New In Situ Model Design for Caries and Erosion
Novel In Situ Caries and ETW Models Development: Safety and Validation Study
This study will test simultaneously and independently two novel in situ models, one for caries and one for erosive tooth wear (ETW), based on the simulation of these dental conditions on enamel specimens placed on 3D-printed mandibular appliances. Caries simulation will be done on the right side (color-coded blue) of the appliance, while ETW on the left side (color-coded red) and their outcomes evaluated independently. The study aims at testing the safety, compliance and F-efficacy (dose-response) of the models. The study will follow a double-blind, single-center, 3-way within-subject crossover design. Treatments will consist of dentifrices, or toothpastes, (1150 ppm F as sodium fluoride, 250 ppm F as sodium fluoride and 0 ppm F/Negative Control) used twice a day.
Studienübersicht
Status
Bedingungen
Detaillierte Beschreibung
The proposed in situ models have been designed for the study of dental caries and ETW, and to overcome some limitations associated to the models used at the Oral Health Research Institute. It is based on the removable intraoral mandibular appliance, to be used by participants with at least 20 teeth in the mouth, and targeting a younger adult population. The construction of the intraoral appliance will take advantage of the recent technology, precision and cost-efficiency associated to intraoral digital scanners and 3D metal printers. Wearing these appliances should be comfortable, as they rest passively in the cheek pouch and do not interfere with the habitual intercuspation of the teeth and phonetics. The investigators hypothesize the proposed in situ caries and ETW models to provide adequate treatment response broadly similar to our established caries and erosion in situ models, while expanding their utility, allowing long-term use and maintaining high subject compliance.
After study screening procedures are complete at the first study visit, a custom removable intraoral mandibular appliance will be made for each participant who is eligible to enroll in the study. Participants may need to return to the research site several times for appliance "try-in" visits prior to beginning the study procedures. Once a comfortable, well fitting appliance has been made, participants will proceed to study procedures.
Participants will progress through three treatment periods (each approximately 21 days in length). Each treatment period will require 5 study visits and at-home study procedures:
- Prior to each treatment period, participants will attend a dental cleaning visit where a dental cleaning and oral examination will occur. At the end of the dental cleaning visit, participants will be provided with a fluoride free toothpaste to use at home for 2-3 days prior to the treatment initiation visit.
- At each treatment initiation visit, 4 tooth specimens will be placed in each side of the intraoral appliance. Impressions will be made and stored for analysis. Participants will be provided with the first assigned toothpaste and at-home supplies.
- During each 21 day treatment period, participants will use one of three study toothpastes, containing different fluoride levels, for the study directed twice daily brushing. Participants will be exposed to all three study toothpastes, however the treatment order sequence will be randomly assigned.
- During each 21 day treatment period, participants will wear the dental appliance 24 hours per day except during meals/snacks and during at-home study directed procedures. Twice daily, participants will remove and brush the appliance according to study-specific directions. Four times daily, participants will remove and complete appliance challenge tasks in which the left and right sides of the appliance will be soaked in different solutions for 5 minutes at a time. Participants will return for evaluation at approximately 7, 14 and 21 days after each treatment period is initiated.
- At the completion of each treatment period, participants will repeat the dental cleaning, treatment initiation, and day 7, 14, and 21 post-treatment initiation visits until all three study toothpastes have been used.
Studientyp
Einschreibung (Tatsächlich)
Phase
- Phase 3
Kontakte und Standorte
Studienorte
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Indiana
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Indianapolis, Indiana, Vereinigte Staaten, 46202
- Oral Health Research Institute of the Indiana University School of Dentistry
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Teilnahmekriterien
Zulassungskriterien
Studienberechtigtes Alter
Akzeptiert gesunde Freiwillige
Studienberechtigte Geschlechter
Beschreibung
Inclusion Criteria:
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In order to participate subjects must:
- Provide voluntary, written informed consent;
- Be between 18 and 65 years old;
- Understand and be willing, able and likely to comply with all study procedures and restrictions;
- Be willing and capable of wearing a custom-made removable mandibular appliance 24 hours a day for three (3), three-week treatment periods;
- Be in good medical and dental health with no active caries or periodontal disease; Note: subjects presenting at screening with caries may continue in the study if their carious lesions are restored prior to beginning treatment 1; and,
- Have a salivary flow rate in the range of normal values (unstimulated whole saliva flow rate ≥ 0.2 mL/min; gum base stimulated whole saliva flow rate ≥ 0.8 mL/min);
- Have an adequate number of teeth and space to accommodate the custom-made removable mandibular appliance, as per the study PI/study dentist's discretion.
Exclusion Criteria:
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No subject may:
- Be pregnant, intending to become pregnant during the study period or breast feeding;
- Have any medical condition that could be expected to interfere with the subject's safety during the study period (including temporomandibular disorders);
- Be taking antibiotics during the study period, or have taken antibiotics in the two weeks prior to the beginning treatment 1;
- Participated in another clinical study or receipt of an investigational drug within 30 days of beginning treatment 1;
- Be taking fluoride supplements, required to use a fluoride mouthrinse or have received a professional fluoride treatment in the two weeks preceding specimen placement; or,
- Have a history of metal allergies.
Studienplan
Wie ist die Studie aufgebaut?
Designdetails
- Hauptzweck: Grundlegende Wissenschaft
- Zuteilung: Zufällig
- Interventionsmodell: Crossover-Aufgabe
- Maskierung: Verdreifachen
Waffen und Interventionen
Teilnehmergruppe / Arm |
Intervention / Behandlung |
|---|---|
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Placebo-Komparator: 0 ppm F toothpaste
Participants will use toothpaste containing 0 ppm fluoride. |
Toothpaste containing 0 ppm fluoride (F) After impressions of both dental arches are taken, a mandibular appliance consisting of a 3D-printed metal frame and acrylic buccal flanges (blue on the right and red on the left) will be made. The appliance will be tested and adjusted for optimal fit and comfort before the experimental phase of the study. At each testing period, 4 gauze-covered 4-millimeter round partially demineralized human enamel specimens will be placed in the right buccal acrylic flange (blue, caries) side of the mandibular appliance and 4 sound human enamel specimens previously mounted on 3 millimeter round metal holders will be placed on the other acrylic flange (red, ETW) side of the same appliance. Subjects will wear their appliance 24 hours a day, except during study procedures, meals/snacks, and drinking (e.g. milk, juice, sports drinks, tea, etc.) except water. |
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Aktiver Komparator: 250 ppm F toothpaste
Participants will use toothpaste containing 250 ppm fluoride. |
After impressions of both dental arches are taken, a mandibular appliance consisting of a 3D-printed metal frame and acrylic buccal flanges (blue on the right and red on the left) will be made. The appliance will be tested and adjusted for optimal fit and comfort before the experimental phase of the study. At each testing period, 4 gauze-covered 4-millimeter round partially demineralized human enamel specimens will be placed in the right buccal acrylic flange (blue, caries) side of the mandibular appliance and 4 sound human enamel specimens previously mounted on 3 millimeter round metal holders will be placed on the other acrylic flange (red, ETW) side of the same appliance. Subjects will wear their appliance 24 hours a day, except during study procedures, meals/snacks, and drinking (e.g. milk, juice, sports drinks, tea, etc.) except water. Toothpaste containing 250 ppm fluoride, as NaF (sodium fluoride) |
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Aktiver Komparator: 1150 ppm F toothpaste
Participants will use toothpaste containing 1150 ppm fluoride. |
After impressions of both dental arches are taken, a mandibular appliance consisting of a 3D-printed metal frame and acrylic buccal flanges (blue on the right and red on the left) will be made. The appliance will be tested and adjusted for optimal fit and comfort before the experimental phase of the study. At each testing period, 4 gauze-covered 4-millimeter round partially demineralized human enamel specimens will be placed in the right buccal acrylic flange (blue, caries) side of the mandibular appliance and 4 sound human enamel specimens previously mounted on 3 millimeter round metal holders will be placed on the other acrylic flange (red, ETW) side of the same appliance. Subjects will wear their appliance 24 hours a day, except during study procedures, meals/snacks, and drinking (e.g. milk, juice, sports drinks, tea, etc.) except water. Marketed toothpaste product containing 1150 ppm fluoride, as NaF (sodium fluoride) |
Was misst die Studie?
Primäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
|---|---|---|
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Mean Percent Surface Microhardness (SMH) Recovery
Zeitfenster: Days 14 and 21 of each of the three consecutive treatment periods (each treatment period is 21 days)
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Description: The SMH test will be used to assess changes in the mineral status of partially demineralized enamel specimens. SMH will be measured using a Wilson 2100 Hardness Tester. The extent of remineralization will be calculated based on the Gelhard et al. method of %SMH recovery = (D1-R)/(D1-B) x 100 where: B = indentation length (µm, micrometer) of sound enamel specimen at baseline D1 = indentation length (µm) after in vitro demineralization R = indentation length (µm) after intra-oral exposure. |
Days 14 and 21 of each of the three consecutive treatment periods (each treatment period is 21 days)
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Surface Loss
Zeitfenster: Days 14 and 21 of each of the three consecutive treatment periods (each treatment period is 21 days)
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Measurements of enamel surface wear respective to the metal holder reference surfaces will be made on impressions of the specimens taken at baseline and after 7, 14 and 21 days of study. The impression of each specimen will be carefully cut with the aid of a scalpel and positioned on the profilometer with double adhesive tape for the scan. The parameters for the scan of both specimens and impressions will consist of step size set at 0.02 mm and number of steps at 200, in both x and y directions. The total area scanned will be 3 mm x 3 mm round specimens. With the use of dedicated software, the depth of the treated area will be calculated based on the reference surfaces. A 3-point height tool will be applied. Profile scans generated from impressions will be inverted (using the software) before analysis, in order to provide outcome data of surface loss (micrometers). |
Days 14 and 21 of each of the three consecutive treatment periods (each treatment period is 21 days)
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Sekundäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
|---|---|---|
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Mean Enamel Fluoride Uptake
Zeitfenster: Days 14 and 21 of each of the three consecutive treatment periods (each treatment period is 21 days)
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The Sakkab et al. microdrill enamel biopsy technique will be used to analyze the fluoride content of the partially demineralized enamel specimens. The amount of fluoride-uptake by enamel will be calculated based on the amount of fluoride divided by the area of the enamel cores and expressed as µg F/cm2. |
Days 14 and 21 of each of the three consecutive treatment periods (each treatment period is 21 days)
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Mean Net Acid Resistance
Zeitfenster: Days 14 and 21 of each of the three consecutive treatment periods (each treatment period is 21 days)
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To test whether the dentifrice imparts acid resistance to the enamel after 14 and 21 days of intra-oral exposure, a second in vitro demineralization will be repeated on the enamel specimens. SMH will be then evaluated by placing 5 indentations 100µm to the right of the indentations placed in situ remineralization. The %NAR will be calculated by the Corpron et al. method of % Net Acid Resistance = [(D1-D2) / (D1-B)] * 100 where: B: Indentation length (µm) of sound enamel at baseline D1: Indentation length (µm) after first in vitro demineralization D2: Indentation length (µm) after second in vitro demineralization |
Days 14 and 21 of each of the three consecutive treatment periods (each treatment period is 21 days)
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Mean Comparative Acid Resistance
Zeitfenster: Days 14 and 21 of each of the three consecutive treatment periods (each treatment period is 21 days)
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This measure takes a different approach to understanding whether the enamel formed during remineralization is more resistant to acid than the original enamel. Using the data from the two enamel specimens, the equation used will compare explicitly the reduction in SMH brought by the first and second acid challenges:
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Days 14 and 21 of each of the three consecutive treatment periods (each treatment period is 21 days)
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Transervse Microradiography (TMR) - Integrated Mineral Loss
Zeitfenster: Days 14 and 21 of each of the three consecutive treatment periods (each treatment period is 21 days)
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Sections, approximately 100 µm in thickness, will be cut parallel to the orientation cut, after completion of the SMH analysis, using a Silverstone-Taylor Hard Tissue Microtome (Scientific Fabrications Laboratories, USA). The sections will be placed in the TMR-D system and X-rayed at 45 kV and 45 mA at a fixed distance for 12 s. An aluminum step wedge will be X-rayed under identical conditions. The digital images will be analyzed using the TMR software v.3.0.0.18. Sound enamel will be assumed to be 87% v/v mineral. Lesions will be analyzed after in situ demineralization to calculate Integrated Mineral Loss (∆Z): [(lesion depth x 87) - area under the curve*]. *Area under the curve which relates volume % mineral at distances from the specimen surface with respect to section thickness. |
Days 14 and 21 of each of the three consecutive treatment periods (each treatment period is 21 days)
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Transverse Microradiography (TMR) - Lesion Depth
Zeitfenster: Days 14 and 21 of each of the three consecutive treatment periods (each treatment period is 21 days)
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Sections, approximately 100 µm in thickness, will be cut parallel to the orientation cut, after completion of the SMH analysis, using a Silverstone-Taylor Hard Tissue Microtome (Scientific Fabrications Laboratories, USA). The sections will be placed in the TMR-D system and X-rayed at 45 kV and 45 mA at a fixed distance for 12 s. An aluminum step wedge will be X-rayed under identical conditions. The digital images will be analyzed using the TMR software v.3.0.0.18. Sound enamel will be assumed to be 87% v/v mineral. Lesions will be analyzed after in situ demineralization to calculate Lesion Depth (L): 83% mineral i.e. 95% of the mineral content of sound enamel. |
Days 14 and 21 of each of the three consecutive treatment periods (each treatment period is 21 days)
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Transverse Microradiography (TMR) - Maximum mineral density at the surface-zone
Zeitfenster: Days 14 and 21 of each of the three consecutive treatment periods (each treatment period is 21 days)
|
Sections, approximately 100 µm in thickness, will be cut parallel to the orientation cut, after completion of the SMH analysis, using a Silverstone-Taylor Hard Tissue Microtome (Scientific Fabrications Laboratories, USA). The sections will be placed in the TMR-D system and X-rayed at 45 kV and 45 mA at a fixed distance for 12 s. An aluminum step wedge will be X-rayed under identical conditions. The digital images will be analyzed using the TMR software v.3.0.0.18. Sound enamel will be assumed to be 87% v/v mineral. Lesions will be analyzed after in situ demineralization to calculate maximum mineral density at the surface-zone (SZmax). |
Days 14 and 21 of each of the three consecutive treatment periods (each treatment period is 21 days)
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Andere Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
|---|---|---|
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Treatment Compliance
Zeitfenster: Day 21 of each of three consecutive treatment periods (each treatment period is 21 days)
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The number of participants demonstrating treatment compliance will be evaluated. Product use compliance will be assessed via the weight of the dispensed and returned test product tubes. The amount of test product used for each study treatment will be compared to daily product usage recorded on the subject's diary. Also, the cariogenic/erosive challenge procedure completed will be assessed and significant discrepancies will be discussed with the study subject, as needed. Subjects who miss 15% or more treatments within the three-week treatment period will be considered non-compliant. The reason for non-compliance will be noted in the subject's study records. |
Day 21 of each of three consecutive treatment periods (each treatment period is 21 days)
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Mitarbeiter und Ermittler
Sponsor
Ermittler
- Hauptermittler: Anderson Hara, DDS, PhD, Indiana University
Publikationen und hilfreiche Links
Studienaufzeichnungsdaten
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Primärer Abschluss (Geschätzt)
Studienabschluss (Geschätzt)
Studienanmeldedaten
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Zuerst eingereicht, das die QC-Kriterien erfüllt hat
Zuerst gepostet (Tatsächlich)
Studienaufzeichnungsaktualisierungen
Letztes Update gepostet (Tatsächlich)
Letztes eingereichtes Update, das die QC-Kriterien erfüllt
Zuletzt verifiziert
Mehr Informationen
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Schlüsselwörter
Zusätzliche relevante MeSH-Bedingungen
Andere Studien-ID-Nummern
- 31100
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