Condition category
Oral Health
Date applied
29/06/2018
Date assigned
20/07/2018
Last edited
16/07/2018
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Background and study aims
Dental caries is a disease caused by bacteria that leads to cavity formation in the teeth. These cavities can eventually cause loss of teeth. In children, caries is a more aggressive disease and is a public health issue in many countries, because the cavities that form are difficult to treat and control at such a young age, often causing infections that may affect the child’s growth and development. We still have not identified an easy and cost-effective way to prevent cavities in children. This study aims to test the use of two different substances, thymol (THY) and carvacrol (CAR), against dental caries in children, comparing the effect of these substances with chlorhexidine (CHX) and fluoride.

Who can participate in the study?
120 healthy children of both sexes, aged 31-60 months, enrolled to participate in this study.

What does the study involve?
The study involved application of a varnish (transparent or colored liquid that adheres to the teeth) to the child’s teeth. These varnishes contained one of these substances: CAR, CAR and THY, CHX or Fluoride. Children were treated with one of these varnishes and followed-up during 12 months to see if these substances could prevent cavities, and which substance was better at preventing cavities. Not all participants received the same treatment, so a lottery system was used to decide which treatment to use for each participant. When a child started out the study being treated with one substance (decision made through the lottery system), they would join a specific “treatment group”, and were only treated with this substance until the end of the study. Varnishes were applied, examinations were performed and bacteria was measured in saliva before treatment, and 7, 30, 90, 180 and 360 days after initial treatment. A single dentist examined all children. To collect saliva, children were asked to chew on a piece of paraffin and spit in a cup. The saliva was then diluted and cultured to evaluate growth of Streptococcus mutans (the main bacterium that causes caries).

What are the possible benefits and risks of participating?
These children benefited by being closely followed for dental caries at no cost, and they all received free dental brushes and toothpastes. There were no risks involved in the study. Some children experienced a burning sensation right after treatment application (similar to what is felt after brushing with adult toothpaste).

Where is the study run from?
The study was run from the public school (kindergarten and daycare) at the “Executiva Regional SER IV” in Fortaleza (Brazil), and at the Pediatric Dental Clinic of the Federal University of Ceará.

When is the study starting and how long is it expected to run for?
May 2008 to February 2010.

Who is funding the study?
The study was partly funded by the Brazilian government through the National Council for Scientific and Technological Development (CNPq).

Who is the main contact?
1. Dr. Cristiane Fonteles. Federal University of Ceará. Postgraduate Program in Dentistry. Phone/Fax:+55-85-33668232, E-mail: cfontele@ufc.br
2. Dr. Jorgeana Abrahão Barroso. Phone: +55-85-33668408, E-mail: jorgeana_abrahao@hotmail.com

Trial website

Contact information

Type

Scientific

Primary contact

Prof Cristiane Sá Roriz Fonteles

ORCID ID

http://orcid.org/0000-0003-4197-6002

Contact details

Department of Clinical Dentistry
Postgraduate Program in Dentistry
Rua Monsenhor Furtado
1273
Fortaleza
60430-355
Brazil

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

136/08

Study information

Scientific title

In vivo activity of Carvacrol and Thymol in the inhibition of mutans streptococci and caries experience in high-risk caries-free children: a longitudinal study

Acronym

Study hypothesis

Carvacrol and Thymol do not differ in their antimicrobial activity against mutans streptococci and their anticaries properties , when compared to Chlorhexidine and Sodium Fluoride.

Ethics approval

Ethics Committee in Research of the Federal University of Ceará (Brazil) - COMEPE, 25/09/2008, 136/08

Study design

Randomized parallel double-blind clinical trial

Primary study design

Interventional

Secondary study design

Randomised parallel trial

Trial setting

Schools

Trial type

Prevention

Patient information sheet

Not available in web format, please use contact details to request a participant information sheet.

Condition

Early childhood caries

Intervention

120 children were randomly divided into 4 groups based on the application of different formulations: group 1 (20% carvacrol), group 2 (10% carvacrol + 10% thymol), group 3 (20% chlorhexidine) and group 4 (5% sodium fluoride). The varnishes were similar in color, odor, texture and flavor. The manipulation of them was performed in the laboratory of Clinical Analysis, Faculty of Pharmacy, Dentistry and Nursing, Federal University of Ceará, Brazil. Then they were stored in an aluminum tube and identified by alphabet letters. The 5% sodium fluoride was purchased ready to use (Duraphat®/Colgate). The varnish application was performed in a standardized way, with microbrush® once every 3 months during a period of 1 year. Patients were monitored for the appearance of dental caries cavitated or non-cavitated lesions, during the 12 months of treatment, with clinical examinations every 3 months.

Intervention type

Other

Phase

Drug names

Primary outcome measure

Dental caries assessed by dental examinations performed by a single examiner during a 12-month period. These examinations were carried out before beginning of treatment, and 7, 30, 90, 180 and 360 days after initiation of treatment. In order to minimize the diagnostic bias between groups, a calibration of the examiner was performed, according to criteria recommended by the World Health Organization (1993). A mean Kappa of 0.83 was obtained, that is considered a good or excellent intra-examiner agreement level (Eklund, Moller, Leclerq, 1996).

Secondary outcome measures

Levels of mutans streptococci in saliva. Upon completion of the initial dental examination, a saliva sample was collected from each participant for the first microbiological analysis (baseline (B), before the start of treatment and 5 collections, 7 (D7), 30 (D30), 90 (D90), 180 (D180) and 360 (D360) days after the start of treatment. One hour prior to saliva collection children performed oral hygiene. Stimulated saliva collection was performed by asking the child to chew a piece of paraffin (3x3cm) Parafilm “M”® Laboratory Film (American National Can, Greenwich, CT) for 60 s. Then saliva was collected in the first minute, transferred into sterile tubes Eppendorfs® and transported for further analysis. The medium used for MS culture was mitis salivarius bacitracin agar (MSB) (Difco, Detroit, Michigan, USA) supplemented with 1% potassium tellurite (Vetec Fine chemicals LTDA, Rio de Janeiro), 1% bacitracin (Sigma) and 15% sucrose (Merck) (Gold, Jordan, Van Houte, 1973).
For microbiological analysis, saliva was diluted into 1:10 and 1:100 dilutions to allow the counting of MS. A volume of 20 μL of each dilution or pure saliva was cultured in triplicate in MSB agar, being spread using a tip in a Petri plate, that were then incubated in a bacteriological incubator (Biomatic) at 37°C in a microaerophilic environment for 48 h. After this period, MS colonies were counted (Western, Krass, 1978) through visual observation (Koneman, 2001) and converted into CFU/ml of saliva.

Overall trial start date

05/05/2008

Overall trial end date

01/02/2010

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

1. Aged 36–71 months
2. Caries-free children without past caries
3. At a high-risk category for dental caries according to the 2010 guidelines of the American Academy of Pediatric Dentistry
4. Enrolled in schools and preschools in the city of Fortaleza (Brazil)

Participant type

Healthy volunteer

Age group

Child

Gender

Both

Target number of participants

A total of 120 children were included in the study. These children were randomly divided into 4 treatment groups (n=30 each).

Participant exclusion criteria

1. History of allergic diseases (asthma, rhinitis, sinusitis, skin rash)
2. History of allergies to medications and food
3. Aphthous ulcers or lesions affecting the oral mucosa
4. Taking antibiotics during the study period
5. Parents or legal guardians refused to sign the informed consent

Recruitment start date

01/11/2008

Recruitment end date

01/02/2009

Locations

Countries of recruitment

Brazil

Trial participating centre

Federal University of Ceará
Rua Monsenhor Furtado, 1273 Rodolfo Teófilo
Fortaleza
60430-355
Brazil

Trial participating centre

Executiva Regional SER IV
Avenida Dede Brasil, 3770 - Serrinha.
Fortaleza
60346-196
Brazil

Sponsor information

Organisation

Federal University of Ceará - Comitê de Ética em Pesquisa - UFC/PROPESQ

Sponsor details

Rua Coronel Nunes de Melo
1000 - Rodolfo Teófilo
Fortaleza
60416-000
Brazil

Sponsor type

Research council

Website

http://www.dvprppg.ufc.br/cep/index.php/pt-br/contato

Funders

Funder type

Not defined

Funder name

Conselho Nacional de Desenvolvimento Científico e Tecnológico

Alternative name(s)

National Council for Scientific and Technological Development, CNPq

Funding Body Type

government organisation

Funding Body Subtype

National government

Location

Brazil

Results and Publications

Publication and dissemination plan

The results of this trial are being submitted as a single publication to the Journal of Caries Research.

IPD sharing statement:
The datasets generated and/or analysed during the current study will be included in the subsequent results publication. This dataset consists of statistics of the following variables: age/sex of participants, timing of data collection, mutans streptococci levels in saliva and number of decayed, missing and filled surfaces (dmfs) obtained throughout the study evaluation period. We do not have consent from participants to provide access to patient’s raw data.

Intention to publish date

06/08/2018

Participant level data

Available on request

Basic results (scientific)

We observed an increase in MS in the groups treated with CHX and NaF at D360. There was a significant difference between the caries densities in each group (p=0,001). Comparison between caries density in relation to age within each group and between groups did not show a statistical difference. Caries increments did not differ within or between groups. In conclusion, all treatments produced significant reduction of EGM, associated with low caries experience and the results suggest that all the substances tested reduced the appearance of new caries lesions.

Publication list

Publication citations

Additional files

Editorial Notes