CariesPhase 3NCT03383783

Evaluation of the Fluoride Dose Response of a Modified In Situ Caries Model

A Phase 3 study of Caries, run by Domenick Zero at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Trial summary

The purpose of this study is to evaluate the fluoride dose response of different dentifrice fluoride concentrations - 0, 250, 500 and 1100 ppm fluoride of our existing in situ model involving the use of human enamel specimens placed in the buccal flange area of the subjects partial denture with the modified model… Read more about this study

Who is it for?: Ages 18 to 85 yearsHealthy volunteers can take part
Conditions the study is for: Caries
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 28 participants
Where: 1 siteUnited States
Study dates: 19 Dec 2017to 2 May 2018
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 85 years
All sexes
Healthy volunteers accepted
Adult, Older adult

Who may be able to join

provide voluntary, written informed consent;
be between 18 and 85 years old;
understand and be willing, able and likely to comply with all study procedures and restrictions;
be wearing a removable mandibular partial denture with sufficient room in one posterior buccal flange area to accommodate two enamel specimens (required dimensions 12 × 7 mm) and room on the same side to accommodate two 4 mm round specimens in the buccal surface of two posterior denture teeth;
be willing and capable of wearing their removable partial denture 24 hours a day for four (4), two-week treatment periods;
be willing to allow study personnel to drill specimen sites (as described #4) in their mandibular partial denture;
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.
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).

Who cannot join

currently be pregnant, intending to become pregnant during the study period or breast feeding;
currently have any medical condition that could be expected to interfere with the subject's safety during the study period;
currently be taking antibiotics or have taken antibiotics in the two weeks prior to the beginning treatment 1;
have participated in another clinical study or receipt of an investigational drug within 30 days of beginning treatment 1; or
be taking fluoride supplements, required to use a fluoride mouthrinse or have received a professional fluoride treatment in the two weeks preceding specimen placement;
be taking or have ever taken bisphosphonate drugs (e.g., Fosamax, Actonel and Boniva) for the treatment of osteoporosis;

Trial locations and contacts

1 site in 1 country.

United States1 site

Indiana University School of Dentistry, Oral Health Research Institute
Indianapolis, Indiana, 46202

Other trials in United States

About this study

Read the detailed description

This will be a double blind, single center, 4-way crossover design study involving 34 adult subjects, between the ages of 18 and 85 years. Two to three days before the start of each treatment period the subjects will have their teeth cleaned to remove all accessible plaque and calculus and will be provided with a non-fluoride dentifrice to use until their next visit. At the beginning of each testing period, two gauze-covered 4 × 4 mm partially demineralized human enamel specimens will be placed in the buccal flange area of the subject's mandibular partial denture. In addition, two gauze-covered 4 mm round partially demineralized bovine enamel specimens will be placed in the buccal surface of two posterior denture teeth of the same side of the partial denture. Once specimens are placed, subjects will wear their partial dentures twenty-four hours a day and use their assigned toothpaste twice daily, as instructed, until their next visit. Specimens will be removed after two weeks and the subjects will undergo a four to five day washout period followed by another cleaning and two to three day lead in period. This process will be repeated until all subjects have used all four test products. Changes in the mineral content of the enamel specimens will be assessed using the SMH and TMR. Enamel fluoride uptake (EFU) will be determined using the microdrill enamel biopsy technique. In addition the net acid resistance (NAR) and the comparative acid resistance (CAR) of the remineralized enamel specimens will be determined.

Conditions: Caries
Being tested: 0 ppm F (placebo, negative control), 250 ppm F as NaF (dose-response control), 500 ppm F as NaF (dose-response control), 1100 ppm F as NaF (positive control)
Keywords: Caries

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

0 ppm F (placebo, negative control)Drug
Also called Sensodyne sodium fluoride/silica toothpaste base formulation
Each subject will use this product during one of the four treatment periods in the crossover study design.
250 ppm F as NaF (dose-response control)Drug
Also called Sensodyne sodium fluoride/silica toothpaste base formulation
Each subject will use this product during one of the four treatment periods in the crossover study design.
500 ppm F as NaF (dose-response control)Drug
Also called Sensodyne sodium fluoride/silica toothpaste base formulation
Each subject will use this product during one of the four treatment periods in the crossover study design.
1100 ppm F as NaF (positive control)Drug
Also called Sensodyne sodium fluoride/silica toothpaste base formulation
Each subject will use this product during one of the four treatment periods in the crossover study design.

Study groups in NCT03383783
Study group	Role	What they receive
Treatment Period 1	Other	0 ppm F (placebo, negative control), 250 ppm F as NaF (dose-response control), 500 ppm F as NaF (dose-response control), 1100 ppm F as NaF (positive control) Receives: Drug: 0 ppm F (placebo, negative control); Drug: 250 ppm F as NaF (dose-response control); Drug: 500 ppm F as NaF (dose-response control); Drug: 1100 ppm F as NaF (positive control)
Treatment Period 2	Other	0 ppm F (placebo, negative control), 250 ppm F as NaF (dose-response control), 500 ppm F as NaF (dose-response control), 1100 ppm F as NaF (positive control) Receives: Drug: 0 ppm F (placebo, negative control); Drug: 250 ppm F as NaF (dose-response control); Drug: 500 ppm F as NaF (dose-response control); Drug: 1100 ppm F as NaF (positive control)
Treatment Period 3	Other	0 ppm F (placebo, negative control), 250 ppm F as NaF (dose-response control), 500 ppm F as NaF (dose-response control), 1100 ppm F as NaF (positive control) Receives: Drug: 0 ppm F (placebo, negative control); Drug: 250 ppm F as NaF (dose-response control); Drug: 500 ppm F as NaF (dose-response control); Drug: 1100 ppm F as NaF (positive control)
Treatment Period 4	Other	0 ppm F (placebo, negative control), 250 ppm F as NaF (dose-response control), 500 ppm F as NaF (dose-response control), 1100 ppm F as NaF (positive control) Receives: Drug: 0 ppm F (placebo, negative control); Drug: 250 ppm F as NaF (dose-response control); Drug: 500 ppm F as NaF (dose-response control); Drug: 1100 ppm F as NaF (positive control)

What is being measured

The primary outcome is the main question the study is designed to answer.

Percentage Surface Microhardness Recovery (%SMH)
The extent of remineralization will be calculated based on the method of [Gelhard et al., 1979].
- SMH recovery = (D1-R)/(D1-B) ×100 B = indentation length (µm) of sound enamel specimen at baseline D1 = indentation length (µm) after in vitro demineralization R = indentation length (µm) after intra-oral exposure.
Measured: Enamel specimens will be evaluated after 14 days of intra-oral exposure

Secondary outcomes (6)

Net Acid Resistance (NAR)
The %NAR will be calculated by the method of Corpron [Corpron et al., 1986]:
- Net Acid Resistance = [(D1-D2) / (D1-B)] * 100 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
Measured: Enamel specimens will be evaluated after 14 days of intra-oral exposure
Comparative Acid Resistance (CAR)
Using the data from the four centrally located enamel specimens, the equation used will compare explicitly the reduction in SMH brought by the first and second acid challenges:
- Comparative Acid Resistance = [(D2-R) / (D1-B)] * 100 B= Indentation length (µm) of sound enamel at baseline R= Indentation length (µm) of enamel after in situ remineralization D1= Indentation length (µm) after first in vitro demineralization D2= Indentation length (µm) after second in vitro demineralization
Measured: Enamel specimens will be evaluated after 14 days of intra-oral exposure
Enamel Fluoride Uptake (EFU)
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.
Measured: Enamel specimens will be evaluated after 14 days of intra-oral exposure
Transverse Microradiography (TMR) - Integrated Mineral Loss - ∆Z
Lesions will be analyzed after in situ demineralization and the following three parameters calculated:
1. Integrated Mineral Loss - ∆Z= [(lesion depth x 87) - area under the curve*]
2. Lesion Depth - L (83% mineral i.e. 95% of the mineral content of sound enamel)
3. Maximum mineral density at the surface-zone - SZmax
Measured: Enamel specimens will be evaluated after 14 days of intra-oral exposure
Transverse Microradiography (TMR) - Lesion Depth - L
Lesions will be analyzed after in situ demineralization and the following three parameters calculated:
1. Integrated Mineral Loss - ∆Z= [(lesion depth x 87) - area under the curve*]
2. Lesion Depth - L (83% mineral i.e. 95% of the mineral content of sound enamel)
3. Maximum mineral density at the surface-zone - SZmax
Measured: Enamel specimens will be evaluated after 14 days of intra-oral exposure
Transverse Microradiography (TMR) - Maximum Mineral Density at the Surface-zone
Lesions will be analyzed after in situ demineralization and the following three parameters calculated:
1. Integrated Mineral Loss - ∆Z= [(lesion depth x 87) - area under the curve*]
2. Lesion Depth - L (83% mineral i.e. 95% of the mineral content of sound enamel)
3. Maximum mineral density at the surface-zone - SZmax (arbitrary unit from TMR software)
Measured: Enamel specimens will be evaluated after 14 days of intra-oral exposure

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

19 Dec 20172 May 2018

First posted26 Dec 2017
Study start19 Dec 2017
Primary completion2 May 2018
Study completion2 May 2018

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for CariesStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Other
Allocation: Randomised
Intervention model: Crossover
Masking: Double blind
Who is masked: Investigator, Outcomes assessor
Enrolment: 28 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03383783
Sponsor's protocol ID: 17-I-112
Other IDs: 208705
Status last verified: May 2019
First submitted: 19 Dec 2017
Last updated: 20 May 2019
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 20 May 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Evaluation of the Fluoride Dose Response of a Modified In Situ Caries Model
ClinicalTrials.gov ID: NCT03383783
Acronym / sponsor ID: 17-I-112
Conditions: Caries
Keywords: Caries
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 28 participants (actual)
Lead sponsor: Domenick ZeroUniversity, hospital or other
Collaborators: GlaxoSmithKline
Study start: 19 Dec 2017 (actual)
Primary completion: 2 May 2018 (actual)
Study completion: 2 May 2018 (actual)
First posted: 26 Dec 2017 (actual)
Results: Posted 20 May 2019

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Other
Allocation: Randomised
Intervention model: Crossover
Masking: Double blind (investigator, outcomes assessor)
Number of arms: 4

Arm	Type	Receives
Treatment Period 1	Other	Drug: 0 ppm F (placebo, negative control), Drug: 250 ppm F as NaF (dose-response control), Drug: 500 ppm F as NaF (dose-response control), Drug: 1100 ppm F as NaF (positive control)0 ppm F (placebo, negative control), 250 ppm F as NaF (dose-response control), 500 ppm F as NaF (dose-response control), 1100 ppm F as NaF (positive control)
Treatment Period 2	Other	Drug: 0 ppm F (placebo, negative control), Drug: 250 ppm F as NaF (dose-response control), Drug: 500 ppm F as NaF (dose-response control), Drug: 1100 ppm F as NaF (positive control)0 ppm F (placebo, negative control), 250 ppm F as NaF (dose-response control), 500 ppm F as NaF (dose-response control), 1100 ppm F as NaF (positive control)
Treatment Period 3	Other	Drug: 0 ppm F (placebo, negative control), Drug: 250 ppm F as NaF (dose-response control), Drug: 500 ppm F as NaF (dose-response control), Drug: 1100 ppm F as NaF (positive control)0 ppm F (placebo, negative control), 250 ppm F as NaF (dose-response control), 500 ppm F as NaF (dose-response control), 1100 ppm F as NaF (positive control)
Treatment Period 4	Other	Drug: 0 ppm F (placebo, negative control), Drug: 250 ppm F as NaF (dose-response control), Drug: 500 ppm F as NaF (dose-response control), Drug: 1100 ppm F as NaF (positive control)0 ppm F (placebo, negative control), 250 ppm F as NaF (dose-response control), 500 ppm F as NaF (dose-response control), 1100 ppm F as NaF (positive control)

Who may qualify

Ages: 18 to 85 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult, Older adult

Key inclusion criteria (8 listed)

provide voluntary, written informed consent;
be between 18 and 85 years old;
understand and be willing, able and likely to comply with all study procedures and restrictions;
be wearing a removable mandibular partial denture with sufficient room in one posterior buccal flange area to accommodate two enamel specimens (required dimensions 12 × 7 mm) and room on the same side to accommodate two 4 mm round specimens in the buccal surface of two posterior denture teeth;
be willing and capable of wearing their removable partial denture 24 hours a day for four (4), two-week treatment periods;

Key exclusion criteria (6 listed)

currently be pregnant, intending to become pregnant during the study period or breast feeding;
currently have any medical condition that could be expected to interfere with the subject's safety during the study period;
currently be taking antibiotics or have taken antibiotics in the two weeks prior to the beginning treatment 1;
have participated in another clinical study or receipt of an investigational drug within 30 days of beginning treatment 1; or
be taking fluoride supplements, required to use a fluoride mouthrinse or have received a professional fluoride treatment in the two weeks preceding specimen placement;

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
0 ppm F (placebo, negative control)Also: Sensodyne sodium fluoride/silica toothpaste base formulationEach subject will use this product during one of the four treatment periods in the crossover study design.	Drug	Treatment Period 1, Treatment Period 2, Treatment Period 3, Treatment Period 4
250 ppm F as NaF (dose-response control)Also: Sensodyne sodium fluoride/silica toothpaste base formulationEach subject will use this product during one of the four treatment periods in the crossover study design.	Drug	Treatment Period 1, Treatment Period 2, Treatment Period 3, Treatment Period 4
500 ppm F as NaF (dose-response control)Also: Sensodyne sodium fluoride/silica toothpaste base formulationEach subject will use this product during one of the four treatment periods in the crossover study design.	Drug	Treatment Period 1, Treatment Period 2, Treatment Period 3, Treatment Period 4
1100 ppm F as NaF (positive control)Also: Sensodyne sodium fluoride/silica toothpaste base formulationEach subject will use this product during one of the four treatment periods in the crossover study design.	Drug	Treatment Period 1, Treatment Period 2, Treatment Period 3, Treatment Period 4

Primary outcome

Percentage Surface Microhardness Recovery (%SMH)
Time frame: Enamel specimens will be evaluated after 14 days of intra-oral exposure
The extent of remineralization will be calculated based on the method of [Gelhard et al., 1979]. * SMH recovery = (D1-R)/(D1-B) ×100 B = indentation length (µm) of sound enamel specimen at baseline D1 = indentation length (µm) after in vitro demineralization R = indentation length (µm) after intra-oral exposure.

6 secondary outcomes

Net Acid Resistance (NAR)
Time frame: Enamel specimens will be evaluated after 14 days of intra-oral exposure
Comparative Acid Resistance (CAR)
Time frame: Enamel specimens will be evaluated after 14 days of intra-oral exposure
Enamel Fluoride Uptake (EFU)
Time frame: Enamel specimens will be evaluated after 14 days of intra-oral exposure
Transverse Microradiography (TMR) - Integrated Mineral Loss - ∆Z
Time frame: Enamel specimens will be evaluated after 14 days of intra-oral exposure
Transverse Microradiography (TMR) - Lesion Depth - L
Time frame: Enamel specimens will be evaluated after 14 days of intra-oral exposure
Transverse Microradiography (TMR) - Maximum Mineral Density at the Surface-zone
Time frame: Enamel specimens will be evaluated after 14 days of intra-oral exposure

Results and safety

Results posted to the registry on 20 May 2019, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
All Study Participants	27	25

Primary outcome: Percentage Surface Microhardness Recovery (%SMH)

Time frame: Enamel specimens will be evaluated after 14 days of intra-oral exposure. Mean (95% Confidence Interval). Unit: Percent Surface Microhardness Recovery

Measure	Bovine Specimens 0 Ppm F n = 27	Bovine Specimens 250 Ppm F n = 27	Bovine Specimens 500 Ppm F n = 27	Bovine Specimens 1100 Ppm F n = 27	Human Specimens 0 Ppm F n = 27	Human Specimens 250 Ppm F n = 27	Human Specimens 500 Ppm F n = 27	Human Specimens 1100 Ppm F n = 27
Value	13.96 (8 to 20.29)	30.59 (22.26 to 38.71)	40.74 (31.68 to 50.34)	48.28 (37.15 to 57.86)	7.42 (2.55 to 12.45)	16.27 (10.33 to 22.51)	21.59 (13.67 to 29.64)	26.75 (18.19 to 35.29)

6 secondary outcomes are reported in the full results.

Adverse events

Time frame: Each participant was monitored for a 3 month period.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
0 Ppm F	0 of 27 (0%)	10 of 27 (37%)	0 of 27
250 Ppm F	0 of 27 (0%)	5 of 27 (18.5%)	0 of 27
500 Ppm F	0 of 27 (0%)	6 of 27 (22.2%)	0 of 27
1100 Ppm F	0 of 27 (0%)	5 of 27 (18.5%)	0 of 27
Between Treatment Periods	0 of 27 (0%)	7 of 27 (25.9%)	0 of 27
Prior to Randomization	0 of 28 (0%)	18 of 28 (64.3%)	0 of 28

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 20 May 2019.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Domenick T Zero, DDS, MS principal investigator

Indiana University

Anderson Hara, DDS, PhD principal investigator

Indiana University

Frank Lippert, PhD principal investigator

Indiana University

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study of Caries, run by Domenick Zero at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 20 May 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 20 May 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage Surface Microhardness Recovery (%SMH) (time frame: Enamel specimens will be evaluated after 14 days of intra-oral exposure). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03383783.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 May 2019.