Clinical trial NCT03928080: Diagnostic Accuracy of Rapid Non-clinical Screening Tests for Early Detection of Periodontitis
Official title: Self-detection and Professional Screening Strategies for Early Detection of Periodontitis: Diagnostic Accuracy of Bleeding on Brushing, Salivary Activated Matrix Metalloproteinase-8 (aMMP-8) and CDC/AAP Screening Questionnaire
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Periodontitis
Gingivitis
Keywords: diagnostic accuracy
early detection
self-assessment
periodontitis
Lead sponsor: The European Research Group on Periodontology (ERGOPerio)
Sponsor class: NETWORK
Collaborators: name: The University of Hong Kong
First posted: 2019-04-25
Enrollment: 408
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: OTHER
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: a convenience sample of consecutive untreated subjects seeking dental care at Prince Philip Dental Hospital

Brief summary: Gum disease is the 6th most prevalent disease of mankind. It is a non-communicable non-resolving inflammation; if untreated it leads to tooth loss and inability to chew properly. It is one of the top 80 human disease contributing 3.5 million years lived with disability and the major cause of increasing oral health costs. Addressing this major public health problem requires greater attention to prevention and early detection.

Gum disease cases in the population remain largely undetected because an affected individual does not feel the presence of gum disease and as a consequence people seek attention in the later stages of the disease once tooth loss has occurred.

In this study the investigators will compare different methods of screening for gum disease and compare them against a full professional examination. The investigators hope to be able to propose simple and effective methods for self-assessment that will allow people to suspect the presence of the disease before tooth loss occurs and thus allow early diagnosis and better treatment.

The whole study procedures consist 3 screening tests and the standard clinical examination. The screening tests involves:(1) a screening questionnaire; (2) a saliva test; (3) a toothbrushing test. Thereafter the participants will receive a standard clinical examination which is regarded as the gold standard for diagnosis of gum disease. Results of these tests will be compared with the standard clinical examination to assess the diagnostic accuracy of these tests.

The general aim of this program is to improve early detection of periodontitis in the population using a self-detection approach based on a toothbrush test as an early sign and a self-performed saliva test as a screening test for an individual to seek professional dental care early in the gum disease process.

The general hypothesis is that combining self-assessment of toothbrush test with a saliva test as an assessment of key inflammatory process underlying gum disease will increase the diagnostic accuracy of a screening approach in the population.

Detailed description: Introduction:

Severe periodontitis is the 6th most prevalent disease of mankind. It is a non-communicable non-resolving inflammation and biofilm dysbiosis; if untreated it leads to tooth loss and masticatory dysfunction. It is: i) one of the top 80 human disease contributing 3.5 million years lived with disability, ii) a source of social inequality, iii) together with its major sequel - tooth loss - it is responsible for 88% of lost productivity from oral diseases (estimated at 54 billion USD), and iv) it is the major cause of escalating oral health costs ( 442 billion USD/year) that in advanced economies represent up to 10% of total medical expenses. Addressing this major public health problem requires greater attention to prevention and early detection.

Periodontitis cases in the population remain largely undetected due to lack of knowledge of early warning signs that can be self detected and to the fact that affected individuals adapt to life with increased degrees of disability as the disease progresses from an early stage (stage I) towards increasingly severe and invalidating stages (III-IV). Not unexpectedly, treatment outcomes improve with early detection while costs increase for later diagnosis due to the need for surgical intervention and rehabilitation of the teeth that have been lost. In partnership with the American Academy of Periodontology (AAP), the Centers for Disease Control and Prevention (CDC) in the United states, has validated a questionnaire (CDC/AAP questionnaire) for first step is important but its focus on more advanced disease, while appropriate to address individuals with more advanced disease, while appropriate to address individuals with more advanced disease towards specialist care, is unlikely to produce cost-effective health gains.

Spontaneous gingival bleeding or gingival bleeding upon tooth brushing (BoB) is a key sign of periodontitis with the potential to become a useful sentinel sign for self-detection. Surprisingly little is known about BoB and its relationship to professional assessment and diagnosis. Few studies have shown that it is highly sensitive to detect gingival inflammation but it has low to moderate specificity for periodontitis as it is shared by both gingivitis (superficial gum inflammation) and periodontitis. Its diagnostic performance, however, may be improved by combining it with salivary test able to discriminate between gingivitis and periodontitis. Salivary activated matrix metalloproteinase-8 (aMMP-8) is a biomarker associated with the inflammatory driven destruction of the periodontal ligament and alveolar characteristic of periodontitis; it has been shown to be able to discriminate between gingivitis and periodontitis in a point of care, professional setting.

The general aim of this program is to improve early detection of periodontitis in the population using a self-detection approach based on BoB as a sentinel sign and a consumer version of a point of care aMMP-8 test as a screening test for an individual to seek professional attention early in the periodontitis disease process.

Aims and Hypotheses to be Tested The aims of this diagnostic trial are to assess the diagnostic performance of: i) bleeding on brushing (BoB) as a sentinel sign, ii) salivary aMMP-8 as a biomarker, iii) a validated questionnaire alone and/or in combination for the early detection of periodontitis.

The general hypothesis is that combining self-assessment of a sentinel sign with a biomarker assessment of key inflammatory process underlying periodontitis will increase the diagnostic accuracy of a screening approach in the population.

Plan of Investigation (i) Subjects The study will involve two populations: i) a convenience sample of adult and elderly subjects reporting for oral health care at Prince Philip Dental Hospital and ii) a validation sample drawn from the Hong Kong adult and elderly population.

Study 1. Consecutive patients reporting to Prince Philip Dental Hospital reception clinic (screening and admission clinic) will be invited to participate.

Study 2. A validation sample will be drawn from a population of Hong Kong adult and elderly population in community and primary care settings. Subjects will be invited to participate and will be examined at the Clinical Research Center of the Prince Philip Dental Hospital.

The prevalence of different stages of periodontitis in the population is estimated at 8-12% for stage III-IV periodontitis and 28-32% for stage I-II periodontitis.

A sample size of 332 subjects has been estimated based on previous studies evaluating the area under the receiving operating curve (ROC curve) of the CDC/AAP questionnaire (0.68) and the ability to detect a 0.07 improvement with 80% power and p\<0.05. A total of 400 subjects will be recruited in each trial to compensate for missing data.

(ii) Methods Consenting subjects will be subject to 3 sequential index tests in a specified sequence: i) they will be administered a validated Cantonese version of CDC/AAP questionnaire; ii) subjects will be instructed to perform a 30 second mouthwash with a standard buffer in order to collect a full mouth sample for aMMP-8 analysis. This will be quantitatively assessed with a point of care test. iii) Subjects will then be instructed to brush their teeth for 2 minutes and the obtained slurry (saliva) quantitatively analyzed for the presence of blood with a spectrophotometric test.

Positive CDC/AAP test will be defined based on the pattern of response to 5 questions according to the criteria specified by a previous study.

Positive BoB test will be defined by the subject's identification of traces of blood in the brushing slurry and later validated quantitatively with a spectrophotometric method based on hemoglobin concentrations.

Positive aMMP-8 test for periodontitis will be defined as a concentration of aMMP-8 \> 20 ng/ml as determined with quantitative point of care lateral flow immunoassay.

After completion of the 3 experimental tests, subjects will undergo a full-mouth periodontal examination conducted by a trained and calibrated periodontal specialist who will determine the clinical diagnosis based on the 2017 international classification and case definition of periodontitis and gingivitis.

(iii) Study design Cross sectional diagnostic trial with independent blind comparison of experimental tests with a reference standard (professional diagnosis of periodontitis by a registered specialist in a clinical setting). First trial on a convenience sample of subjects reporting to Prince Philip Dental Hospital for oral health care, validation trial in a representative sample of the Hong Kong population.

Eligibility criteria: Inclusion Criteria:

* Aged 18 and above.
* Having the ability to learn the standard toothbrushing method with artificial intelligence powered toothbrush.
* Ability and willingness to give written informed consent.

Exclusion Criteria:

* Edentulous mouth.
* Pregnant females.
* Having received professional periodontal treatment (other than supragingival cleaning) within the previous 12 months.
* Having received antibiotic medication within the previous 3 months.

Primary outcomes:
measure: Sensitivity measure
timeFrame: 1day
measure: Specificity measure
timeFrame: 1day
measure: The area under the receiver operating characteristic curve (AUC) measure
timeFrame: 1day
measure: The post-test probability measure
timeFrame: 1day
Secondary outcomes:
Other outcomes:
Locations:
city: Hong Kong
country: China
facility: Prince Philip Dental Hospital, the Univerisity of Hong Kong
Study officials:
affiliation: The University of Hong Kong
name: Maurizio Tonetti, DMD,PhD,MMSc
role: PRINCIPAL_INVESTIGATOR
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