<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/NCT02188238</url>
  </required_header>
  <id_info>
    <org_study_id>IFR01/2014</org_study_id>
    <nct_id>NCT02188238</nct_id>
  </id_info>
  <brief_title>Effect of Oral Health Ingredients on the Acquired Salivary Pellicle</brief_title>
  <official_title>Effect of Active Ingredients in Oral Health Products on the in Vitro Structure of the Acquired Salivary Pellicle.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Quadram Institute Bioscience</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>GlaxoSmithKline</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Quadram Institute Bioscience</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The aim of this study is to help us understand how saliva forms a thin film inside the&#xD;
      surfaces of the mouth which is known as the salivary pellicle, and how this film helps to&#xD;
      protect our teeth from decay. We know that the thickness and physical properties (viscosity&#xD;
      and mechanical strength) of the salivary pellicle influences:-&#xD;
&#xD;
        -  How we chew and sense the structure of food in our mouth.&#xD;
&#xD;
        -  How we digest the food and extract nutrients from it.&#xD;
&#xD;
        -  Protection against tooth decay and infection.&#xD;
&#xD;
      However, studies have only recently established the different proteins within the pellicle.&#xD;
      The effects of oral care products (e.g. toothpaste, mouthwash etc.) and ingredients they&#xD;
      contain on pellicle formation and removal remain poorly understood. Therefore we need to&#xD;
      understand how the formation of the salivary pellicle is controlled by ingredients it comes&#xD;
      into contact with such as those from food and oral hygiene products (e.g. toothpaste and&#xD;
      mouthwash).&#xD;
&#xD;
      In this study, we are asking volunteers to provide samples of saliva. We will take the saliva&#xD;
      samples back to our labs and measure how they form films under different conditions and&#xD;
      determine the influence of ingredients from oral hygiene on the film forming properties. We&#xD;
      will also measure the protein content of the saliva sample to see how this affects pellicle&#xD;
      formation. Eventually, this information together with knowledge from other studies, should&#xD;
      lead to the development of more effective oral hygiene products.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Saliva contains many proteins and components that contribute to film formation, and we know&#xD;
      that saliva forms complex, structured films on surfaces. The mucosal salivary layer,&#xD;
      comprises of a mobile layer of saliva and an immobile film of salivary proteins adsorbed onto&#xD;
      oral epithelial cells, the &quot;mucosal pellicle&quot;. The salivary film is thin (10-100 µm),&#xD;
      extremely viscoelastic and aids lubrication, influences the sensory perception of food in the&#xD;
      mouth and maintains oral health. The apparent viscoelastic and coating properties of saliva&#xD;
      are in fact mainly due to the formation of an incredibly strong, viscoelastic film at&#xD;
      surfaces and interfaces. The solution viscosity of saliva is actually close to that of water&#xD;
      at high shear rates, but the interfacial viscosity is more than 10,000 times greater than&#xD;
      water, which completely dominates the physical properties of the salivary film as a whole.&#xD;
      This complex structure is driven by molecular scale interactions and is thought to be&#xD;
      responsible for the film forming properties of saliva. What is still unclear are the&#xD;
      fundamental physical and molecular mechanisms underlying the film forming properties of&#xD;
      saliva. Although the viscous and lubricating properties of saliva have often been assigned to&#xD;
      mucins, it appears that isolated mucins do not impart the same lubrication properties as they&#xD;
      do in whole saliva. Other proteins such as statherin have been implicated in enhancing&#xD;
      boundary lubrication. The molecular composition of salivary proteins and the presence of ions&#xD;
      appear to be all important in forming the salivary film. For example, parotid saliva which&#xD;
      contains no mucin is still highly lubricating probably due to its highly visco-elastic&#xD;
      surface layer.&#xD;
&#xD;
      The mucosal pellicle can be mimicked in vitro by adsorbing salivary proteins onto model&#xD;
      surfaces to form interfacial films and has been shown to be highly lubricating. The presence&#xD;
      of polyphenols has been shown to reduce the lubricity of these surface films and correlate&#xD;
      well with their sensory properties. At the Quadram Institute Bioscience (QIB) we have over 20&#xD;
      years' experience studying proteins at interfaces and surfaces, in particular how competitive&#xD;
      adsorption at interfaces of proteins with surfactants and other surface-active components can&#xD;
      affect the composition, structure and stability of the interface, and how this controls the&#xD;
      functionality of the system as a whole. This was applied in a collaborative study on&#xD;
      interfacial salivary films with Kings College London, where we demonstrated the highly&#xD;
      visco-elastic nature of the salivary film and the critical importance of calcium ions in its&#xD;
      formation.&#xD;
&#xD;
      Leading up to this project, the recent postgraduate (PhD) student project at QIB demonstrated&#xD;
      that added calcium can strengthen the salivary pellicle, and that the formation of the&#xD;
      pellicle was a two stage process involving small, surface active proteins in the primary&#xD;
      stage, and larger mucin proteins in the later stage. The study also demonstrated that&#xD;
      reducing pH reduced the integrity of the pellicle, which helps us to understand the role of&#xD;
      the pellicle in preventing acid erosion, and that the addition of various active ingredients&#xD;
      from toothpaste and mouthwash would remove certain proteins from the pellicle, depending on&#xD;
      the type of active ingredient and the surface on which the pellicle was formed. We would like&#xD;
      to extend this project to look at how these active ingredients in mouthwash and toothpaste&#xD;
      affect the structure of the pellicle, and if any combinations of these ingredients have any&#xD;
      additional effect.&#xD;
&#xD;
      Therefore our hypothesis is that active ingredients from toothpastes and mouthwashes can be&#xD;
      used to control the structure of the salivary pellicle through their interactions with either&#xD;
      the surface that the pellicle is adsorbed to, or with the proteins in the pellicle itself.&#xD;
&#xD;
      Understanding these changes to the structure and properties of the salivary film could then&#xD;
      help us understand how the pellicle and the active ingredients protect teeth against decay&#xD;
      and disease.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>July 2014</start_date>
  <completion_date type="Actual">December 31, 2018</completion_date>
  <primary_completion_date type="Actual">September 30, 2018</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Other</observational_model>
    <time_perspective>Other</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Thickness (Depth, nm) of Salivary Films Adsorbed Onto Solid Surfaces</measure>
    <time_frame>Within 4 hours of saliva collection</time_frame>
    <description>The principal output is to determine how ingredients in oral hygiene products affect the way that the protein in saliva forms films on surfaces similar to those found inside the mouth. We will determine the main physical properties of the film such as thickness (nm), adsorbed mass (ng/cm^2), density (ng/cm^3) measured by adsorbing whole mouth saliva onto solid silica surfaces and measuring the above properties of the film using Dual Polarisation Interferometry and a Quartz Crystal Microbalance. The effect of ingredients from oral hygiene products on the above measured parameters will be determined.</description>
  </primary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Actual">10</enrollment>
  <condition>Healthy</condition>
  <arm_group>
    <arm_group_label>Saliva Sample Collection</arm_group_label>
    <description>Collection of stimulated whole mouth saliva . Whole mouth saliva is collected through stimulation by inert gum, and collecting saliva in a sterile tube.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Saliva Sample Collection</intervention_name>
    <description>Saliva samples will be collected from healthy volunteers recruited locally. Stimulated whole mouth saliva is collected through stimulation by inert gum, and collecting the saliva by gently spitting into a sterile tube.</description>
    <arm_group_label>Saliva Sample Collection</arm_group_label>
    <other_name>Stimulated Whole Mouth Saliva</other_name>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Apparently healthy volunteers from the local community able to donate saliva samples&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Apparently Healthy&#xD;
&#xD;
          -  Age: 18 - 65y&#xD;
&#xD;
          -  Gender: Male or Female&#xD;
&#xD;
          -  Non-smokers&#xD;
&#xD;
          -  There are no restrictions regarding dietary habits&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  have known diabetes&#xD;
&#xD;
          -  have any medical history of Tuberculosis or Hepatitis&#xD;
&#xD;
          -  have depressed or elevated blood pressure measurements (&lt;90/50 or &lt;95/50 if&#xD;
             symptomatic or &gt;160/100).&#xD;
&#xD;
          -  are currently undergoing any medical investigations&#xD;
&#xD;
          -  have undergone any dental or mouth surgery, or tongue piercing within the last six&#xD;
             weeks&#xD;
&#xD;
          -  take any medication which may affect saliva production&#xD;
&#xD;
          -  have any ongoing or chronic dental or mouth problems that may influence saliva&#xD;
             composition&#xD;
&#xD;
          -  have jaw or chewing problems which may be exacerbated by the saliva collection&#xD;
             procedure&#xD;
&#xD;
          -  are related to someone in the study team i.e. spouse, partner or immediate family&#xD;
             member&#xD;
&#xD;
          -  are pregnant, planning to become pregnant, or are currently breastfeeding.&#xD;
&#xD;
          -  are not prepared to remove any tongue &quot;piercings&quot; prior to the saliva collection&#xD;
             procedure.&#xD;
&#xD;
          -  If results of the clinical screening which indicate, or are judged by the Human&#xD;
             Nutrition Unit's (HNU) Medical Advisor to be indicative of, a health problem which&#xD;
             compromise the well-being of the volunteer if they participated, or which would affect&#xD;
             the study data.&#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>
  <overall_official>
    <last_name>Peter J Wilde, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Quadram Institute Bioscience</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Quadram Institute Bioscience</name>
      <address>
        <city>Norwich</city>
        <state>Norfolk</state>
        <zip>NR4 7UA</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <link>
    <url>http://www.ifr.ac.uk</url>
    <description>Link to IFR homepage</description>
  </link>
  <link>
    <url>http://www.ifr.ac.uk/profile/peter-wilde.asp</url>
    <description>Principal Investigator homepage</description>
  </link>
  <reference>
    <citation>Ash A, Burnett GR, Parker R, Ridout MJ, Rigby NM, Wilde PJ. Structural characterisation of parotid and whole mouth salivary pellicles adsorbed onto DPI and QCMD hydroxyapatite sensors. Colloids Surf B Biointerfaces. 2014 Apr 1;116:603-11. doi: 10.1016/j.colsurfb.2013.10.024. Epub 2013 Nov 12.</citation>
    <PMID>24269053</PMID>
  </reference>
  <reference>
    <citation>Ash A, Ridout MJ, Parker R, Mackie AR, Burnett GR, Wilde PJ. Effect of calcium ions on in vitro pellicle formation from parotid and whole saliva. Colloids Surf B Biointerfaces. 2013 Feb 1;102:546-53. doi: 10.1016/j.colsurfb.2012.08.048. Epub 2012 Sep 7.</citation>
    <PMID>23104024</PMID>
  </reference>
  <verification_date>October 2017</verification_date>
  <study_first_submitted>July 10, 2014</study_first_submitted>
  <study_first_submitted_qc>July 10, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 11, 2014</study_first_posted>
  <last_update_submitted>March 6, 2019</last_update_submitted>
  <last_update_submitted_qc>March 6, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">March 7, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>saliva</keyword>
  <keyword>protein</keyword>
  <keyword>oral health</keyword>
  <keyword>film</keyword>
  <keyword>pellicle</keyword>
  <!-- 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/NCT02188238
org study id: IFR01/2014
nct id: NCT02188238
lead sponsor: 
collaborator: 
has dmc: No
The aim of this study is to help us understand how saliva forms a thin film inside the
      surfaces of the mouth which is known as the salivary pellicle, and how this film helps to
      protect our teeth from decay. We know that the thickness and physical properties (viscosity
      and mechanical strength) of the salivary pellicle influences:-

        -  How we chew and sense the structure of food in our mouth.

        -  How we digest the food and extract nutrients from it.

        -  Protection against tooth decay and infection.

      However, studies have only recently established the different proteins within the pellicle.
      The effects of oral care products (e.g. toothpaste, mouthwash etc.) and ingredients they
      contain on pellicle formation and removal remain poorly understood. Therefore we need to
      understand how the formation of the salivary pellicle is controlled by ingredients it comes
      into contact with such as those from food and oral hygiene products (e.g. toothpaste and
      mouthwash).

      In this study, we are asking volunteers to provide samples of saliva. We will take the saliva
      samples back to our labs and measure how they form films under different conditions and
      determine the influence of ingredients from oral hygiene on the film forming properties. We
      will also measure the protein content of the saliva sample to see how this affects pellicle
      formation. Eventually, this information together with knowledge from other studies, should
      lead to the development of more effective oral hygiene products.
Saliva contains many proteins and components that contribute to film formation, and we know
      that saliva forms complex, structured films on surfaces. The mucosal salivary layer,
      comprises of a mobile layer of saliva and an immobile film of salivary proteins adsorbed onto
      oral epithelial cells, the "mucosal pellicle". The salivary film is thin (10-100 µm),
      extremely viscoelastic and aids lubrication, influences the sensory perception of food in the
      mouth and maintains oral health. The apparent viscoelastic and coating properties of saliva
      are in fact mainly due to the formation of an incredibly strong, viscoelastic film at
      surfaces and interfaces. The solution viscosity of saliva is actually close to that of water
      at high shear rates, but the interfacial viscosity is more than 10,000 times greater than
      water, which completely dominates the physical properties of the salivary film as a whole.
      This complex structure is driven by molecular scale interactions and is thought to be
      responsible for the film forming properties of saliva. What is still unclear are the
      fundamental physical and molecular mechanisms underlying the film forming properties of
      saliva. Although the viscous and lubricating properties of saliva have often been assigned to
      mucins, it appears that isolated mucins do not impart the same lubrication properties as they
      do in whole saliva. Other proteins such as statherin have been implicated in enhancing
      boundary lubrication. The molecular composition of salivary proteins and the presence of ions
      appear to be all important in forming the salivary film. For example, parotid saliva which
      contains no mucin is still highly lubricating probably due to its highly visco-elastic
      surface layer.

      The mucosal pellicle can be mimicked in vitro by adsorbing salivary proteins onto model
      surfaces to form interfacial films and has been shown to be highly lubricating. The presence
      of polyphenols has been shown to reduce the lubricity of these surface films and correlate
      well with their sensory properties. At the Quadram Institute Bioscience (QIB) we have over 20
      years' experience studying proteins at interfaces and surfaces, in particular how competitive
      adsorption at interfaces of proteins with surfactants and other surface-active components can
      affect the composition, structure and stability of the interface, and how this controls the
      functionality of the system as a whole. This was applied in a collaborative study on
      interfacial salivary films with Kings College London, where we demonstrated the highly
      visco-elastic nature of the salivary film and the critical importance of calcium ions in its
      formation.

      Leading up to this project, the recent postgraduate (PhD) student project at QIB demonstrated
      that added calcium can strengthen the salivary pellicle, and that the formation of the
      pellicle was a two stage process involving small, surface active proteins in the primary
      stage, and larger mucin proteins in the later stage. The study also demonstrated that
      reducing pH reduced the integrity of the pellicle, which helps us to understand the role of
      the pellicle in preventing acid erosion, and that the addition of various active ingredients
      from toothpaste and mouthwash would remove certain proteins from the pellicle, depending on
      the type of active ingredient and the surface on which the pellicle was formed. We would like
      to extend this project to look at how these active ingredients in mouthwash and toothpaste
      affect the structure of the pellicle, and if any combinations of these ingredients have any
      additional effect.

      Therefore our hypothesis is that active ingredients from toothpastes and mouthwashes can be
      used to control the structure of the salivary pellicle through their interactions with either
      the surface that the pellicle is adsorbed to, or with the proteins in the pellicle itself.

      Understanding these changes to the structure and properties of the salivary film could then
      help us understand how the pellicle and the active ingredients protect teeth against decay
      and disease.
observational model: Other
time perspective: Other
measure: Thickness (Depth, nm) of Salivary Films Adsorbed Onto Solid Surfaces
time frame: Within 4 hours of saliva collection
description: The principal output is to determine how ingredients in oral hygiene products affect the way that the protein in saliva forms films on surfaces similar to those found inside the mouth. We will determine the main physical properties of the film such as thickness (nm), adsorbed mass (ng/cm^2), density (ng/cm^3) measured by adsorbing whole mouth saliva onto solid silica surfaces and measuring the above properties of the film using Dual Polarisation Interferometry and a Quartz Crystal Microbalance. The effect of ingredients from oral hygiene products on the above measured parameters will be determined.
arm group label: Saliva Sample Collection
description: Collection of stimulated whole mouth saliva . Whole mouth saliva is collected through stimulation by inert gum, and collecting saliva in a sterile tube.
intervention type: Other
intervention name: Saliva Sample Collection
description: Saliva samples will be collected from healthy volunteers recruited locally. Stimulated whole mouth saliva is collected through stimulation by inert gum, and collecting the saliva by gently spitting into a sterile tube.
arm group label: Saliva Sample Collection
other name: Stimulated Whole Mouth Saliva
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Peter J Wilde, PhD
role: Principal Investigator
affiliation: Quadram Institute Bioscience
facility: 
country: United Kingdom
url: http://www.ifr.ac.uk
description: Link to IFR homepage
url: http://www.ifr.ac.uk/profile/peter-wilde.asp
description: Principal Investigator homepage
citation: Ash A, Burnett GR, Parker R, Ridout MJ, Rigby NM, Wilde PJ. Structural characterisation of parotid and whole mouth salivary pellicles adsorbed onto DPI and QCMD hydroxyapatite sensors. Colloids Surf B Biointerfaces. 2014 Apr 1;116:603-11. doi: 10.1016/j.colsurfb.2013.10.024. Epub 2013 Nov 12.
PMID: 24269053
citation: Ash A, Ridout MJ, Parker R, Mackie AR, Burnett GR, Wilde PJ. Effect of calcium ions on in vitro pellicle formation from parotid and whole saliva. Colloids Surf B Biointerfaces. 2013 Feb 1;102:546-53. doi: 10.1016/j.colsurfb.2012.08.048. Epub 2012 Sep 7.
PMID: 23104024
responsible party type: Sponsor