<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT04460755</url>
  </required_header>
  <id_info>
    <org_study_id>05-PA-30-9/2018.</org_study_id>
    <secondary_id>2181-198-03-04-17-0063</secondary_id>
    <nct_id>NCT04460755</nct_id>
  </id_info>
  <brief_title>Tooth Whitening Evaluation With Cytotoxic and Genotoxic Effect of Commercial Whitening Toothpastes on Oral Mucosal Cells</brief_title>
  <official_title>Tooth Whitening Evaluation With Cytotoxic and Genotoxic Effect of Commercial Whitening Toothpastes on Oral Mucosal Cells</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Zagreb</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Zagreb</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Bleaching discolored vital teeth is one of the most popular aesthetic treatment in dentistry&#xD;
      in the last decade. Teeth whitening can be performed by professionals/dentists in the dental&#xD;
      office (&quot;in-office&quot;) and by the patients themselves at home (over-the-counter). A generally&#xD;
      available method for teeth whitening is to use toothpastes which contain whitening&#xD;
      ingredients. This method presents commercial option to remove discolorations on the enamel&#xD;
      surface of vital teeth. There are many commercially available dentifrices that contain&#xD;
      whitening agents, such as abrasives, chemical or optical agents. It has been noticed that&#xD;
      whitening agents added in toothpastes can provide whitening effect visible to human eye that&#xD;
      can objectively be evaluated by using sprectrophotometers. The results of teeth whitening can&#xD;
      also be obtained subjectively by observation and comparison to tooth shade guide. Also, these&#xD;
      products must be used with caution as they may cause some negative effects, such as dentinal&#xD;
      hypersensitivity, irritations, peeling/exfoliation, dry mouth, rougher teeth and cytotoxic&#xD;
      and genotoxic effect on oral mucosa cells. Studies that have already been conducted with&#xD;
      whitening agents are based on abrasives, peroxides, optical agents and activated charcoal.&#xD;
&#xD;
      The main objective in this study is to investigate the effectiveness of different brands of&#xD;
      toothpastes with whitening effect and their performance (effect) on oral mucosa cells. As a&#xD;
      measure of genotoxicity and cytotoxicity in cells, the number of micronuclei and other&#xD;
      morphological changes of the nucleus are determined (micronucleus assay). Other specific&#xD;
      objectives are to investigate the patient satisfaction with the characteristic of treatment&#xD;
      such as final tooth color, color stability, length of treatment, comfort during treatment and&#xD;
      overall participant satisfaction.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Sample description and study design for this research was performed at the School of the&#xD;
      Medicine, University of Split, Croatia.&#xD;
&#xD;
      Respondents are the students and employees of the School of the Medicine University of Split,&#xD;
      Croatia. They will be divided in groups where different types of whitening toothpaste will be&#xD;
      used. One group will use control non-whitening toothpaste. All respondents will use the same&#xD;
      toothbrush during the research. Before using whitening toothpastes, all participants will use&#xD;
      the same non-whitening toothpaste for one month. All participants will sign informed consent&#xD;
      for participation in the research. Their participation will be voluntary. Respondents will be&#xD;
      able to refuse to participate in the research without any consequences.&#xD;
&#xD;
      This study is approved by Ethic Committee of the School of Dental Medicine, Zagreb, Croatia&#xD;
      (09.2018.) and Ethic Committee of the School of the Medicine University of Split, Croatia&#xD;
      (12.2017). The study is randomized, prospective clinical trial.&#xD;
&#xD;
      The participants will be randomly selected for the whitening toothpaste groups and for the&#xD;
      control non-whitening group. A sample of cells from the buccal mucosa area will be taken from&#xD;
      each patient prior using the toothpastes under test, 30 and 60 days after the beginning and&#xD;
      30 days after using the toothpastes under test. Color assessment will be performed four times&#xD;
      using the Vita Easyshade digital spectrophotometer: T0- before treatment (initial); T1- 30&#xD;
      days after the beginning; T2- 60 days after the beginning and T3- 90 days after the beginning&#xD;
      of the study (i.e. 30 days after completing the treatment). The color reading will be&#xD;
      performed in the middle third of the labial surface of the tooth, in the same environment and&#xD;
      with the same light conditions. The measurement will be performed on all vital six anterior&#xD;
      maxillary teeth, free of caries and restorations. Participant's satisfaction with the&#xD;
      treatment and the toothpaste used will be assessed using the prepared questionnaires.&#xD;
&#xD;
      Participants will use toothpastes under test for two months. Toothpaste will be applied twice&#xD;
      a day, in the morning and in the evening, for three minutes for 1g (app. 2 cm). During the&#xD;
      experiment, the examinees will not use any toothpaste other than the one under test.&#xD;
      Participants will use no other agents for oral hygiene.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date type="Actual">January 1, 2019</start_date>
  <completion_date type="Anticipated">September 30, 2020</completion_date>
  <primary_completion_date type="Anticipated">July 31, 2020</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>The study is randomized, prospective clinical trial.</intervention_model_description>
    <primary_purpose>Screening</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Color assessment before the treatment (T0)</measure>
    <time_frame>0 days</time_frame>
    <description>The following measurements were will be recorded: L*,a*, b* values for all teeth as well as the tooth shade. The color was will be established by CIELAB color space. ΔE is will be calculated using the following formula: ΔE=√(〖(ΔL*)〗^2+〖(Δa*)〗^2+〖(Δb*)〗^2 ). The color changes between the evaluation times in each tested group and between groups were will be analysed using the ΔE, ΔL*, Δa* and Δb*values. To calculate the difference in tooth shade according to the Vita Classical scale, the recorded values were will be ordered in scores from 1 to 16 in a luminosity sequence.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Color change after 30 days of treatment (T1)</measure>
    <time_frame>30 days</time_frame>
    <description>The following measurements were will be recorded: L*,a*, b* values for all teeth as well as the tooth shade. The color was will be established by CIELAB color space. ΔE is will be calculated using the following formula: ΔE=√(〖(ΔL*)〗^2+〖(Δa*)〗^2+〖(Δb*)〗^2 ). The color changes between the evaluation times in each tested group and between groups were will be analysed using the ΔE, ΔL*, Δa* and Δb*values. To calculate the difference in tooth shade according to the Vita Classical scale, the recorded values were will be ordered in scores from 1 to 16 in a luminosity sequence.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Color change after 60 days of treatment (T2)</measure>
    <time_frame>60 days</time_frame>
    <description>The following measurements were will be recorded: L*,a*, b* values for all teeth as well as the tooth shade. The color was will be established by CIELAB color space. ΔE is will be calculated using the following formula: ΔE=√(〖(ΔL*)〗^2+〖(Δa*)〗^2+〖(Δb*)〗^2 ). The color changes between the evaluation times in each tested group and between groups were will be analysed using the ΔE, ΔL*, Δa* and Δb*values. To calculate the difference in tooth shade according to the Vita Classical scale, the recorded values were will be ordered in scores from 1 to 16 in a luminosity sequence.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Color change 30 days after the treatment (90 days from the beginning of treatment) (T3)</measure>
    <time_frame>90 days</time_frame>
    <description>The following measurements were will be recorded: L*,a*, b* values for all teeth as well as the tooth shade. The color was will be established by CIELAB color space. ΔE is will be calculated using the following formula: ΔE=√(〖(ΔL*)〗^2+〖(Δa*)〗^2+〖(Δb*)〗^2 ). The color changes between the evaluation times in each tested group and between groups were will be analysed using the ΔE, ΔL*, Δa* and Δb*values. To calculate the difference in tooth shade according to the Vita Classical scale, the recorded values were will be ordered in scores from 1 to 16 in a luminosity sequence.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Assessment of biocompatibility before the treatment (T0)</measure>
    <time_frame>0 days</time_frame>
    <description>Assessment of biocompatibility through cytotoxicity and genotoxicity parameters of commercially available toothpastes with whitening effect will be performed using micronucleus assay.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Assessment of biocompatibility after 30 days of treatment (T1)</measure>
    <time_frame>30 days</time_frame>
    <description>Assessment of biocompatibility through cytotoxicity and genotoxicity parameters of commercially available toothpastes with whitening effect will be performed using micronucleus assay.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Assessment of biocompatibility after 60 days of treatment (T2)</measure>
    <time_frame>60 days</time_frame>
    <description>Assessment of biocompatibility through cytotoxicity and genotoxicity parameters of commercially available toothpastes with whitening effect will be performed using micronucleus assay.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Assessment of biocompatibility 30 days after the treatment (90 days from the beginning of treatment) (T3)</measure>
    <time_frame>90 days</time_frame>
    <description>Assessment of biocompatibility through cytotoxicity and genotoxicity parameters of commercially available toothpastes with whitening effect will be performed using micronucleus assay.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Assessment of participant's satisfaction with treatment and used toothpaste after 60 days of treatment</measure>
    <time_frame>60 days</time_frame>
    <description>Assessment of participant's satisfaction with treatment and used toothpaste will be performed by prepared questionnaire for the study. Respondents will complete a questionnaire of eating and living habits, too</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assessment of participant's satisfaction with treatment of used toothpaste 30 days after the treatment (90 days from the beginning of treatment)</measure>
    <time_frame>90 days</time_frame>
    <description>Assessment of participant's satisfaction with treatment and used toothpaste will be performed by prepared questionnaire for the study.</description>
  </secondary_outcome>
  <number_of_arms>6</number_of_arms>
  <enrollment type="Anticipated">210</enrollment>
  <condition>Teeth Whitening</condition>
  <arm_group>
    <arm_group_label>Control group</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>A group of participants that will be using toothpaste without tooth whitening ingredients.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Whitening toothpaste 1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>A group of participants that will be using urea peroxide whitening toothpastes.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Whitening toothpaste 2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>A group of participants that will be using hydrogen peroxide whitening toothpastes.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Whitening toothpaste 3</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>A group of participants that will be using whitening toothpastes that contain abrasive ingredients.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Whitening toothpaste 4</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>A group of participants that will be using whitening toothpastes that contain enzymes as whitening ingredients.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Whitening toothpaste 5</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>A group of participants that will be using toothpastes that contain an activated charcoal.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Control group</intervention_name>
    <description>A sample of cells from the buccal mucosa area will be taken with cytological sampling brush and will be fixed on on a microscopy slide and stained with a Feulgen fast green solution. The samples will be analyzed by electron microscopy. Tooth color will be measured, verified and evaluated with a Vita Easyshade V digital spectrophotometer in initial phase, after one month of usage, after two months of usage and one month after the end of usage.&#xD;
Before using any of the whitening toothpaste under test, every participant will use non whitening toothpaste for one month, twice a day.&#xD;
Satisfaction and impression with treatment will be recorded with the questionnaires provided for this study.</description>
    <arm_group_label>Control group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Whitening toothpaste 1</intervention_name>
    <description>A sample of cells from the buccal mucosa area will be taken with cytological sampling brush and will be fixed on on a microscopy slide and stained with a Feulgen fast green solution. The samples will be analyzed by electron microscopy. Tooth color will be measured, verified and evaluated with a Vita Easyshade V digital spectrophotometer in initial phase, after one month of usage, after two months of usage and one month after the end of usage.&#xD;
Before using any of the whitening toothpaste under test, every participant will use non whitening toothpaste for one month, twice a day.&#xD;
Satisfaction and impression with treatment will be recorded with the questionnaires provided for this study.</description>
    <arm_group_label>Whitening toothpaste 1</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Whitening toothpaste 2</intervention_name>
    <description>A sample of cells from the buccal mucosa area will be taken with cytological sampling brush and will be fixed on on a microscopy slide and stained with a Feulgen fast green solution. The samples will be analyzed by electron microscopy. Tooth color will be measured, verified and evaluated with a Vita Easyshade V digital spectrophotometer in initial phase, after one month of usage, after two months of usage and one month after the end of usage.&#xD;
Before using any of the whitening toothpaste under test, every participant will use non whitening toothpaste for one month, twice a day.&#xD;
Satisfaction and impression with treatment will be recorded with the questionnaires provided for this study.</description>
    <arm_group_label>Whitening toothpaste 2</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Whitening toothpaste 3</intervention_name>
    <description>A sample of cells from the buccal mucosa area will be taken with cytological sampling brush and will be fixed on on a microscopy slide and stained with a Feulgen fast green solution. The samples will be analyzed by electron microscopy. Tooth color will be measured, verified and evaluated with a Vita Easyshade V digital spectrophotometer in initial phase, after one month of usage, after two months of usage and one month after the end of usage.&#xD;
Before using any of the whitening toothpaste under test, every participant will use non whitening toothpaste for one month, twice a day.&#xD;
Satisfaction and impression with treatment will be recorded with the questionnaires provided for this study.</description>
    <arm_group_label>Whitening toothpaste 3</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Whitening toothpaste 4</intervention_name>
    <description>A sample of cells from the buccal mucosa area will be taken with cytological sampling brush and will be fixed on on a microscopy slide and stained with a Feulgen fast green solution. The samples will be analyzed by electron microscopy. Tooth color will be measured, verified and evaluated with a Vita Easyshade V digital spectrophotometer in initial phase, after one month of usage, after two months of usage and one month after the end of usage.&#xD;
Before using any of the whitening toothpaste under test, every participant will use non whitening toothpaste for one month, twice a day.&#xD;
Satisfaction and impression with treatment will be recorded with the questionnaires provided for this study.</description>
    <arm_group_label>Whitening toothpaste 4</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Whitening toothpaste 5</intervention_name>
    <description>A sample of cells from the buccal mucosa area will be taken with cytological sampling brush and will be fixed on on a microscopy slide and stained with a Feulgen fast green solution. The samples will be analyzed by electron microscopy. Tooth color will be measured, verified and evaluated with a Vita Easyshade V digital spectrophotometer in initial phase, after one month of usage, after two months of usage and one month after the end of usage.&#xD;
Before using any of the whitening toothpaste under test, every participant will use non whitening toothpaste for one month, twice a day.&#xD;
Satisfaction and impression with treatment will be recorded with the questionnaires provided for this study.</description>
    <arm_group_label>Whitening toothpaste 5</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  age of 18 and older&#xD;
&#xD;
          -  non smokers&#xD;
&#xD;
          -  good oral and general health&#xD;
&#xD;
          -  excellent oral hygiene&#xD;
&#xD;
          -  vital six anterior maxillary teeth free of caries or restorations&#xD;
&#xD;
          -  tooth shade A2 or darker&#xD;
&#xD;
          -  no cervical lesions or prosthodontic treatments&#xD;
&#xD;
          -  no periodontal disease&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  pregnant women&#xD;
&#xD;
          -  breastfeeding women&#xD;
&#xD;
          -  individuals with discolored teeth (tetracycline stain, fluorosis)&#xD;
&#xD;
          -  tooth sensitivity&#xD;
&#xD;
          -  history of allergy to any dental hygiene product&#xD;
&#xD;
          -  individuals who had previously undergone any tooth whitening treatment&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>School of the Medicine, University of Split</name>
      <address>
        <city>Split</city>
        <zip>21000</zip>
        <country>Croatia</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Croatia</country>
  </location_countries>
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    <citation>Holland N, Bolognesi C, Kirsch-Volders M, Bonassi S, Zeiger E, Knasmueller S, Fenech M. The micronucleus assay in human buccal cells as a tool for biomonitoring DNA damage: the HUMN project perspective on current status and knowledge gaps. Mutat Res. 2008 Jul-Aug;659(1-2):93-108. doi: 10.1016/j.mrrev.2008.03.007. Epub 2008 Apr 11.</citation>
    <PMID>18514568</PMID>
  </reference>
  <reference>
    <citation>Thomas P, Fenech M. Buccal micronucleus cytome assay. Methods Mol Biol. 2011;682:235-48. doi: 10.1007/978-1-60327-409-8_17.</citation>
    <PMID>21057932</PMID>
  </reference>
  <reference>
    <citation>Torres-Bugarin O, Zavala-Cerna MG, Nava A, Flores-Garcia A, Ramos-Ibarra ML. Potential uses, limitations, and basic procedures of micronuclei and nuclear abnormalities in buccal cells. Dis Markers. 2014;2014:956835. doi: 10.1155/2014/956835. Epub 2014 Feb 4.</citation>
    <PMID>24778463</PMID>
  </reference>
  <reference>
    <citation>Bolognesi C, Knasmueller S, Nersesyan A, Thomas P, Fenech M. The HUMNxl scoring criteria for different cell types and nuclear anomalies in the buccal micronucleus cytome assay - an update and expanded photogallery. Mutat Res. 2013 Oct-Dec;753(2):100-113. doi: 10.1016/j.mrrev.2013.07.002. Epub 2013 Aug 11.</citation>
    <PMID>23942275</PMID>
  </reference>
  <reference>
    <citation>Tolbert PE, Shy CM, Allen JW. Micronuclei and other nuclear anomalies in buccal smears: methods development. Mutat Res. 1992 Feb;271(1):69-77. doi: 10.1016/0165-1161(92)90033-i.</citation>
    <PMID>1371831</PMID>
  </reference>
  <reference>
    <citation>Tadin A, Gavic L, Zeravica A, Ugrin K, Galic N, Zeljezic D. Assessment of cytotoxic and genotoxic effects of conventional and whitening kinds of toothpaste on oral mucosa cells. Acta Odontol Scand. 2018 Jan;76(1):64-70. doi: 10.1080/00016357.2017.1384567. Epub 2017 Sep 29.</citation>
    <PMID>28959909</PMID>
  </reference>
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    <citation>Tadin A, Gavic L, Govic T, Galic N, Zorica Vladislavic N, Zeljezic D. In vivo evaluation of fluoride and sodium lauryl sulphate in toothpaste on buccal epithelial cells toxicity. Acta Odontol Scand. 2019 Jul;77(5):386-393. doi: 10.1080/00016357.2019.1577988. Epub 2019 Feb 20. Erratum In: Acta Odontol Scand. 2019 Aug;77(6):483.</citation>
    <PMID>30784350</PMID>
  </reference>
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    <citation>Tadin A, Galic N, Mladinic M, Marovic D, Kovacic I, Zeljezic D. Genotoxicity in gingival cells of patients undergoing tooth restoration with two different dental composite materials. Clin Oral Investig. 2014 Jan;18(1):87-96. doi: 10.1007/s00784-013-0933-3. Epub 2013 Feb 5.</citation>
    <PMID>23385426</PMID>
  </reference>
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    <citation>Akarslan ZZ, Sadik B, Erten H, Karabulut E. Dental esthetic satisfaction, received and desired dental treatments for improvement of esthetics. Indian J Dent Res. 2009 Apr-Jun;20(2):195-200. doi: 10.4103/0970-9290.52902.</citation>
    <PMID>19553722</PMID>
  </reference>
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    <citation>Sabherwal RS, Gonzalez J, Naini FB. Assessing the influence of skin color and tooth shade value on perceived smile attractiveness. J Am Dent Assoc. 2009 Jun;140(6):696-705. doi: 10.14219/jada.archive.2009.0256.</citation>
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    <citation>Kershaw S, Newton JT, Williams DM. The influence of tooth colour on the perceptions of personal characteristics among female dental patients: comparisons of unmodified, decayed and 'whitened' teeth. Br Dent J. 2008 Mar 8;204(5):E9; discussion 256-7. doi: 10.1038/bdj.2008.134. Epub 2008 Feb 15.</citation>
    <PMID>18297050</PMID>
  </reference>
  <reference>
    <citation>Angel P, Bersezio C, Estay J, Werner A, Retamal H, Araya C, Martin J, Fernandez E. Color stability, psychosocial impact, and effect on self-perception of esthetics of tooth whitening using low-concentration (6%) hydrogen peroxide. Quintessence Int. 2018;49(7):557-566. doi: 10.3290/j.qi.a40468.</citation>
    <PMID>29786702</PMID>
  </reference>
  <verification_date>July 2020</verification_date>
  <study_first_submitted>June 27, 2020</study_first_submitted>
  <study_first_submitted_qc>July 2, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 8, 2020</study_first_posted>
  <last_update_submitted>July 2, 2020</last_update_submitted>
  <last_update_submitted_qc>July 2, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">July 8, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Zagreb</investigator_affiliation>
    <investigator_full_name>Nada Zorica Vladislavic</investigator_full_name>
    <investigator_title>Tooth Whitening Evaluation With Cytotoxic and Genotoxic Effect of Commercial Whitening Toothpastes on Oral Mucosal Cells</investigator_title>
  </responsible_party>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04460755
org study id: 05-PA-30-9/2018.
secondary id: 2181-198-03-04-17-0063
nct id: NCT04460755
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Bleaching discolored vital teeth is one of the most popular aesthetic treatment in dentistry
      in the last decade. Teeth whitening can be performed by professionals/dentists in the dental
      office ("in-office") and by the patients themselves at home (over-the-counter). A generally
      available method for teeth whitening is to use toothpastes which contain whitening
      ingredients. This method presents commercial option to remove discolorations on the enamel
      surface of vital teeth. There are many commercially available dentifrices that contain
      whitening agents, such as abrasives, chemical or optical agents. It has been noticed that
      whitening agents added in toothpastes can provide whitening effect visible to human eye that
      can objectively be evaluated by using sprectrophotometers. The results of teeth whitening can
      also be obtained subjectively by observation and comparison to tooth shade guide. Also, these
      products must be used with caution as they may cause some negative effects, such as dentinal
      hypersensitivity, irritations, peeling/exfoliation, dry mouth, rougher teeth and cytotoxic
      and genotoxic effect on oral mucosa cells. Studies that have already been conducted with
      whitening agents are based on abrasives, peroxides, optical agents and activated charcoal.

      The main objective in this study is to investigate the effectiveness of different brands of
      toothpastes with whitening effect and their performance (effect) on oral mucosa cells. As a
      measure of genotoxicity and cytotoxicity in cells, the number of micronuclei and other
      morphological changes of the nucleus are determined (micronucleus assay). Other specific
      objectives are to investigate the patient satisfaction with the characteristic of treatment
      such as final tooth color, color stability, length of treatment, comfort during treatment and
      overall participant satisfaction.
Sample description and study design for this research was performed at the School of the
      Medicine, University of Split, Croatia.

      Respondents are the students and employees of the School of the Medicine University of Split,
      Croatia. They will be divided in groups where different types of whitening toothpaste will be
      used. One group will use control non-whitening toothpaste. All respondents will use the same
      toothbrush during the research. Before using whitening toothpastes, all participants will use
      the same non-whitening toothpaste for one month. All participants will sign informed consent
      for participation in the research. Their participation will be voluntary. Respondents will be
      able to refuse to participate in the research without any consequences.

      This study is approved by Ethic Committee of the School of Dental Medicine, Zagreb, Croatia
      (09.2018.) and Ethic Committee of the School of the Medicine University of Split, Croatia
      (12.2017). The study is randomized, prospective clinical trial.

      The participants will be randomly selected for the whitening toothpaste groups and for the
      control non-whitening group. A sample of cells from the buccal mucosa area will be taken from
      each patient prior using the toothpastes under test, 30 and 60 days after the beginning and
      30 days after using the toothpastes under test. Color assessment will be performed four times
      using the Vita Easyshade digital spectrophotometer: T0- before treatment (initial); T1- 30
      days after the beginning; T2- 60 days after the beginning and T3- 90 days after the beginning
      of the study (i.e. 30 days after completing the treatment). The color reading will be
      performed in the middle third of the labial surface of the tooth, in the same environment and
      with the same light conditions. The measurement will be performed on all vital six anterior
      maxillary teeth, free of caries and restorations. Participant's satisfaction with the
      treatment and the toothpaste used will be assessed using the prepared questionnaires.

      Participants will use toothpastes under test for two months. Toothpaste will be applied twice
      a day, in the morning and in the evening, for three minutes for 1g (app. 2 cm). During the
      experiment, the examinees will not use any toothpaste other than the one under test.
      Participants will use no other agents for oral hygiene.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: The study is randomized, prospective clinical trial.
primary purpose: Screening
masking: None (Open Label)
measure: Color assessment before the treatment (T0)
time frame: 0 days
description: The following measurements were will be recorded: L*,a*, b* values for all teeth as well as the tooth shade. The color was will be established by CIELAB color space. ΔE is will be calculated using the following formula: ΔE=√(〖(ΔL*)〗^2+〖(Δa*)〗^2+〖(Δb*)〗^2 ). The color changes between the evaluation times in each tested group and between groups were will be analysed using the ΔE, ΔL*, Δa* and Δb*values. To calculate the difference in tooth shade according to the Vita Classical scale, the recorded values were will be ordered in scores from 1 to 16 in a luminosity sequence.
measure: Color change after 30 days of treatment (T1)
time frame: 30 days
description: The following measurements were will be recorded: L*,a*, b* values for all teeth as well as the tooth shade. The color was will be established by CIELAB color space. ΔE is will be calculated using the following formula: ΔE=√(〖(ΔL*)〗^2+〖(Δa*)〗^2+〖(Δb*)〗^2 ). The color changes between the evaluation times in each tested group and between groups were will be analysed using the ΔE, ΔL*, Δa* and Δb*values. To calculate the difference in tooth shade according to the Vita Classical scale, the recorded values were will be ordered in scores from 1 to 16 in a luminosity sequence.
measure: Color change after 60 days of treatment (T2)
time frame: 60 days
description: The following measurements were will be recorded: L*,a*, b* values for all teeth as well as the tooth shade. The color was will be established by CIELAB color space. ΔE is will be calculated using the following formula: ΔE=√(〖(ΔL*)〗^2+〖(Δa*)〗^2+〖(Δb*)〗^2 ). The color changes between the evaluation times in each tested group and between groups were will be analysed using the ΔE, ΔL*, Δa* and Δb*values. To calculate the difference in tooth shade according to the Vita Classical scale, the recorded values were will be ordered in scores from 1 to 16 in a luminosity sequence.
measure: Color change 30 days after the treatment (90 days from the beginning of treatment) (T3)
time frame: 90 days
description: The following measurements were will be recorded: L*,a*, b* values for all teeth as well as the tooth shade. The color was will be established by CIELAB color space. ΔE is will be calculated using the following formula: ΔE=√(〖(ΔL*)〗^2+〖(Δa*)〗^2+〖(Δb*)〗^2 ). The color changes between the evaluation times in each tested group and between groups were will be analysed using the ΔE, ΔL*, Δa* and Δb*values. To calculate the difference in tooth shade according to the Vita Classical scale, the recorded values were will be ordered in scores from 1 to 16 in a luminosity sequence.
measure: Assessment of biocompatibility before the treatment (T0)
time frame: 0 days
description: Assessment of biocompatibility through cytotoxicity and genotoxicity parameters of commercially available toothpastes with whitening effect will be performed using micronucleus assay.
measure: Assessment of biocompatibility after 30 days of treatment (T1)
time frame: 30 days
description: Assessment of biocompatibility through cytotoxicity and genotoxicity parameters of commercially available toothpastes with whitening effect will be performed using micronucleus assay.
measure: Assessment of biocompatibility after 60 days of treatment (T2)
time frame: 60 days
description: Assessment of biocompatibility through cytotoxicity and genotoxicity parameters of commercially available toothpastes with whitening effect will be performed using micronucleus assay.
measure: Assessment of biocompatibility 30 days after the treatment (90 days from the beginning of treatment) (T3)
time frame: 90 days
description: Assessment of biocompatibility through cytotoxicity and genotoxicity parameters of commercially available toothpastes with whitening effect will be performed using micronucleus assay.
measure: Assessment of participant's satisfaction with treatment and used toothpaste after 60 days of treatment
time frame: 60 days
description: Assessment of participant's satisfaction with treatment and used toothpaste will be performed by prepared questionnaire for the study. Respondents will complete a questionnaire of eating and living habits, too
measure: Assessment of participant's satisfaction with treatment of used toothpaste 30 days after the treatment (90 days from the beginning of treatment)
time frame: 90 days
description: Assessment of participant's satisfaction with treatment and used toothpaste will be performed by prepared questionnaire for the study.
arm group label: Control group
arm group type: Active Comparator
description: A group of participants that will be using toothpaste without tooth whitening ingredients.
arm group label: Whitening toothpaste 1
arm group type: Experimental
description: A group of participants that will be using urea peroxide whitening toothpastes.
arm group label: Whitening toothpaste 2
arm group type: Experimental
description: A group of participants that will be using hydrogen peroxide whitening toothpastes.
arm group label: Whitening toothpaste 3
arm group type: Experimental
description: A group of participants that will be using whitening toothpastes that contain abrasive ingredients.
arm group label: Whitening toothpaste 4
arm group type: Experimental
description: A group of participants that will be using whitening toothpastes that contain enzymes as whitening ingredients.
arm group label: Whitening toothpaste 5
arm group type: Experimental
description: A group of participants that will be using toothpastes that contain an activated charcoal.
intervention type: Other
intervention name: Control group
description: A sample of cells from the buccal mucosa area will be taken with cytological sampling brush and will be fixed on on a microscopy slide and stained with a Feulgen fast green solution. The samples will be analyzed by electron microscopy. Tooth color will be measured, verified and evaluated with a Vita Easyshade V digital spectrophotometer in initial phase, after one month of usage, after two months of usage and one month after the end of usage.
Before using any of the whitening toothpaste under test, every participant will use non whitening toothpaste for one month, twice a day.
Satisfaction and impression with treatment will be recorded with the questionnaires provided for this study.
arm group label: Control group
intervention type: Other
intervention name: Whitening toothpaste 1
description: A sample of cells from the buccal mucosa area will be taken with cytological sampling brush and will be fixed on on a microscopy slide and stained with a Feulgen fast green solution. The samples will be analyzed by electron microscopy. Tooth color will be measured, verified and evaluated with a Vita Easyshade V digital spectrophotometer in initial phase, after one month of usage, after two months of usage and one month after the end of usage.
Before using any of the whitening toothpaste under test, every participant will use non whitening toothpaste for one month, twice a day.
Satisfaction and impression with treatment will be recorded with the questionnaires provided for this study.
arm group label: Whitening toothpaste 1
intervention type: Other
intervention name: Whitening toothpaste 2
description: A sample of cells from the buccal mucosa area will be taken with cytological sampling brush and will be fixed on on a microscopy slide and stained with a Feulgen fast green solution. The samples will be analyzed by electron microscopy. Tooth color will be measured, verified and evaluated with a Vita Easyshade V digital spectrophotometer in initial phase, after one month of usage, after two months of usage and one month after the end of usage.
Before using any of the whitening toothpaste under test, every participant will use non whitening toothpaste for one month, twice a day.
Satisfaction and impression with treatment will be recorded with the questionnaires provided for this study.
arm group label: Whitening toothpaste 2
intervention type: Other
intervention name: Whitening toothpaste 3
description: A sample of cells from the buccal mucosa area will be taken with cytological sampling brush and will be fixed on on a microscopy slide and stained with a Feulgen fast green solution. The samples will be analyzed by electron microscopy. Tooth color will be measured, verified and evaluated with a Vita Easyshade V digital spectrophotometer in initial phase, after one month of usage, after two months of usage and one month after the end of usage.
Before using any of the whitening toothpaste under test, every participant will use non whitening toothpaste for one month, twice a day.
Satisfaction and impression with treatment will be recorded with the questionnaires provided for this study.
arm group label: Whitening toothpaste 3
intervention type: Other
intervention name: Whitening toothpaste 4
description: A sample of cells from the buccal mucosa area will be taken with cytological sampling brush and will be fixed on on a microscopy slide and stained with a Feulgen fast green solution. The samples will be analyzed by electron microscopy. Tooth color will be measured, verified and evaluated with a Vita Easyshade V digital spectrophotometer in initial phase, after one month of usage, after two months of usage and one month after the end of usage.
Before using any of the whitening toothpaste under test, every participant will use non whitening toothpaste for one month, twice a day.
Satisfaction and impression with treatment will be recorded with the questionnaires provided for this study.
arm group label: Whitening toothpaste 4
intervention type: Other
intervention name: Whitening toothpaste 5
description: A sample of cells from the buccal mucosa area will be taken with cytological sampling brush and will be fixed on on a microscopy slide and stained with a Feulgen fast green solution. The samples will be analyzed by electron microscopy. Tooth color will be measured, verified and evaluated with a Vita Easyshade V digital spectrophotometer in initial phase, after one month of usage, after two months of usage and one month after the end of usage.
Before using any of the whitening toothpaste under test, every participant will use non whitening toothpaste for one month, twice a day.
Satisfaction and impression with treatment will be recorded with the questionnaires provided for this study.
arm group label: Whitening toothpaste 5
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: Accepts Healthy Volunteers
facility: 
country: Croatia
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PMID: 1371831
citation: Tadin A, Gavic L, Zeravica A, Ugrin K, Galic N, Zeljezic D. Assessment of cytotoxic and genotoxic effects of conventional and whitening kinds of toothpaste on oral mucosa cells. Acta Odontol Scand. 2018 Jan;76(1):64-70. doi: 10.1080/00016357.2017.1384567. Epub 2017 Sep 29.
PMID: 28959909
citation: Tadin A, Gavic L, Govic T, Galic N, Zorica Vladislavic N, Zeljezic D. In vivo evaluation of fluoride and sodium lauryl sulphate in toothpaste on buccal epithelial cells toxicity. Acta Odontol Scand. 2019 Jul;77(5):386-393. doi: 10.1080/00016357.2019.1577988. Epub 2019 Feb 20. Erratum In: Acta Odontol Scand. 2019 Aug;77(6):483.
PMID: 30784350
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PMID: 23385426
citation: Akarslan ZZ, Sadik B, Erten H, Karabulut E. Dental esthetic satisfaction, received and desired dental treatments for improvement of esthetics. Indian J Dent Res. 2009 Apr-Jun;20(2):195-200. doi: 10.4103/0970-9290.52902.
PMID: 19553722
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responsible party type: Principal Investigator
investigator affiliation: University of Zagreb
investigator full name: Nada Zorica Vladislavic
investigator title: Tooth Whitening Evaluation With Cytotoxic and Genotoxic Effect of Commercial Whitening Toothpastes on Oral Mucosal Cells