Caries Lesion Activity in Orthodontic Patients - Calcivis System

Study Overview
=================
Brief Summary
-----------------
This is a prospective, single-centre clinical study to monitor caries lesion activity in orthodontic patients with the Calcivis System over a 12 week period. Dentists will identify patients who have had dental appliances in place for a minimum of 12 months and have visible white spot lesions on the anterior surfaces of incisors and / or canines at de-bond. Following de-bond, images of the tooth surface will be taken with the Calcivis System. Presence or absence of elevated luminescence on the images will indicate activity / inactivity. Only patients with at least one tooth identified as active with the Calcivis System will continue in the study and be followed up at 2, 4, 8 and 12 weeks de-bond. Images of the active teeth will be taken with the Calcivis System as before, at each follow-up visit. The percentage of teeth showing luminescence using the Calcivis System will be calculated and summarised for all subjects for each post-baseline visit, and additionally by Investigator. This will then be summarised over all subjects for each post-baseline visit.

Detailed Description
-----------------
Dental caries (tooth decay) is a significant clinical and public health problem. The development of caries lesions involves a net mineral loss of dental tissue, which can lead to progressive loss of tooth structure and associated pain and disease. Detecting, assessing, diagnosis and treating such lesions are core activities in dentistry. Currently the main detection and diagnosis aids are visual inspection and the used of a probe, together with X-ray images. Determination of the activity status of a lesion (how likely it is to progress) is requires to assess treatment needs. Currently methods are problematic and involve the clinicians' subjective assessment and / or monitoring of lesions progression over a number of visits. It is generally recognised and reported in the dental literature that patients undergoing orthodontic treatment with fixed appliances find it difficult to maintain meticulous oral hygiene and that, as a result, plaque accumulates adjacent to the orthodontic brackets (which are usually placed on the buccal, Free Smooth, surfaces of teeth, which are readily visible) holding the metal wires which are involved in moving the teeth - thus white spot lesions commonly develop at these sites of plaque stagnation. These lesions are, de facto, actively developing during orthodontic treatment, thus represent 'active lesions'. Once the wires and brackets are removed post-treatment, normal oral hygiene can be resumed, the plaque/biofilm over these lesions is readily removed and they become arrested, i.e. the demineralisation process ceases. Thus during a short period of time - a matter of weeks - there is usually a transition from active to inactive status for these 'orthodontically-induced' white spot lesions. By assessing and monitoring these lesions, using the Calcivis device, at relatively short intervals during this period of lesion status transition immediately post orthodontic treatment it would be possible to monitor the reduction in the demineralisation process as these lesions arrest. A previous clinical study on the prototype of the Calcivis System has been conducted. The results concluded that the Calcivis System was safe for use and the level of agreement between elevated luminescence and areas of expected activity was above 70% and not due to chance (NCT02098304). This prospective, single-centre clinical study has been designed to assess the use of the Calcivis System for monitoring the activity levels of post-orthodontic treatment white spot lesions over time. The Dentist will share the images with the patient The device under evaluation comprises a hand-held customized intra-oral camera which takes both black & white and luminescent images of a lesion on a tooth surface while simultaneously applying a photoprotein solution. The photo-protein detects free calcium ions on the tooth surface and produces a light signal if the caries lesion is active. For the study, patients attending routine Orthodontic appointments to have their appliances checked, and who are identified by the Investigator as meeting the Inclusion and Exclusion criteria, and are ready for de-bond, will be approached to discuss their possible participation in the study. Patients will be given a Patient Information Sheet to read and time to consider their participation in the study. If they are happy to participate they will asked to attend for five Study Visits - de-bond (baseline), 2, 4, 8 and 12 weeks. Written informed consent will be taken before any study procedures are conducted. As children under the age of 16 are included in this study, parent / guardian consent will be taken where appropriate. At study Visit 1, demographics, relevant medications, oral hygiene and orthodontic history data will be collected. The orthodontist will carry out an oral examination and the tooth / teeth identified as per inclusion / exclusion criteria, will be cleaned with prophy paste, rinsed with tap water and a 3-in-1 air / water spray before being air dried and staged as per ICDAS coding. Reference intra-oral photographs will be taken of each tooth. The free smooth tooth surfaces will again be air dried before taking the black & white and luminescent images with the Calcivis System. After imaging is completed, patients rinse out with tap water. Adverse event will be collected throughout. The dentist will then share the images of the teeth with the patient. Post imaging questionnaires will be completed by each patient at the end of Study Visit 1 and user questionnaires completed by the dental team at the end of each Study Visit 1 day. Only patients who have 'active' lesions on de-bond, as confirmed with the Calcivis System at the baseline visit, will be followed up in this study. If all lesions are assessed as 'inactive', the patient will be withdrawn from the study Eligible patients will return for Study Visits at 2, 4, 8 and 12 weeks post-de-bond. At each of these visits, following a reference photograph of the teeth, each tooth which was active at Study Visit 1 will again be imaged with the Calcivis System as described above and the images shared with the patient. In addition, both Patient and User Questionnaires will be completed at the final Study Visit at 12 weeks.

Official Title
-----------------
Monitoring of Caries Lesion Activity in Orthodontic Patients With the Calcivis System

Conditions
-----------------
Dental Caries

Intervention / Treatment
-----------------
* Device: Calcivis System


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patient must be ≥ 12 years old Patient must have had orthodontic appliances placed on the upper incisors and / or canines for at least 12 months, and be ready for de-bond Patient must have at least one, active white spot lesion identified by the Calcivs System immediately post de-bond Patient and / or parent or guardian must be willing and able to give written informed consent Patient and / or parent or guardian must be willing and able to adhere to study schedule Exclusion Criteria: Any Patient with recent tooth bleaching (within previous two weeks of imaging with the Calcivis System) or within the follow-up period Any patient currently taking part in a clinical research study, or who has taken part in a clinical research study in the previous three months Pregnant and / or nursing mothers

Ages Eligible for Study
-----------------
Minimum Age: 12 Years
Maximum Age: 100 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Active post-othodontic lesions<br>Imaging with the Calcivis System | Device: Calcivis System<br>* Following de-bond, and identification of active post-orthodontic white spot lesions at baseline with the Calcivis System, each active tooth will be again be imaged at 2, 4, 8 and 12 weeks. Both black & white and luminescent images images of the teeth are taken. The images of each tooth are overlaid and a resulting demineralization map of the tooth produced, indicating areas of elevated bioluminescence corresponding to free calcium ions on the surface of the tooth (active caries)<br>* Other names: Calcivis Caries Activity Imaging System;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Presence or Absence of Elevated Luminescence | Percentage of active teeth showing luminescence (as measured by Calcivis System imaging) over time | 0, 2, 4, 8 and 12 weeks | 
| Presence or Absence of Elevated Luminescence | Percentage of active teeth showing luminescence (as measured by Calcivis System imaging) over time, per Investigator | 0, 2, 4, 8 and 12 weeks post de-bond | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Non-patient Related Adverse Events With the Calcivis System | All adverse events and device deficiencies were collected throughout the study on Adverse Event Forms | 0 days, 2, 4, 8 and 12 weeks | 
| Patient Experience | Completion of Patient Questionnaires after imaging with the Calcivis System | Baseline | 
| Patient Experience | Completion of Patient Questionnaires after imaging with the Calcivis System at patient's final visit | Final Visit - either 8 or 12 weeks post debond | 
| User Questionnaires | Completion of User Questionnaires after imaging with the Calcivis System | Baseline visit | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Caries, Acitivity, Demineralsiation