsterdam
• Collaborators: Labonovum B.V.; Sunstar Suisse S.A.; Netherlands Enterprise Agency
• Information provided by (Responsible Party): W.J. Teeuw, Academic Centre for Dentistry in Amsterdam

Study Description

Brief Summary:

This study investigates the differences between subjects with and without periodontitis in: the prevalence of (pre)diabetes mellitus, the risk of atherosclerotic cardiovascular disease, the prevalence of metabolic syndrome and the risk of obstructive sleep apnea syndrome.

Condition or disease	Intervention/treatment
Diabetes Mellitus; Periodontal Diseases; Cardiovascular Diseases; Obstructive Sleep Apnea Syndrome	Other: Screening for DM, ASCVD, MetS and OSAS

Detailed Description:

Diabetes Mellitus (DM), Atherosclerotic Cardiovascular Disease (ASCVD), Metabolic Syndrome (MetS) and Obstructive Sleep Apnea Syndrome (OSAS) are major health problems. However due to absence of symptoms and/or lack of knowledge, people are often unaware of having DM, ASCVD, MetS or OSAS while early treatment could prevent or stop the progression of these diseases. Therefore risk indicators for early detection of DM, ASCVD, MetS and OSAS are needed and proposed.

Many studies demonstrate the association between oral diseases and DM and/or ASCVD. The most observed chronic oral disease is periodontitis. Periodontitis is a common chronic multifactorial inflammatory disease of the supporting structures of the teeth. DM and ASCVD might, due to their proinflammatory state and alteration of the immune system, contribute to the onset and/or progression of periodontitis. Therefore periodontitis could be considered as an early sign of an underlying vascular and/or metabolic pathology.

Some studies have also reported a positive association between periodontitis and MetS. The MetS prevalence in patients with periodontitis was shown to be higher than controls and MetS showed to be associated with severe periodontitis. The association between periodontitis and OSAS is less established, however there is some evidence to a plausible association between periodontal disease and Obstructive Sleep Apnea (OSA).

Due to the broad overlap of objective biomarkers, in this study, subjects with or without periodontitis will be screened for determining the prevalence of (pre)DM, the 10 year risk of ASCVD, the prevalence of MetS and the risk of OSAS.

The screening will be based on clinical measures, specific blood markers determined by a developed finger stick procedure and three questionnaires.

Notably, a recently published pilot paper from the ACTA periodontology research group presents the feasibility and preliminary results of proposed screening for (pre)DM; 18.1% new DM cases were found among subjects with severe periodontitis, compared to 9.9% in mild/moderate periodontitis and 8.5% in controls.

Objective of the study:

The aim of the proposed study is to screen for (pre)DM, an increased 10 year risk of ASCVD, MetS and a high risk of OSAS in participants with and without periodontitis. Consequently, the dental office will be evaluated as a suitable location for early detection of these diseases.

Study Design

• Study Type: Observational [Patient Registry]
• Estimated Enrollment: 783 participants
• Observational Model: Other
• Time Perspective: Cross-Sectional
• Target Follow-Up Duration: 1 Day
• Official Title: Periodontitis as a Potential Early Risk Indicator for Diabetes Mellitus, Atherosclerotic Cardiovascular Disease, Metabolic Syndrome and Obstructive Sleep Apnea Syndrome
• Actual Study Start Date: March 9, 2018
• Estimated Primary Completion Date: March 9, 2020
• Estimated Study Completion Date: March 13, 2020

Groups and Cohorts

Group/Cohort	Intervention/treatment
Periodontitis; Screening for DM, ASCVD, MetS and OSAS in patients with periodontitis	Other: Screening for DM, ASCVD, MetS and OSAS; Finger stick analysis, questionnaires and clinical measurements
No periodontitis; 'Screening for DM, ASCVD, MetS and OSAS in patients without periodontitis	Other: Screening for DM, ASCVD, MetS and OSAS; Finger stick analysis, questionnaires and clinical measurements

Outcome Measures

Primary Outcome Measures :

1. Prevalence of prediabetes and diabetes (DM) [ Time Frame: 24 months ]
   For DM there is the convenient Haemoglobin A1c (HbA1c) level, which is put forward by the American Diabetes Association (ADA) and International Diabetes Federation (IDF) as indicative of the metabolic state: prediabetes (HbA1c: 39-47 mmol/mol) and diabetes (HbA1c: ≥48 mmol/mol).
2. 10-year-risk of atherosclerotic cardiovascular disease (ASCVD) [ Time Frame: 24 months ]
   For ASCVD there is the "10-year-risk" chart, based on age, gender, total cholesterol, HDL cholesterol (HDL-C), LDL cholesterol (LDL-C), systolic and diastolic blood pressure, smoking, presence of diabetes and rheumatoid arthritis (according to the NHG standards, which are the European Society of Cardiology guidelines modified to the Dutch population). The 10-year risk of death or disease by ASCVD can be: Low = <10%, Middle = 10-20%, High = >20%.
3. Prevalence of metabolic syndrome (MetS) [ Time Frame: 24 months ]
   The diagnostic criteria for MetS are based on the waist circumference (WC), triglycerides (TG), HDL-C, hypertension and dysglycemia (according to the NCEP ATP III). Any 3 of these 5 measures constitute diagnosis of metabolic syndrome. The outcome will be: 1. Absence of MetS (when ≤ 2 measures are met for the criteria of MetS) ; 1. Presence of MetS (when ≥ 3 measures are met for the criteria of MetS).
4. Risk of obstructive sleep apnea syndrome (OSAS) [ Time Frame: 24 months ]
   For OSAS there is the recently developed OSAS risk questionnaire (Philips questionnaire), which scores patients into a low, high or severe risk category of having OSAS.The outcome will be on a percentage scale, varying from 0-100%. The cut-off point for being classified into the low risk category will be 35% and the cutt-of point for the severe risk category is 55%. Between 35 and 55%, participants are classified as high risk for OSAS.

Biospecimen Retention:   Samples Without DNA

Blood is collected with a finger stick analysis

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes
• Sampling Method: Non-Probability Sample

Study Population

: In total 783 patients will be included (261 without periodontitis, 261 with mild/moderate periodontitis and 261 with severe periodontitis) at the Academic Centre for Dentistry Amsterdam (ACTA). The subjects with periodontitis that will be enrolled in this study are referred to the periodontal clinic for diagnosis and treatment of periodontitis. The subjects without periodontitis will be selected among individuals that visit the dental school for regular dental checkups. All subjects will be 18 years and older and are mainly inhabitants from Amsterdam and surrounding areas.

Criteria

Inclusion Criteria:

• In order to be eligible to participate in this study, a subject must meet all of the following criteria:
• Age ≥ 18 years
• (Patient) referred for periodontitis
• (Control) visiting the dental school for regular dental check-up without periodontitis
• Able and willing to give written informed consent and comply with the requirements of the study protocol.

Exclusion Criteria:

• None

Contacts and Locations

Contacts

Contact: Wijnand J. Teeuw, Dr.; +31205980322; w.teeuw@acta.nl

Locations

Netherlands

Academic Centre for Dentistry Amsterdam; Recruiting

Amsterdam, Noord-Holland, Netherlands, 1081 LA

Contact: Wijnand Teeuw, Dr. +31205980322 w.teeuw@acta.nl

Sponsors and Collaborators

Academic Centre for Dentistry in Amsterdam

Labonovum B.V.

Sunstar Suisse S.A.

Netherlands Enterprise Agency

Investigators

• Principal Investigator: Wijnand J. Teeuw, Dr.; Academic Centre for Dentistry Amsterdam

  Study Documents (Full-Text)

Documents provided by W.J. Teeuw, Academic Centre for Dentistry in Amsterdam:

Study Protocol and Statistical Analysis Plan  [PDF] February 12, 2018

More Information

Additional Information:

Publications:

Teeuw WJ, Kosho MX, Poland DC, Gerdes VE, Loos BG. Periodontitis as a possible early sign of diabetes mellitus. BMJ Open Diabetes Res Care. 2017 Jan 19;5(1):e000326. doi: 10.1136/bmjdrc-2016-000326. eCollection 2017.

Nibali L, Tatarakis N, Needleman I, Tu YK, D'Aiuto F, Rizzo M, Donos N. Clinical review: Association between metabolic syndrome and periodontitis: a systematic review and meta-analysis. J Clin Endocrinol Metab. 2013 Mar;98(3):913-20. doi: 10.1210/jc.2012-3552. Epub 2013 Feb 5. Review.

Al-Jewair TS, Al-Jasser R, Almas K. Periodontitis and obstructive sleep apnea's bidirectional relationship: a systematic review and meta-analysis. Sleep Breath. 2015 Dec;19(4):1111-20. doi: 10.1007/s11325-015-1160-8. Epub 2015 Mar 24. Review.

Friedewald VE, Kornman KS, Beck JD, Genco R, Goldfine A, Libby P, Offenbacher S, Ridker PM, Van Dyke TE, Roberts WC; American Journal of Cardiology; Journal of Periodontology. The American Journal of Cardiology and Journal of Periodontology editors' consensus: periodontitis and atherosclerotic cardiovascular disease. J Periodontol. 2009 Jul;80(7):1021-32. doi: 10.1902/jop.2009.097001.

Beukers NG, van der Heijden GJ, van Wijk AJ, Loos BG. Periodontitis is an independent risk indicator for atherosclerotic cardiovascular diseases among 60 174 participants in a large dental school in the Netherlands. J Epidemiol Community Health. 2017 Jan;71(1):37-42. doi: 10.1136/jech-2015-206745. Epub 2016 Aug 8.

• Responsible Party: W.J. Teeuw, Principal Investigator, Academic Centre for Dentistry in Amsterdam
• ClinicalTrials.gov Identifier: NCT03459638
• Other Study ID Numbers: PerioSystemicACTA
• First Posted: March 9, 2018
• Last Update Posted: May 29, 2018
• Last Verified: May 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by W.J. Teeuw, Academic Centre for Dentistry in Amsterdam:

Screening

Additional relevant MeSH terms:

Periodontitis; Periodontal Diseases; Sleep Apnea Syndromes; Sleep Apnea, Obstructive; Cardiovascular Diseases; Diabetes Mellitus; Syndrome; Disease; Pathologic Processes; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Apnea; Respiration Disorders; Respiratory Tract Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases; Mouth Diseases; Stomatognathic Diseases