<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/NCT02967081</url>
  </required_header>
  <id_info>
    <org_study_id>PB_2016-02043</org_study_id>
    <nct_id>NCT02967081</nct_id>
  </id_info>
  <brief_title>Evaluation of Dentinal Fluid for the Presence of Matrix Metalloproteinase 9 (MMP-9) in Pulpal Inflammation</brief_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Zurich</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Zurich</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to determine whether dentinal fluid (tooth fluid) of teeth with&#xD;
      or without a painful inflammatory condition in their nerve (pulp) contain inflammatory&#xD;
      marker.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Objective:&#xD;
&#xD;
      The aim of the study is to use an improved sampling method for collection of MMP-9 to test&#xD;
      the hypothesis that MMP-9 levels are significantly elevated in the dentinal fluid of&#xD;
      symptomatic (painful) human permanent teeth compared to asymptomatic counterparts that need&#xD;
      replacement of a filling, and pulp necrotic teeth. Moreover, the dynamics of MMP-9 expression&#xD;
      after removal of the causative stimulus for pulpitis is to be investigated.&#xD;
&#xD;
      Outcome:&#xD;
&#xD;
      Measuring the total MMP-9 levels of dentinal fluid collected during dental treatment using a&#xD;
      human MMP-9 fluorescent assay.&#xD;
&#xD;
      Measurements and procedures:&#xD;
&#xD;
      Patients attending the day service of the Center of Dental Medicine Zurich will be screened.&#xD;
      Patients matching the inclusion criteria will be asked to participate in the study. Upon&#xD;
      written informed consent, the affected tooth gets anesthetized, isolated with rubber dam and&#xD;
      receives one of the following treatment procedures: caries removal and restoration, tooth&#xD;
      filling replacement and restoration, or root canal treatment (because of irreversible&#xD;
      pulpitis, or pulp necrosis). After caries removal, removal of the defect tooth filling, or&#xD;
      during access cavity preparation, a cellulose membrane (paper point) will be applied with its&#xD;
      blunt end to the dentin for 1 min to collect dentinal fluid. The cellulose membrane will be&#xD;
      stored until the laboratory analysis. Depending on the individual treatment plan of the&#xD;
      patient, the tooth will subsequently receive root canal treatment, its final restoration, or&#xD;
      a temporization with glass-ionomer cement for coverage of the dentinal wound and&#xD;
      reinforcement of the remaining tooth structure. Final restoration of a tooth with composite,&#xD;
      a partial crowns, or full-coverage crown can be technically demanding, time consuming, and&#xD;
      frequently involves multiple patient visits. Teeth that receive root canal treatment, or the&#xD;
      final restoration are sampled once. When a patient with a temporized tooth returns for the&#xD;
      final restoration, the sampling procedure (appliance of a cellulose membrane to the dentin&#xD;
      for 1 min and storage for further analyses) will be repeated. Any further treatment will be&#xD;
      continued without further impairments. The investigation does not alter the treatment plan of&#xD;
      any patient (either participating in one, or two sampling procedures, or in the study at&#xD;
      all).&#xD;
&#xD;
      Number of participants:&#xD;
&#xD;
      Based on a previously performed study (Zehnder et al., 2011), which used a similar&#xD;
      experimental set-up and had 31 participants (2 groups), it is aimed to recruit 60&#xD;
      participants for the current study.&#xD;
&#xD;
      Comparators:&#xD;
&#xD;
      MMP-9 levels in dentinal fluid sampled from teeth with painful (irreversible) pulpitis will&#xD;
      be compared to MMP-9 levels of teeth without clinical signs and symptoms. Moreover, the MMP-9&#xD;
      levels of teeth showing an painless pulpitis (teeth affected by a caries lesion) will be&#xD;
      compared to a repeated sample of the same tooth collected after removal of the caries lesion.&#xD;
&#xD;
      Statistical analysis:&#xD;
&#xD;
      MMP-9 contents in the clinical samples will be determined against a standard curve&#xD;
      (4-parameter logistic curve fit) obtained from the recombinant pro-MMP-9 standard dilution&#xD;
      series. Values between groups will be compared by using Mann-Whitney U test, with the&#xD;
      alpha-type error set at 0.05.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>October 2016</start_date>
  <completion_date type="Actual">October 17, 2017</completion_date>
  <primary_completion_date type="Actual">October 17, 2017</primary_completion_date>
  <study_type>Observational [Patient Registry]</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Other</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <target_duration>10 Days</target_duration>
  <primary_outcome>
    <measure>Total matrix metalloproteinase 9 (MMP-9) level in dentinal fluid</measure>
    <time_frame>Immediately</time_frame>
  </primary_outcome>
  <number_of_groups>4</number_of_groups>
  <enrollment type="Actual">67</enrollment>
  <condition>Pulpitis</condition>
  <arm_group>
    <arm_group_label>Pulp necrosis</arm_group_label>
  </arm_group>
  <arm_group>
    <arm_group_label>Pulpitis (painless)</arm_group_label>
    <description>In this group the dentinal fluid will be sampled/collected twice: Firstly after the removal of the primary caries lesion. Subsequently the cavity will be temporized. Secondly, after removal of the temporary filling material (before final restoration).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Irreversible pulpitis</arm_group_label>
  </arm_group>
  <arm_group>
    <arm_group_label>Normal pulp</arm_group_label>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Collection of dentinal fluid using a cellulose membrane</intervention_name>
    <description>After removal of the caries lesion/filling a cellulose membrane (sterile paper point) will be applied with its blunt end to the dentin for 1 min to collect dentinal fluid.</description>
    <arm_group_label>Irreversible pulpitis</arm_group_label>
    <arm_group_label>Normal pulp</arm_group_label>
    <arm_group_label>Pulp necrosis</arm_group_label>
    <arm_group_label>Pulpitis (painless)</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Adult patients (≥18 y) who attend the University of Zurich, Center of Dental Medicine,&#xD;
        Clinic of Preventive Dentistry, Periodontology and Cariology for dental treatment.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Adult patients who attend the University of Zurich, Center of Dental Medicine, Clinic of&#xD;
        Preventive Dentistry, Periodontology and Cariology that are in need for&#xD;
&#xD;
          -  Treatment of pain related to pulpal inflammation&#xD;
&#xD;
          -  Caries therapy&#xD;
&#xD;
          -  Root canal treatment of a pulp-necrotic tooth&#xD;
&#xD;
          -  Replacement of an defect/fractured filling&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Children or adolescents (≤18 y)&#xD;
&#xD;
          -  Patients who do not agree to participate in the study&#xD;
&#xD;
          -  Patients with general diseases of inflammatory nature (such as diabetes, Crohn's&#xD;
             disease, etc), or diseases affecting the immune-system (immuno-suppression, multiple&#xD;
             morbidities, etc.)&#xD;
&#xD;
          -  Women with known pregnancy&#xD;
&#xD;
          -  Patients not fluent in German or English language&#xD;
&#xD;
          -  Patients who had antibiotic or NSAID intake during the last 14 days&#xD;
&#xD;
          -  Patients who refuse to be examined radiographically.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>University of Zurich, Center of Dental Medicine</name>
      <address>
        <city>Zurich</city>
        <zip>8032</zip>
        <country>Switzerland</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Switzerland</country>
  </location_countries>
  <reference>
    <citation>Zehnder M, Wegehaupt FJ, Attin T. A first study on the usefulness of matrix metalloproteinase 9 from dentinal fluid to indicate pulp inflammation. J Endod. 2011 Jan;37(1):17-20. doi: 10.1016/j.joen.2010.10.003.</citation>
    <PMID>21146069</PMID>
  </reference>
  <verification_date>May 2018</verification_date>
  <study_first_submitted>November 11, 2016</study_first_submitted>
  <study_first_submitted_qc>November 15, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 17, 2016</study_first_posted>
  <last_update_submitted>May 2, 2018</last_update_submitted>
  <last_update_submitted_qc>May 2, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">May 3, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Pulpitis</keyword>
  <keyword>Biomarker</keyword>
  <keyword>Diagnostic</keyword>
  <keyword>Dentinal fluid</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pulpitis</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- 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/NCT02967081
org study id: PB_2016-02043
nct id: NCT02967081
lead sponsor: 
has dmc: No
The purpose of this study is to determine whether dentinal fluid (tooth fluid) of teeth with
      or without a painful inflammatory condition in their nerve (pulp) contain inflammatory
      marker.
Objective:

      The aim of the study is to use an improved sampling method for collection of MMP-9 to test
      the hypothesis that MMP-9 levels are significantly elevated in the dentinal fluid of
      symptomatic (painful) human permanent teeth compared to asymptomatic counterparts that need
      replacement of a filling, and pulp necrotic teeth. Moreover, the dynamics of MMP-9 expression
      after removal of the causative stimulus for pulpitis is to be investigated.

      Outcome:

      Measuring the total MMP-9 levels of dentinal fluid collected during dental treatment using a
      human MMP-9 fluorescent assay.

      Measurements and procedures:

      Patients attending the day service of the Center of Dental Medicine Zurich will be screened.
      Patients matching the inclusion criteria will be asked to participate in the study. Upon
      written informed consent, the affected tooth gets anesthetized, isolated with rubber dam and
      receives one of the following treatment procedures: caries removal and restoration, tooth
      filling replacement and restoration, or root canal treatment (because of irreversible
      pulpitis, or pulp necrosis). After caries removal, removal of the defect tooth filling, or
      during access cavity preparation, a cellulose membrane (paper point) will be applied with its
      blunt end to the dentin for 1 min to collect dentinal fluid. The cellulose membrane will be
      stored until the laboratory analysis. Depending on the individual treatment plan of the
      patient, the tooth will subsequently receive root canal treatment, its final restoration, or
      a temporization with glass-ionomer cement for coverage of the dentinal wound and
      reinforcement of the remaining tooth structure. Final restoration of a tooth with composite,
      a partial crowns, or full-coverage crown can be technically demanding, time consuming, and
      frequently involves multiple patient visits. Teeth that receive root canal treatment, or the
      final restoration are sampled once. When a patient with a temporized tooth returns for the
      final restoration, the sampling procedure (appliance of a cellulose membrane to the dentin
      for 1 min and storage for further analyses) will be repeated. Any further treatment will be
      continued without further impairments. The investigation does not alter the treatment plan of
      any patient (either participating in one, or two sampling procedures, or in the study at
      all).

      Number of participants:

      Based on a previously performed study (Zehnder et al., 2011), which used a similar
      experimental set-up and had 31 participants (2 groups), it is aimed to recruit 60
      participants for the current study.

      Comparators:

      MMP-9 levels in dentinal fluid sampled from teeth with painful (irreversible) pulpitis will
      be compared to MMP-9 levels of teeth without clinical signs and symptoms. Moreover, the MMP-9
      levels of teeth showing an painless pulpitis (teeth affected by a caries lesion) will be
      compared to a repeated sample of the same tooth collected after removal of the caries lesion.

      Statistical analysis:

      MMP-9 contents in the clinical samples will be determined against a standard curve
      (4-parameter logistic curve fit) obtained from the recombinant pro-MMP-9 standard dilution
      series. Values between groups will be compared by using Mann-Whitney U test, with the
      alpha-type error set at 0.05.
observational model: Other
time perspective: Prospective
measure: Total matrix metalloproteinase 9 (MMP-9) level in dentinal fluid
time frame: Immediately
arm group label: Pulp necrosis
arm group label: Pulpitis (painless)
description: In this group the dentinal fluid will be sampled/collected twice: Firstly after the removal of the primary caries lesion. Subsequently the cavity will be temporized. Secondly, after removal of the temporary filling material (before final restoration).
arm group label: Irreversible pulpitis
arm group label: Normal pulp
intervention type: Procedure
intervention name: Collection of dentinal fluid using a cellulose membrane
description: After removal of the caries lesion/filling a cellulose membrane (sterile paper point) will be applied with its blunt end to the dentin for 1 min to collect dentinal fluid.
arm group label: Irreversible pulpitis
arm group label: Normal pulp
arm group label: Pulp necrosis
arm group label: Pulpitis (painless)
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
country: Switzerland
citation: Zehnder M, Wegehaupt FJ, Attin T. A first study on the usefulness of matrix metalloproteinase 9 from dentinal fluid to indicate pulp inflammation. J Endod. 2011 Jan;37(1):17-20. doi: 10.1016/j.joen.2010.10.003.
PMID: 21146069
responsible party type: Sponsor
mesh term: Pulpitis
sharing ipd: No