<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/NCT04492306</url>
  </required_header>
  <id_info>
    <org_study_id>DMSO Clinical Trial</org_study_id>
    <nct_id>NCT04492306</nct_id>
  </id_info>
  <brief_title>Clinical Evaluation of Dimethyl Sulfoxide Dentin Pre-treatment</brief_title>
  <official_title>In Vivo Clinical Evaluation of Dimethyl Sulfoxide Dentin Pre-treatment Prior to a Two-step Etch and Rinse Adhesive: Randomized Controlled Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Cairo University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>University of Turku</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Cairo University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study is conducted in order to evaluate the clinical effectiveness of 1% DMSO dentin&#xD;
      pre-treatment on the clinical performance of etch and rinse adhesive.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Despite substantial advances in resin-dentin bonding over the past decades, reduction in&#xD;
      bonding effectiveness of currently available dental adhesives remains a major limitation in&#xD;
      modern adhesive dentistry. Hydrolysis of both organic and resin constituents of hybrid layer&#xD;
      persists as impediments in dentin bonding longevity. Since bonding is directly related to the&#xD;
      quality of the formed polymer the resin components play an important role in proper&#xD;
      resin-dentin interaction and in the mechanical properties of the material.&#xD;
&#xD;
      In face of the limitations of most current clinically-feasible bonding protocols and inherent&#xD;
      drawbacks of the etch-and-rinse approach an ideal resin-enveloped collagen scaffold is&#xD;
      unlikely to be produced in a consistent manner. In dentin hybridization, adhesive&#xD;
      infiltration is far from perfect resulting in poorly formed hybrid layers. Replacement of all&#xD;
      70 vol% residual water in etched-dentin with monomers is hardly achieved. For this reason,&#xD;
      the hybrid layer may be considered as the weak link in resin-dentin bonds.&#xD;
&#xD;
      DMSO [(CH3)2SO] is a polar aprotic solvent that dissolves both polar and non-polar compounds.&#xD;
      It is a polyfunctional molecule, with a highly polar S O group and two hydrophobic methyl&#xD;
      groups, fully miscible in most solvents and monomers used in adhesive dentistry. DMSO is&#xD;
      perhaps the best currently known penetration enhancer for medical purposes with the ability&#xD;
      to dissociate the highly crosslinked collagen into a sparser network of apparent fibrils.&#xD;
&#xD;
      The rationale for testing a bonding resin with relatively low DMSO-content is that&#xD;
      incorporation of high DMSO concentrations may hamper the mechanical properties of&#xD;
      dimethacrylate bonding polymers, which in turn could compromise the bonded interface. DMSO's&#xD;
      ability to &quot;biomodify&quot; collagen structure, increasing spaces between collagen microfibrils&#xD;
      and improving dentin wettability support the improved bonding effectiveness even under&#xD;
      dry-conditions. It is evident that this simplified use of DMSO or, to a better extent, its&#xD;
      use as a dentin pretreatment reduced technique sensitivity of the etch-and-rinse approach&#xD;
      concomitantly allowing water removal from the bonded interface by the proposed dry-bonding&#xD;
      technique. Optimized bonding efficiency combined with reduced water-content during dentin&#xD;
      hybridization could greatly contribute to clinical long-term durability.&#xD;
&#xD;
      Nevertheless, further studies are necessary to test such hypothesis. Specially that there is&#xD;
      no clinical study support this theory yet even DMSO had taken the FDA approval many years ago&#xD;
      as a pharmaceutical solvent and has been used in several medications. DMSO caused no or minor&#xD;
      cytotoxic effects on the pulp tissue repair-related activity of odontoblast-like cells.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 17, 2020</start_date>
  <completion_date type="Actual">December 30, 2022</completion_date>
  <primary_completion_date type="Actual">December 30, 2022</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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Outcomes Assessor)</masking>
    <masking_description>In our clinical trial double blinding will be performed, the participants and both assessors (H.M.&amp; N.H.) will be blinded to the type of the material used to reduce performance and ascertainment bias and also reduce biased estimates of treatment effects. The operator cannot be blinded in this trial because of the difference in the application procedures of each restorative material. Therefore, the operator (O.I.) will take care to treat the two allocation groups as equally as possible by standardizing the care of participants, frequency of follow-ups and management of complications.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Biological (change of caries adjacent to the restoration)</measure>
    <time_frame>Day 0, Month 6, Month 12, Month 18</time_frame>
    <description>FDI criteria for evaluation of restorations, percentage score.&#xD;
Score: Properties&#xD;
Clinically excellent/ very good: No secondary or primary caries.&#xD;
Clinically good: Small and Localized 1. Demineralization, 2. Erosion or 3. Abfraction.&#xD;
Clinically sufficient/satisfactory: Larger areas Of 1. Demineralization, 2. Erosion or 3. Abrasion/abfraction, dentine not exposed.&#xD;
Clinically unsatisfactory: Caries with Cavitation and suspected undermining caries, 2. Erosion in dentine, 3. Abrasion/ abfraction in dentine.&#xD;
Clinically poor: Deep caries or exposed dentine that is not accessible for repair of restoration.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Functional (change of marginal adaptation)</measure>
    <time_frame>Day 0, Month 6, Month 12, Month 18</time_frame>
    <description>FDI criteria for evaluation of restorations, percentage score.&#xD;
Score: Properties.&#xD;
Clinically excellent/ very good: Harmonious outline, no gaps, no white or discolored lines.&#xD;
Clinically good: Marginal gap (&lt;150 µm), White lines. Or Small marginal fracture removable by polishing. or Slight ditching, slight step/flashes, minor Irregularities.&#xD;
Clinically sufficient/satisf actory: Gap &lt; 250 µm not removable. Or Several small marginal fractures. Or Major irregularities, ditching or flash, steps.&#xD;
Clinically unsatisfactory: Gap &gt; 250 µm or dentine/base exposed. Or Severe ditching or marginal fractures. or Larger irregularities or steps (repair necessary).&#xD;
Clinically poor: Restoration (complete or partial) is loose but in situ. Or Generalized major gaps or irregularities.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Esthetic (Color match and translucency)</measure>
    <time_frame>Day 0, Month 6, Month 12, Month 18</time_frame>
    <description>FDI criteria for evaluation of restorations, percentage score.&#xD;
Score: Properties&#xD;
Clinically excellent/ very good: Good color match, no difference in shade and/or translucency.&#xD;
Clinically good: Minor deviations in shade and/or translucency.&#xD;
Clinically sufficient/satisfactory: Distinct deviation but acceptable. Does not affect esthetics: 1. more opaque ,2. more translucent ,3. darker,4. brighter.&#xD;
Clinically unsatisfactory: Localized clinically deviation that can be corrected by repair: 1.Too opaque, 2.Too translucent,3. Too dark, 4.Too bright.&#xD;
Clinically poor: Unacceptable. Replacement necessary.</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">24</enrollment>
  <condition>Dental Diseases</condition>
  <arm_group>
    <arm_group_label>3M single bond, etch and rinse adhesive</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>O.I. will clean the labial surface of tooth with polishing paste and brush Roughening of the surface may be needed by diamond point The tooth will be isolated by rubber dam. Apply etchant for 30 s for enamel and 15 s for dentin. Rinse thoroughly with water for 10 s. blot-drying with paper tissue was carefully performed leaving the dentin surface slightly moist.&#xD;
Apply 2 to 3 consecutive coats of the adhesive for 15 s. Gently air for 5 s. Light cure for 10 s. Composite build ups (Filtek Z350 XT, 3 M ESPE, St Paul, MN, USA) were performed in increments and individually light-cured for 40 s. Light curing of all resin materials was performed using a LED device (Bluephase 20i, Ivoclare Vivadent, Schaan, Liechtenstein) delivering 1100 mW/cm2.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>DMSO pre-treatment before 3M single bond application</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The same steps of the comparator group with additional step, after dentin etching and humidity control, dentin pretreatments were performed consisting of active application of 1% DMSO/H2O solutions on etched-dentin followed by blot drying until paper filters no longer absorbed liquids from the bonding surface by capillarity then apply adhesive.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Dimethyl Sulfoxide</intervention_name>
    <description>DMSO [(CH3)2SO] is a polar aprotic solvent that dissolves both polar and non-polar compounds.</description>
    <arm_group_label>DMSO pre-treatment before 3M single bond application</arm_group_label>
    <other_name>1% DMSO</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>3M ESPE Single bond 2</intervention_name>
    <description>Total etch adhesive bond</description>
    <arm_group_label>3M single bond, etch and rinse adhesive</arm_group_label>
    <arm_group_label>DMSO pre-treatment before 3M single bond application</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Filtek Z350 XT, 3 M ESPE, St Paul, MN, USA)</intervention_name>
    <description>Composite Resin</description>
    <arm_group_label>3M single bond, etch and rinse adhesive</arm_group_label>
    <arm_group_label>DMSO pre-treatment before 3M single bond application</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>3m ESPE etch</intervention_name>
    <description>32% phosphoric acid</description>
    <arm_group_label>3M single bond, etch and rinse adhesive</arm_group_label>
    <arm_group_label>DMSO pre-treatment before 3M single bond application</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients with cervical lesions.&#xD;
&#xD;
          -  Co-operative patients approving to participate in the study.&#xD;
&#xD;
          -  Pulp is asymptomatic vital teeth.&#xD;
&#xD;
          -  Presence of favorable occlusion and teeth are in normal contact with the adjacent&#xD;
             teeth.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Xerostomia.&#xD;
&#xD;
          -  Bruxism and visible wear facets in the posterior dentition.&#xD;
&#xD;
          -  Known inability to return for recall appointments.&#xD;
&#xD;
          -  Fractured or visibly cracked candidate tooth.&#xD;
&#xD;
          -  Current desensitizing therapy, including desensitizing dentifrices or other&#xD;
             over-the-counter (OTC) products.&#xD;
&#xD;
          -  Long-term use of anti-inflammatory, analgesic, or psychotropic drugs.&#xD;
&#xD;
          -  Pregnancy or breastfeeding (potential conflicts with recall dates.&#xD;
&#xD;
          -  Allergies to ingredients of resin-based restorative materials.&#xD;
&#xD;
          -  Orthodontic appliance treatment within the previous three months.&#xD;
&#xD;
          -  Abutment teeth for fixed or removable prostheses.&#xD;
&#xD;
          -  Teeth or supporting structures with any symptomatic pathology.&#xD;
&#xD;
          -  Existing periodontal disease or periodontal surgery within the previous three months.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>16 Years</minimum_age>
    <maximum_age>55 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Randa Hafez, Professor</last_name>
    <role>Study Director</role>
    <affiliation>Cairo U</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Faculty of Dentistry, Cairo University</name>
      <address>
        <city>Cairo</city>
        <zip>12613</zip>
        <country>Egypt</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Egypt</country>
  </location_countries>
  <verification_date>February 2023</verification_date>
  <study_first_submitted>July 22, 2020</study_first_submitted>
  <study_first_submitted_qc>July 28, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 30, 2020</study_first_posted>
  <last_update_submitted>February 8, 2023</last_update_submitted>
  <last_update_submitted_qc>February 8, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">February 9, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Cairo University</investigator_affiliation>
    <investigator_full_name>Omar Abdelaziz Ismail</investigator_full_name>
    <investigator_title>Assistant Lecturer of Restorative Dentistry,HUE. Member of the adhesive group of Turku.</investigator_title>
  </responsible_party>
  <keyword>DMSO</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Stomatognathic Diseases</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Dimethyl Sulfoxide</mesh_term>
  </intervention_browse>
  <!-- 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/NCT04492306
org study id: DMSO Clinical Trial
nct id: NCT04492306
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
is us export: No
This study is conducted in order to evaluate the clinical effectiveness of 1% DMSO dentin
      pre-treatment on the clinical performance of etch and rinse adhesive.
Despite substantial advances in resin-dentin bonding over the past decades, reduction in
      bonding effectiveness of currently available dental adhesives remains a major limitation in
      modern adhesive dentistry. Hydrolysis of both organic and resin constituents of hybrid layer
      persists as impediments in dentin bonding longevity. Since bonding is directly related to the
      quality of the formed polymer the resin components play an important role in proper
      resin-dentin interaction and in the mechanical properties of the material.

      In face of the limitations of most current clinically-feasible bonding protocols and inherent
      drawbacks of the etch-and-rinse approach an ideal resin-enveloped collagen scaffold is
      unlikely to be produced in a consistent manner. In dentin hybridization, adhesive
      infiltration is far from perfect resulting in poorly formed hybrid layers. Replacement of all
      70 vol% residual water in etched-dentin with monomers is hardly achieved. For this reason,
      the hybrid layer may be considered as the weak link in resin-dentin bonds.

      DMSO [(CH3)2SO] is a polar aprotic solvent that dissolves both polar and non-polar compounds.
      It is a polyfunctional molecule, with a highly polar S O group and two hydrophobic methyl
      groups, fully miscible in most solvents and monomers used in adhesive dentistry. DMSO is
      perhaps the best currently known penetration enhancer for medical purposes with the ability
      to dissociate the highly crosslinked collagen into a sparser network of apparent fibrils.

      The rationale for testing a bonding resin with relatively low DMSO-content is that
      incorporation of high DMSO concentrations may hamper the mechanical properties of
      dimethacrylate bonding polymers, which in turn could compromise the bonded interface. DMSO's
      ability to "biomodify" collagen structure, increasing spaces between collagen microfibrils
      and improving dentin wettability support the improved bonding effectiveness even under
      dry-conditions. It is evident that this simplified use of DMSO or, to a better extent, its
      use as a dentin pretreatment reduced technique sensitivity of the etch-and-rinse approach
      concomitantly allowing water removal from the bonded interface by the proposed dry-bonding
      technique. Optimized bonding efficiency combined with reduced water-content during dentin
      hybridization could greatly contribute to clinical long-term durability.

      Nevertheless, further studies are necessary to test such hypothesis. Specially that there is
      no clinical study support this theory yet even DMSO had taken the FDA approval many years ago
      as a pharmaceutical solvent and has been used in several medications. DMSO caused no or minor
      cytotoxic effects on the pulp tissue repair-related activity of odontoblast-like cells.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Outcomes Assessor)
masking description: In our clinical trial double blinding will be performed, the participants and both assessors (H.M.& N.H.) will be blinded to the type of the material used to reduce performance and ascertainment bias and also reduce biased estimates of treatment effects. The operator cannot be blinded in this trial because of the difference in the application procedures of each restorative material. Therefore, the operator (O.I.) will take care to treat the two allocation groups as equally as possible by standardizing the care of participants, frequency of follow-ups and management of complications.
measure: Biological (change of caries adjacent to the restoration)
time frame: Day 0, Month 6, Month 12, Month 18
description: FDI criteria for evaluation of restorations, percentage score.
Score: Properties
Clinically excellent/ very good: No secondary or primary caries.
Clinically good: Small and Localized 1. Demineralization, 2. Erosion or 3. Abfraction.
Clinically sufficient/satisfactory: Larger areas Of 1. Demineralization, 2. Erosion or 3. Abrasion/abfraction, dentine not exposed.
Clinically unsatisfactory: Caries with Cavitation and suspected undermining caries, 2. Erosion in dentine, 3. Abrasion/ abfraction in dentine.
Clinically poor: Deep caries or exposed dentine that is not accessible for repair of restoration.
measure: Functional (change of marginal adaptation)
time frame: Day 0, Month 6, Month 12, Month 18
description: FDI criteria for evaluation of restorations, percentage score.
Score: Properties.
Clinically excellent/ very good: Harmonious outline, no gaps, no white or discolored lines.
Clinically good: Marginal gap (<150 µm), White lines. Or Small marginal fracture removable by polishing. or Slight ditching, slight step/flashes, minor Irregularities.
Clinically sufficient/satisf actory: Gap < 250 µm not removable. Or Several small marginal fractures. Or Major irregularities, ditching or flash, steps.
Clinically unsatisfactory: Gap > 250 µm or dentine/base exposed. Or Severe ditching or marginal fractures. or Larger irregularities or steps (repair necessary).
Clinically poor: Restoration (complete or partial) is loose but in situ. Or Generalized major gaps or irregularities.
measure: Esthetic (Color match and translucency)
time frame: Day 0, Month 6, Month 12, Month 18
description: FDI criteria for evaluation of restorations, percentage score.
Score: Properties
Clinically excellent/ very good: Good color match, no difference in shade and/or translucency.
Clinically good: Minor deviations in shade and/or translucency.
Clinically sufficient/satisfactory: Distinct deviation but acceptable. Does not affect esthetics: 1. more opaque ,2. more translucent ,3. darker,4. brighter.
Clinically unsatisfactory: Localized clinically deviation that can be corrected by repair: 1.Too opaque, 2.Too translucent,3. Too dark, 4.Too bright.
Clinically poor: Unacceptable. Replacement necessary.
arm group label: 3M single bond, etch and rinse adhesive
arm group type: Active Comparator
description: O.I. will clean the labial surface of tooth with polishing paste and brush Roughening of the surface may be needed by diamond point The tooth will be isolated by rubber dam. Apply etchant for 30 s for enamel and 15 s for dentin. Rinse thoroughly with water for 10 s. blot-drying with paper tissue was carefully performed leaving the dentin surface slightly moist.
Apply 2 to 3 consecutive coats of the adhesive for 15 s. Gently air for 5 s. Light cure for 10 s. Composite build ups (Filtek Z350 XT, 3 M ESPE, St Paul, MN, USA) were performed in increments and individually light-cured for 40 s. Light curing of all resin materials was performed using a LED device (Bluephase 20i, Ivoclare Vivadent, Schaan, Liechtenstein) delivering 1100 mW/cm2.
arm group label: DMSO pre-treatment before 3M single bond application
arm group type: Experimental
description: The same steps of the comparator group with additional step, after dentin etching and humidity control, dentin pretreatments were performed consisting of active application of 1% DMSO/H2O solutions on etched-dentin followed by blot drying until paper filters no longer absorbed liquids from the bonding surface by capillarity then apply adhesive.
intervention type: Other
intervention name: Dimethyl Sulfoxide
description: DMSO [(CH3)2SO] is a polar aprotic solvent that dissolves both polar and non-polar compounds.
arm group label: DMSO pre-treatment before 3M single bond application
other name: 1% DMSO
intervention type: Other
intervention name: 3M ESPE Single bond 2
description: Total etch adhesive bond
arm group label: 3M single bond, etch and rinse adhesive
arm group label: DMSO pre-treatment before 3M single bond application
intervention type: Other
intervention name: Filtek Z350 XT, 3 M ESPE, St Paul, MN, USA)
description: Composite Resin
arm group label: 3M single bond, etch and rinse adhesive
arm group label: DMSO pre-treatment before 3M single bond application
intervention type: Other
intervention name: 3m ESPE etch
description: 32% phosphoric acid
arm group label: 3M single bond, etch and rinse adhesive
arm group label: DMSO pre-treatment before 3M single bond application
criteria: 
gender: All
minimum age: 16 Years
maximum age: 55 Years
healthy volunteers: No
last name: Randa Hafez, Professor
role: Study Director
affiliation: Cairo U
facility: 
country: Egypt
responsible party type: Principal Investigator
investigator affiliation: Cairo University
investigator full name: Omar Abdelaziz Ismail
investigator title: Assistant Lecturer of Restorative Dentistry,HUE. Member of the adhesive group of Turku.
mesh term: Stomatognathic Diseases
mesh term: Dimethyl Sulfoxide