Clinical Study of Tooth Enamel Remineralization Using DoReMin Product
Phase: NA
Conditions: White Spot Lesion
Sponsor: Ivoclar Vivadent AG

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Clinical study of tooth enamel remineralization 
using an experimental remineralization product 
 
PROTOCOL 
Clinical Investigation Plan (CIP) - Clinical study of tooth enamel 
remineralization using an experimental remineralization product 
 
Study Title 
Clinical study of tooth enamel remineralization using an 
experimental remineralization product 
Registration 
NCT06166849 
(www.clinicaltrials.gov) 
Study-ID 
IVAG-Study-ID: LL4003223 
EC-Study-ID: "3DM" and "7TP" 
NCA-Study-ID: "DM 3908E" 
Product 
Experimental Fluoride Product 
Document-ID 
LL4182693 
Document Version 
2.0 
Document Date 
24.10.2023 
 
Document Control 
Name 
Principal Investigator: 
Dr. Ada Delean, Discipline of Odontology, Endodontics and Oral Pathology, University of 
Medicine and Pharmacy «Iuliu Hațieganu», Moților Street 33, Cluj-Napoca, Cluj, Romania 
Sponsor: Ivoclar Vivadent AG, Bendererstrasse 2, 9494 Schaa, Liechtenstein 
 
Revision History 
Version 
Date 
Author 
Remark on Amendments to the CIP 
1.0 
17.09.2021 
Dr. Ada Delean 
Initial creation 
2.0 
24.10.2023 
Dr. Ada Delean/Patrizia 
Elkuch-Hoch 
Formal Adjustments 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Clinical study of tooth enamel remineralization 
using an experimental remineralization product 
The Coordinating Investigator has approved the CIP version [2.0 (dated 24.10.2023), and 
confirm hereby to conduct the investigation according to the CIP, the current version of the 
World Medical Association Declaration of Helsinki, ISO14155 norm, ICH-GCP as far as 
applicable, and the local legally binding requirements. This includes in particular that the 
clinical investigation shall not begin until the required approval(s) have been obtained and that 
any additional requirements imposed by the EC or NCA shall be followed, if appropriate. 
 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Clinical study of tooth enamel remineralization 
using an experimental remineralization product 
Content 
1. 
SYNOPSIS 
4 
2. 
DEFINITIONS, TERMS, ABBREVIATIONS 
5 
3. 
STUDY SCHEDULE 
7 
4. 
STATISTICAL CONSIDERATIONS 
7 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Clinical study of tooth enamel remineralization 
using an experimental remineralization product 
1. Synopsis 
Sponsor/ 
Manufacturer 
Ivoclar Vivadent AG 
Bendererstrasse 2 
9494 Schaan 
Fürstentum Liechtenstein 
 
Study Title  
Clinical study of tooth enamel remineralization using an 
experimental remineralization product 
Short Title  
Clinical Evaluation of an Experimental Remineralization Product 
Version/ Date 
2.0/ 24.10.23 
Registration: 
 
 NCT06166849 (www.clinicaltrials.gov) 
Clinical 
investigation 
category and 
Rationale 
Medical Device Clinical Trial 
Background and 
Rationale: 
Dental caries develops when the homeostasis between phasic 
demineralization and remineralization of the tooth surface is out of 
balance. Topically applied fluoride delays demineralization and 
promotes remineralization. The Experimental Fluoride Product is a 
two-step fluoride-based remineralization system consisting of an 
aqueous fluoride solution (component A) and an ethanolic 
nanosolution of calcium fluoride (component B). After sequential 
application, the two components form a protective calcium-fluoride 
layer that is intended to promote remineralization of incipient 
enamel lesions and increase the acid resistance of dental tissue. 
The condition treated is incipient carious lesions or white spot 
lesions (WSL) on permanent teeth. Fluoride varnishes represent 
the current standard of care for non-invasive remineralization of 
early caries. Another more invasive treatment option is infiltration. 
Objective(s): 
Efficacy of an investigational medical device (Experimental Fluoride 
Product, Ivoclar-Vivadent AG, Schaan, Liechtenstein) compared to 
no treatment 
Outcome(s): 
The remineralizing effect of the product will be evaluated based on 
different outcome variables: 
• 
International Caries Detection and Assessment System 
(ICDAS) score 
• 
Lesion size 
• 
Surface texture (roughness) of the injured surface 
• 
Laser fluorescence 
• 
Visual assessment 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Clinical study of tooth enamel remineralization 
using an experimental remineralization product 
Clinical 
investigation 
design: 
Interventional split-mouth randomized -controlled clinical study 
Inclusion / 
Exclusion criteria: 
Female/male adult patients (age ≥ 18) consulting at the dental 
service department of UMF Iuliu Hațieganu, Cluj-Napoca, 
Romania. Inclusion criteria: At least two incipient carious lesions on 
the buccal or oral surface of permanent teeth; active carious 
lesions; patient at risk of caries; vital teeth. Exclusion criteria: 
Pregnancy; enamel removal at the investigation site; allergies 
against ingredients of the investigational device; chronic diseases. 
Intervention: 
Measurements and 
procedures 
At the initial session, the teeth will be professionally cleaned. 
Lesions will be isolated with cotton rolls and lingual suction and 
dried for ~5 seconds. Component A will be applied with a 
microbrush (60 s reaction time, removal of residual material). 
Component B will be applied with a new microbrush and will be 
allowed to dry for ≥ 30 s. Patients are instructed to not rinse, eat, or 
drink for 1 hour.  
Control Intervention 
(if applicable): 
No treatment will be done. 
Number of 
Participants with 
Rationale: 
It is aimed to include 40 subjects. Accordingly, the test and control 
group will involve ≥40 teeth. Exact numbers of teeth in both groups 
depend on the number of lesions presenting in subjects. 
Duration of the 
investigation: 
For each included patient, the study will run for one year.  
Investigation 
Schedule: 
Intervention, 1 day (optional), 4 weeks, 4 months, 12 months  
 
Study Coordinator: 
Dr. Radu Chisnoiu 
Principal 
Investigator: 
Dr. Ada Delean 
Investigation 
Site(s): 
Single-centre, Discipline of Odontology, Endodontics and Oral 
Pathology, University of Medicine and Pharmacy «Iuliu 
Hațieganu», Moților Street 33, Cluj-Napoca, Cluj, Romania 
Statistical 
Considerations: 
See Chapter 4. 
Compliance 
Statement: 
This clinical investigation will be conducted in compliance with the 
CIP (protocol), the current version of the Declaration of Helsinki, 
ISO EN 14155, ICH-GCP (as far as applicable) as well as all 
national legal and regulatory requirements.  
 
2. Definitions, Terms, Abbreviations 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Clinical study of tooth enamel remineralization 
using an experimental remineralization product 
ADE 
Adverse Device Effect. Adverse events (see below) that are 
related to the MD under investigation or the comparator and to 
the procedures involved.  
 
For users or other persons this is restricted to events related to 
the MD.  
AE 
 Adverse event (Art. 2 Abs 57 MDR): 
 
 Any untoward medical occurrence, unintended disease or injury 
or any untoward clinical signs (including an abnormal laboratory 
finding) in subjects, users or other persons whether or not related 
to the MD. 
Castor EDC 
Electronic data capturing (EDC) platform from the company 
Castor 
CE 
Conformité Européenne (Label on products complaint to 
European Medical Device Legislation) 
CER 
 
 
 
Clinical Evaluation Report 
CIP 
 
 
 
Clinical Investigation Plan 
CIR 
 
 
 
Clinical Investigation Report 
Clinical studies  
Systematic investigation in one or more human subjects, 
undertaken to assess the clinical performance, effectiveness or 
safety of a medical device. 
Note: For the purpose of this document, “clinical investigation” or “clinical trial” 
are synonymous with “clinical study” 
DD 
 
 
 
Device Deficiency (Art. 2 Abs 59 MDR): 
Inadequacy of a medical device related to its identity, quality, 
durability, reliability, safety or performance, of an investigational 
device, including malfunction, user errors and inadequate 
information supplied by the manufacturer. 
The definition includes deficiencies related to the investigational 
MD or the comparator MD.  
 
(e)CRF 
 
 
(electronic) Case Report Form 
ICH-GCP 
International Conference on Harmonisation – Good Clinical 
Practice 
IB 
Investigator's Brochure 
ICF 
Informed Consent Form 
ISO 
International Organization for Standardization 
MD 
 
 
 
Medical Device 
Directive) 
PI 
Principal Investigator 
SAE 
Serious adverse event: (Art. 2 Abs 58 MDR) 
 
Any adverse event (see definition above) that led to any of the 
following: 
(a) death,  
(b) serious deterioration in the health of the subject that resulted 
in any of the following:  
(i) life-threatening illness or injury, 
(ii) permanent impairment of a body structure or a body function, 
(iii) hospitalization or prolongation of patient hospitalization*, 
(iv) medical or surgical intervention to prevent life-threatening 
illness or injury or permanent impairment to a body structure or a 
body function, 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Clinical study of tooth enamel remineralization 
using an experimental remineralization product 
(v) chronic disease, 
(c) foetal distress, foetal death or a congenital physical or mental 
impairment or birth defect. 
*Note: planned hospitalization for pre-existing condition, or a 
procedure required by the CIP, without a serious deterioration of 
the health status of the subject, is not considered an SAE 
SADE   
 
 
Suspected Serious Device Effect.  
Subjects                                 SAE related to the MD and/or the comparator 
 
Participants (i.e. Patients) that are included in a clinical 
investigation. 
3. Study Schedule 
 
4. Statistical Considerations 
Statistical methods are limited to descriptive statistics and to simple parametric or non-
parametric tests (depending on data distribution).