<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/NCT01714024</url>
  </required_header>
  <id_info>
    <org_study_id>ZMU 11-2539</org_study_id>
    <nct_id>NCT01714024</nct_id>
  </id_info>
  <brief_title>Dental Implant Study Comparing Two Types of Metals Used for Dental Implants</brief_title>
  <acronym>ZMU</acronym>
  <official_title>A Molecular and Cellular Comparison of Bone Inductive Properties Of Trabecular Metal® Vs. Titanium Among Healthy, Diabetic, and Osteopenic Subjects</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of North Carolina, Chapel Hill</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Zimmer Dental</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>University of North Carolina, Chapel Hill</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this research study is to compare the healing differences of two metals&#xD;
      (trabecular vs. standard titanium) that are used for dental implants. In addition;&#xD;
      investigators will be examine these differences in the gene expression profiles in subjects&#xD;
      with three conditions associated with delayed healing: diabetes and osteoporosis.&#xD;
&#xD;
      The study will last at least 11 weeks consisting of 6 appointments. All visits will be&#xD;
      carried out at the GO Health Center within the UNC School of Dentistry. Visits will last&#xD;
      between 30 minutes to 3 hours depending on the particular visit.&#xD;
&#xD;
      The visits will consist of: Obtaining consent, doing a health history, measuring vital signs,&#xD;
      doing dental exams of the teeth and gums, collecting samples of saliva dental radiographs&#xD;
      (X-rays), a teeth cleaning, having 4 temporary mini test cylinders placed in areas of the&#xD;
      lower jaw where teeth are missing and implant surgery to place up to four permanent implants.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The plan is to recruit subjects into 3 groups: 1) systemically healthy, 2) subjects with&#xD;
      diabetes (ADA classification determined by glycosylated hemoglobin A1C levels), and 3)&#xD;
      subjects with osteoporosis (limited to those on either no drugs or oral bisphosphonates&#xD;
      only). All subjects recruited will have already been approved and treatment planned for&#xD;
      implant placement by non-study personnel to avoid any potential conflict of interest. All&#xD;
      subjects will have mandibular radiographs that show edentulous ridge areas that provide&#xD;
      enough alveolar ridge space to place two test cylinders (each approximately 2.9-3 x 5mm) on&#xD;
      each side of the mandible. One side will have two titanium test cylinders and the&#xD;
      contralateral side will have two trabecular metal test cylinders. After placement of these 4&#xD;
      test cylinders, one will be removed contra laterally from each side at weeks 2 and 4 of&#xD;
      healing. Thus, by 28 days all test cylinders will be removed.&#xD;
&#xD;
      It has been our experience that each cylinder after removal will contain enough cells to&#xD;
      provide approximately 10-20μg of total RNA. This quantity of total RNA is sufficient to run&#xD;
      an Affymetrix chip and have enough mRNA for PCR confirmation. Sampling at 3 days after&#xD;
      placement is too soon, as it does not provide adequate mRNA for the analysis, since the clot&#xD;
      has not become remodeled or adequately organized to be cellular. Thus, by 1 week organization&#xD;
      of the osseous healing will have begun and at week 2 it will be beginning to mature. The week&#xD;
      2 sampling time point) will provide us with early molecular kinetics of the healing response&#xD;
      to compare the two metal surfaces and the differences in gene expression that may be&#xD;
      associated with diabetes and osteoporosis. At weeks 2 and 4 the test cylinders will be&#xD;
      removed using a 5.0 mm diameter tissue punch and a 5 mm trephine drill. Investigators will&#xD;
      select 18 random patients (6 subjects per group) to provide (two test cylinders for each, 36&#xD;
      samples) for histology. Investigators will use the trephine drill to remove the 4 week test&#xD;
      cylinders in all 3 groups of subjects. In all cases, a subject is eligible for this study by&#xD;
      being pretreatment planned to receive a permanent implant bilaterally, which will be placed&#xD;
      at donor sites. According to the participant's individual treatment plan, after test&#xD;
      cylinders are removed, each site will receive an implant using either a standard 4.1 or 4.7&#xD;
      mm tapered screw vent design implant. The removed test cylinders will be briefly rinsed in&#xD;
      saline and prepared chair side for either mRNA extraction or for histology.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>October 2012</start_date>
  <completion_date type="Actual">May 2015</completion_date>
  <primary_completion_date type="Actual">May 2015</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Fold Change in Gene Expression Comparing Trabecular Metal to Standard Titanium.</measure>
    <time_frame>2 weeks &amp; 4 weeks post placement</time_frame>
    <description>Samples were analyzed comparing the osteogenic potential associated with titanium and porous tantalum dental implants (cylinders) at 2 and 4 weeks using transcriptome analyses. The primary outcome data are displayed showing the Average Delta ∆ (Ct) for osteogenic genes relative to the housekeeping markers. The numerical value of the CT is inversely related to the amount of amplicon in the reaction (i.e., the lower the CT, the greater the amount of amplicon).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Group Based Differences (i.e. Healthy, Osteopenic and Diabetic) in Gene Expression Using Fold Changes Between Titanium and Trabecular at 4 Weeks.</measure>
    <time_frame>4 weeks</time_frame>
    <description>Findings from expression arrays will be used to perform quantitative PCR analyses using SAB Superarrays (SuperArray GEArray), to enable a quantitativeassay of mRNA levels of specific inflammatory and growth factor molecules</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">42</enrollment>
  <condition>Tooth Replacement</condition>
  <arm_group>
    <arm_group_label>Healthy Volunteers</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects who are non-diabetic, with no history of smoking within the past two years and no metabolic bone disease diagnosis.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Diabetic Subjects</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects must have Type 2 diabetes mellitus as diagnosed by a physician or in medication history. The condition must be currently diagnosed and treated by medications and/or insulin.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Osteopenic Subjects</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects must be diagnosed with osteoporosis or osteopenia and must be currently under the care of a physician and treatment with oral bisphosphonates</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Zimmer Trabecular Metal Test Cylinder</intervention_name>
    <description>For all subjects 2 titanium and 2 trabecular 2.9-3.0 mm x 5 mm test cylinders will be implanted in alveolar bone. One of each type will be removed at 2 weeks. The remaining two will be removed at 4 weeks.</description>
    <arm_group_label>Diabetic Subjects</arm_group_label>
    <arm_group_label>Healthy Volunteers</arm_group_label>
    <arm_group_label>Osteopenic Subjects</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Zimmer Titanium Test Cylinder</intervention_name>
    <description>For all subjects 2 titanium and 2 trabecular 2.9-3.0 mm x 5 mm test cylinders will be implanted in alveolar bone. One of each type will be removed at 2 weeks. The remaining two will be removed at 4 weeks.</description>
    <arm_group_label>Diabetic Subjects</arm_group_label>
    <arm_group_label>Healthy Volunteers</arm_group_label>
    <arm_group_label>Osteopenic Subjects</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Subjects must be adult males or females age 21 to 80 years (inclusive).&#xD;
&#xD;
          -  Subjects must be able and willing to follow study procedures and instructions in&#xD;
             English.&#xD;
&#xD;
          -  Subjects must have read, understood and signed an informed consent form in English.&#xD;
&#xD;
          -  Subjects must have at least four mandibular implants as their future treatment needs.&#xD;
&#xD;
        Subjects must meet one of the following categories to be considered for enrollment:&#xD;
&#xD;
          -  Group 1 (control): Subjects must be non-diabetic, no history of smoking within the&#xD;
             last two years and no metabolic bone disease diagnosis.&#xD;
&#xD;
          -  Group 2 (diabetic): Subjects must have Type 2 diabetes mellitus as diagnosed by a&#xD;
             physician or in medication history. The condition must be currently diagnosed and&#xD;
             treated by medications and/or insulin. An HbA1C test performed either within past 3&#xD;
             months must be available or one will be done at the first visit by study personnel.&#xD;
             Subjects must have no history of smoking within the last two years nor have any&#xD;
             diagnosis of metabolic bone disease.&#xD;
&#xD;
          -  Group 3 (Osteoporosis or osteopenia): Subjects must be diagnosed with osteoporosis or&#xD;
             osteopenia and must be currently under the care of a physician and treatment with oral&#xD;
             bisphosphonates. Subjects must have never had intravenous (IV) bisphosphonates.&#xD;
             Subjects in this group must be non-diabetic and no history of smoking within the last&#xD;
             2 years.&#xD;
&#xD;
        Subjects undergoing test cylinder placement should be in adequate periodontal health prior&#xD;
        to implant placement. This includes having probing depth ≤ 4 mm for all remaining teeth at&#xD;
        the same quadrant of the proposed cylinder placement. Patients with periodontal probing&#xD;
        sites with probing depths of up to 5 mm may also be included if bleeding on probing in&#xD;
        these sites is absent. Each subject should be considered to be periodontally stable prior&#xD;
        to receiving test cylinders.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Individuals who have a chronic disease with oral manifestations.&#xD;
&#xD;
          -  Individuals who exhibit gross oral pathology.&#xD;
&#xD;
          -  The use of either antibiotics or chronic use of NSAIDs within 1 month prior to&#xD;
             screening examination.&#xD;
&#xD;
          -  Individuals that require antibiotic prophylaxis prior to dental treatment.&#xD;
&#xD;
          -  Chronic treatment (i.e. two weeks or more) with any medication known to affect&#xD;
             periodontal status (e.g. phenytoin, calcium antagonists, cyclosporine, Coumadin)&#xD;
             within 1 month prior to screening examination.&#xD;
&#xD;
          -  Systemic conditions, except diabetes, osteoporosis and osteopenia that are known to&#xD;
             affect periodontal status.&#xD;
&#xD;
          -  Individual with uncontrolled parafunctional habits, such as clenching and bruxing on&#xD;
             objects, that could adversely impact implant survival&#xD;
&#xD;
          -  Individuals with a history of intravenous bisphosphonates Individuals with active&#xD;
             infectious diseases such as hepatitis, HIV or tuberculosis.&#xD;
&#xD;
          -  Individuals with a current tobacco use history.&#xD;
&#xD;
          -  Individuals who are known to be pregnant, breastfeeding or planning to become pregnant&#xD;
             within 3 months.&#xD;
&#xD;
          -  Individuals with blood disorders and /or currently taking anticoagulants medications,&#xD;
             unless he or she can provide a current International normalized ratio (INR) showing&#xD;
             normal (0.8 - 2.0) values.&#xD;
&#xD;
          -  Individuals receiving any therapy known to affect healing, such as high dose&#xD;
             corticosteroids, radiation therapy or chemotherapy.&#xD;
&#xD;
          -  Individuals allergic to topical or local anesthesia&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>21 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Steven Offenbacher, DDS, PhD, MMSc</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of North Carolina School of Dentistry</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>General &amp; Oral Health Center</name>
      <address>
        <city>Chapel Hill</city>
        <state>North Carolina</state>
        <zip>27599</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://gohealthcenter.org/</url>
    <description>This website is affiliated with the UNC School of Dentistry and is primarily used to inform potential participants about research being done within the General and Oral Health Center.</description>
  </link>
  <verification_date>January 2016</verification_date>
  <study_first_submitted>October 17, 2012</study_first_submitted>
  <study_first_submitted_qc>October 24, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 25, 2012</study_first_posted>
  <results_first_submitted>February 17, 2017</results_first_submitted>
  <results_first_submitted_qc>June 12, 2017</results_first_submitted_qc>
  <results_first_posted type="Actual">July 12, 2017</results_first_posted>
  <last_update_submitted>September 11, 2017</last_update_submitted>
  <last_update_submitted_qc>September 11, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">October 12, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Dental</keyword>
  <keyword>Implant</keyword>
  <keyword>UNC Dental School</keyword>
  <keyword>Trabecular Metal</keyword>
  <keyword>Titanium</keyword>
  <keyword>Healthy Volunteers</keyword>
  <keyword>Diabetic</keyword>
  <keyword>Osteopenic</keyword>
  <keyword>Bone Inductive Properties</keyword>
  <keyword>Osseous Healing</keyword>
  <keyword>GO Health</keyword>
  <keyword>Offenbacher</keyword>
  <keyword>Zimmer Dental, Inc.</keyword>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Healthy Volunteers</title>
          <description>Subjects who are non-diabetic, with no history of smoking within the past two years and no metabolic bone disease diagnosis.&#xD;
Zimmer Trabecular Metal Test Cylinder: For all subjects 2 titanium and 2 trabecular 2.9-3.0 mm x 5 mm test cylinders will be implanted in alveolar bone. One of each type will be removed at 2 weeks. The remaining two will be removed at 4 weeks.&#xD;
Zimmer Titanium Test Cylinder: For all subjects 2 titanium and 2 trabecular 2.9-3.0 mm x 5 mm test cylinders will be implanted in alveolar bone. One of each type will be removed at 2 weeks. The remaining two will be removed at 4 weeks.</description>
        </group>
        <group group_id="P2">
          <title>Diabetic Subjects</title>
          <description>Subjects must have Type 2 diabetes mellitus as diagnosed by a physician or in medication history. The condition must be currently diagnosed and treated by medications and/or insulin.&#xD;
Zimmer Trabecular Metal Test Cylinder: For all subjects 2 titanium and 2 trabecular 2.9-3.0 mm x 5 mm test cylinders will be implanted in alveolar bone. One of each type will be removed at 2 weeks. The remaining two will be removed at 4 weeks.&#xD;
Zimmer Titanium Test Cylinder: For all subjects 2 titanium and 2 trabecular 2.9-3.0 mm x 5 mm test cylinders will be implanted in alveolar bone. One of each type will be removed at 2 weeks. The remaining two will be removed at 4 weeks.</description>
        </group>
        <group group_id="P3">
          <title>Osteopenic Subjects</title>
          <description>Subjects must be diagnosed with osteoporosis or osteopenia and must be currently under the care of a physician and treatment with oral bisphosphonates&#xD;
Zimmer Trabecular Metal Test Cylinder: For all subjects 2 titanium and 2 trabecular 2.9-3.0 mm x 5 mm test cylinders will be implanted in alveolar bone. One of each type will be removed at 2 weeks. The remaining two will be removed at 4 weeks.&#xD;
Zimmer Titanium Test Cylinder: For all subjects 2 titanium and 2 trabecular 2.9-3.0 mm x 5 mm test cylinders will be implanted in alveolar bone. One of each type will be removed at 2 weeks. The remaining two will be removed at 4 weeks.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="13"/>
                <participants group_id="P2" count="18"/>
                <participants group_id="P3" count="11"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="12"/>
                <participants group_id="P2" count="12"/>
                <participants group_id="P3" count="8"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="6"/>
                <participants group_id="P3" count="3"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Healthy Volunteers</title>
          <description>Subjects who are non-diabetic, with no history of smoking within the past two years and no metabolic bone disease diagnosis.&#xD;
Zimmer Trabecular Metal Test Cylinder: For all subjects 2 titanium and 2 trabecular 2.9-3.0 mm x 5 mm test cylinders will be implanted in alveolar bone. One of each type will be removed at 2 weeks. The remaining two will be removed at 4 weeks.&#xD;
Zimmer Titanium Test Cylinder: For all subjects 2 titanium and 2 trabecular 2.9-3.0 mm x 5 mm test cylinders will be implanted in alveolar bone. One of each type will be removed at 2 weeks. The remaining two will be removed at 4 weeks.</description>
        </group>
        <group group_id="B2">
          <title>Diabetic Subjects</title>
          <description>Subjects must have Type 2 diabetes mellitus as diagnosed by a physician or in medication history. The condition must be currently diagnosed and treated by medications and/or insulin.&#xD;
Zimmer Trabecular Metal Test Cylinder: For all subjects 2 titanium and 2 trabecular 2.9-3.0 mm x 5 mm test cylinders will be implanted in alveolar bone. One of each type will be removed at 2 weeks. The remaining two will be removed at 4 weeks.&#xD;
Zimmer Titanium Test Cylinder: For all subjects 2 titanium and 2 trabecular 2.9-3.0 mm x 5 mm test cylinders will be implanted in alveolar bone. One of each type will be removed at 2 weeks. The remaining two will be removed at 4 weeks.</description>
        </group>
        <group group_id="B3">
          <title>Osteopenic Subjects</title>
          <description>Subjects must be diagnosed with osteoporosis or osteopenia and must be currently under the care of a physician and treatment with oral bisphosphonates&#xD;
Zimmer Trabecular Metal Test Cylinder: For all subjects 2 titanium and 2 trabecular 2.9-3.0 mm x 5 mm test cylinders will be implanted in alveolar bone. One of each type will be removed at 2 weeks. The remaining two will be removed at 4 weeks.&#xD;
Zimmer Titanium Test Cylinder: For all subjects 2 titanium and 2 trabecular 2.9-3.0 mm x 5 mm test cylinders will be implanted in alveolar bone. One of each type will be removed at 2 weeks. The remaining two will be removed at 4 weeks.</description>
        </group>
        <group group_id="B4">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="12"/>
            <count group_id="B2" value="12"/>
            <count group_id="B3" value="8"/>
            <count group_id="B4" value="32"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="3"/>
                    <measurement group_id="B4" value="16"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="5"/>
                    <measurement group_id="B4" value="16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="59.33" lower_limit="39" upper_limit="75"/>
                    <measurement group_id="B2" value="64.33" lower_limit="54" upper_limit="71"/>
                    <measurement group_id="B3" value="66.38" lower_limit="59" upper_limit="76"/>
                    <measurement group_id="B4" value="64.22" lower_limit="39" upper_limit="76"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="8"/>
                    <measurement group_id="B4" value="20"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                    <measurement group_id="B2" value="12"/>
                    <measurement group_id="B3" value="12"/>
                    <measurement group_id="B4" value="36"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Fold Change in Gene Expression Comparing Trabecular Metal to Standard Titanium.</title>
        <description>Samples were analyzed comparing the osteogenic potential associated with titanium and porous tantalum dental implants (cylinders) at 2 and 4 weeks using transcriptome analyses. The primary outcome data are displayed showing the Average Delta ∆ (Ct) for osteogenic genes relative to the housekeeping markers. The numerical value of the CT is inversely related to the amount of amplicon in the reaction (i.e., the lower the CT, the greater the amount of amplicon).</description>
        <time_frame>2 weeks &amp; 4 weeks post placement</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Healthy/Tantalum</title>
            <description>Subjects who are non-diabetic, with no history of smoking within the past two years and no metabolic bone disease diagnosis.&#xD;
For all subjects 2 titanium and 2 trabecular 2.9-3.0 mm x 5 mm test cylinders were implanted in alveolar bone. One of each type will be removed at 2 weeks. The remaining two were removed at 4 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Healthy/Titanium</title>
            <description>Subjects who are non-diabetic, with no history of smoking within the past two years and no metabolic bone disease diagnosis.&#xD;
For all subjects 2 titanium and 2 trabecular 2.9-3.0 mm x 5 mm test cylinders were implanted in alveolar bone. One of each type will be removed at 2 weeks. The remaining two were removed at 4 weeks.</description>
          </group>
          <group group_id="O3">
            <title>Osteopenic/Tantalum</title>
            <description>Subjects must be diagnosed with osteoporosis or osteopenia, non-diabetic, with no history of smoking within the past two years&#xD;
For all subjects 2 titanium and 2 trabecular 2.9-3.0 mm x 5 mm test cylinders were implanted in alveolar bone. One of each type will be removed at 2 weeks. The remaining two were removed at 4 weeks.</description>
          </group>
          <group group_id="O4">
            <title>Osteopenic/Titanium</title>
            <description>Subjects must be diagnosed with osteoporosis or osteopenia, non-diabetic, with no history of smoking within the past two years&#xD;
For all subjects 2 titanium and 2 trabecular 2.9-3.0 mm x 5 mm test cylinders were implanted in alveolar bone. One of each type will be removed at 2 weeks. The remaining two were removed at 4 weeks.</description>
          </group>
          <group group_id="O5">
            <title>Diabetic/Tantalum</title>
            <description>Subjects who are diabetic, with no history of smoking within the past two years and no metabolic bone disease diagnosis&#xD;
For all subjects 2 titanium and 2 trabecular 2.9-3.0 mm x 5 mm test cylinders were implanted in alveolar bone. One of each type will be removed at 2 weeks. The remaining two were removed at 4 weeks.</description>
          </group>
          <group group_id="O6">
            <title>Diabetic/Titanium</title>
            <description>Subjects who are diabetic, with no history of smoking within the past two years and no metabolic bone disease diagnosis&#xD;
For all subjects 2 titanium and 2 trabecular 2.9-3.0 mm x 5 mm test cylinders were implanted in alveolar bone. One of each type will be removed at 2 weeks. The remaining two were removed at 4 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Fold Change in Gene Expression Comparing Trabecular Metal to Standard Titanium.</title>
          <description>Samples were analyzed comparing the osteogenic potential associated with titanium and porous tantalum dental implants (cylinders) at 2 and 4 weeks using transcriptome analyses. The primary outcome data are displayed showing the Average Delta ∆ (Ct) for osteogenic genes relative to the housekeeping markers. The numerical value of the CT is inversely related to the amount of amplicon in the reaction (i.e., the lower the CT, the greater the amount of amplicon).</description>
          <units>Average Delta ∆ (Ct)</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="12"/>
                <count group_id="O2" value="12"/>
                <count group_id="O3" value="8"/>
                <count group_id="O4" value="8"/>
                <count group_id="O5" value="12"/>
                <count group_id="O6" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>BMP2 (2 weeks)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.6758" spread="0.12"/>
                    <measurement group_id="O2" value="9.2208" spread="1.15"/>
                    <measurement group_id="O3" value="4.6085" spread="2.67"/>
                    <measurement group_id="O4" value="5.2331" spread="1.69"/>
                    <measurement group_id="O5" value="7.1463" spread="1.67"/>
                    <measurement group_id="O6" value="6.5207" spread="1.73"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>DLX5 (2 week)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10.4258" spread=".038"/>
                    <measurement group_id="O2" value="12.2275" spread="1.08"/>
                    <measurement group_id="O3" value="5.9966" spread="1.56"/>
                    <measurement group_id="O4" value="6.1543" spread="1.75"/>
                    <measurement group_id="O5" value="9.4077" spread="1.09"/>
                    <measurement group_id="O6" value="9.4038" spread="1.12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>BMP1 (2 weeks)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.2225" spread="0.46"/>
                    <measurement group_id="O2" value="5.9042" spread="0.84"/>
                    <measurement group_id="O3" value="1.8624" spread="1.49"/>
                    <measurement group_id="O4" value="2.4895" spread="1.31"/>
                    <measurement group_id="O5" value="3.9986" spread="1.77"/>
                    <measurement group_id="O6" value="3.5056" spread="1.57"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>BGN (2 Weeks)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.6525" spread="0.63"/>
                    <measurement group_id="O2" value="3.0942" spread="1.25"/>
                    <measurement group_id="O3" value="-1.9201" spread="0.31"/>
                    <measurement group_id="O4" value="-0.6761" spread="0.22"/>
                    <measurement group_id="O5" value="0.9032" spread="1.86"/>
                    <measurement group_id="O6" value=".03906" spread="2.30"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>COL14A1 (2 weeks)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.9192" spread="0.52"/>
                    <measurement group_id="O2" value="4.4442" spread="0.33"/>
                    <measurement group_id="O3" value="0.5529" spread="0.42"/>
                    <measurement group_id="O4" value="0.9162" spread="0.66"/>
                    <measurement group_id="O5" value="2.4111" spread="1.31"/>
                    <measurement group_id="O6" value="3.0112" spread="1.18"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>CSF1 (2 weeks)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.2292" spread="0.51"/>
                    <measurement group_id="O2" value="6.4042" spread="0.23"/>
                    <measurement group_id="O3" value="0.8180" spread="0.95"/>
                    <measurement group_id="O4" value="2.1533" spread="0.81"/>
                    <measurement group_id="O5" value="4.5506" spread="1.39"/>
                    <measurement group_id="O6" value="4.6397" spread="1.21"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>GLI1 (4 weeks)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.7365" spread="0.27"/>
                    <measurement group_id="O2" value="8.2807" spread="0.23"/>
                    <measurement group_id="O3" value="4.8091" spread="0.33"/>
                    <measurement group_id="O4" value="4.7381" spread="1.41"/>
                    <measurement group_id="O5" value="8.7988" spread="3.77"/>
                    <measurement group_id="O6" value="9.1999" spread="2.04"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>IGF1R (4 weeks)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.5259" spread="0.31"/>
                    <measurement group_id="O2" value="3.8134" spread="1.08"/>
                    <measurement group_id="O3" value="2.6811" spread="1.08"/>
                    <measurement group_id="O4" value="3.0398" spread="0.30"/>
                    <measurement group_id="O5" value="5.6048" spread="2.31"/>
                    <measurement group_id="O6" value="6.3467" spread="0.65"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>PHEX (4 weeks)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.1578" spread="0.58"/>
                    <measurement group_id="O2" value="6.4186" spread="2.08"/>
                    <measurement group_id="O3" value="0.2916" spread="0.26"/>
                    <measurement group_id="O4" value="3.9890" spread="0.41"/>
                    <measurement group_id="O5" value="5.7960" spread="1.62"/>
                    <measurement group_id="O6" value="6.8678" spread="0.80"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>FGF1 (4 weeks)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.0907" spread="0.19"/>
                    <measurement group_id="O2" value="5.3543" spread="0.85"/>
                    <measurement group_id="O3" value="2.5977" spread="0.23"/>
                    <measurement group_id="O4" value="3.1967" spread="1.77"/>
                    <measurement group_id="O5" value="6.3124" spread="4.51"/>
                    <measurement group_id="O6" value="5.8513" spread="0.53"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>FGFR2 (4 weeks)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.5910" spread="0.38"/>
                    <measurement group_id="O2" value="3.8245" spread="1.98"/>
                    <measurement group_id="O3" value="0.8745" spread="0.10"/>
                    <measurement group_id="O4" value="2.9709" spread="0.34"/>
                    <measurement group_id="O5" value="4.3674" spread="2.19"/>
                    <measurement group_id="O6" value="5.4090" spread="0.71"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>TGFBR2 (4weeks)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.3029" spread="0.25"/>
                    <measurement group_id="O2" value="0.9102" spread="0.79"/>
                    <measurement group_id="O3" value="-0.9658" spread="1.74"/>
                    <measurement group_id="O4" value="-0.2509" spread="2.96"/>
                    <measurement group_id="O5" value="2.2868" spread="1.89"/>
                    <measurement group_id="O6" value="2.9935" spread="1.23"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>FGF2 (4 weeks)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.7981" spread="0.26"/>
                    <measurement group_id="O2" value="5.9102" spread="0.71"/>
                    <measurement group_id="O3" value="-0.9658" spread="1.33"/>
                    <measurement group_id="O4" value="4.2644" spread="1.97"/>
                    <measurement group_id="O5" value="6.8459" spread="3.20"/>
                    <measurement group_id="O6" value="7.7363" spread="1.34"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>FGFR1 (4 weeks)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.3229" spread="0.71"/>
                    <measurement group_id="O2" value="1.4584" spread="0.41"/>
                    <measurement group_id="O3" value="-0.5135" spread="0.20"/>
                    <measurement group_id="O4" value="-0.9003" spread="0.24"/>
                    <measurement group_id="O5" value="2.4234" spread="2.36"/>
                    <measurement group_id="O6" value="2.7818" spread="2.16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>IGF1 (4 weeks)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.5603" spread="1.09"/>
                    <measurement group_id="O2" value="3.3670" spread="1.25"/>
                    <measurement group_id="O3" value="2.1275" spread="2.47"/>
                    <measurement group_id="O4" value="1.8615" spread="0.40"/>
                    <measurement group_id="O5" value="4.2738" spread="1.55"/>
                    <measurement group_id="O6" value="5.4869" spread="1.68"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>BMP2 (4 weeks)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.0738" spread="1.26"/>
                    <measurement group_id="O2" value="4.3821" spread="0.50"/>
                    <measurement group_id="O3" value="3.3444" spread="1.30"/>
                    <measurement group_id="O4" value="3.6476" spread="0.94"/>
                    <measurement group_id="O5" value="7.1463" spread="2.56"/>
                    <measurement group_id="O6" value="6.5207" spread="0.91"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>BMP1 (4 weeks)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.6543" spread="0.43"/>
                    <measurement group_id="O2" value="2.2410" spread="0.59"/>
                    <measurement group_id="O3" value="0.6949" spread="0.14"/>
                    <measurement group_id="O4" value="1.0592" spread="0.20"/>
                    <measurement group_id="O5" value="3.9986" spread="2.71"/>
                    <measurement group_id="O6" value="1.5697" spread="1.63"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Group Based Differences (i.e. Healthy, Osteopenic and Diabetic) in Gene Expression Using Fold Changes Between Titanium and Trabecular at 4 Weeks.</title>
        <description>Findings from expression arrays will be used to perform quantitative PCR analyses using SAB Superarrays (SuperArray GEArray), to enable a quantitativeassay of mRNA levels of specific inflammatory and growth factor molecules</description>
        <time_frame>4 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Healthy Tantalum</title>
            <description>Subjects who are non-diabetic, with no history of smoking within the past two years and no metabolic bone disease diagnosis.&#xD;
Zimmer Metal Test Cylinder: For all subjects 2 titanium and 2 trabecular 2.9-3.0 mm x 5 mm test cylinders will be implanted in alveolar bone. One of each type will be removed at 2 weeks. The remaining two will be removed at 4 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Heathy Titanium</title>
            <description>Subjects who are non-diabetic, with no history of smoking within the past two years and no metabolic bone disease diagnosis.&#xD;
Zimmer Metal Test Cylinder: For all subjects 2 titanium and 2 trabecular 2.9-3.0 mm x 5 mm test cylinders will be implanted in alveolar bone. One of each type will be removed at 2 weeks. The remaining two will be removed at 4 weeks.</description>
          </group>
          <group group_id="O3">
            <title>Diabetic Tantalum</title>
            <description>Subjects must have Type 2 diabetes mellitus as diagnosed by a physician or in medication history. The condition must be currently diagnosed and treated by medications and/or insulin.&#xD;
Zimmer Metal Test Cylinder: For all subjects 2 titanium and 2 trabecular 2.9-3.0 mm x 5 mm test cylinders will be implanted in alveolar bone. One of each type will be removed at 2 weeks. The remaining two will be removed at 4 weeks</description>
          </group>
          <group group_id="O4">
            <title>Diabetic Titanium</title>
            <description>Subjects must have Type 2 diabetes mellitus as diagnosed by a physician or in medication history. The condition must be currently diagnosed and treated by medications and/or insulin.&#xD;
Zimmer Metal Test Cylinder: For all subjects 2 titanium and 2 trabecular 2.9-3.0 mm x 5 mm test cylinders will be implanted in alveolar bone. One of each type will be removed at 2 weeks. The remaining two will be removed at 4 weeks.</description>
          </group>
          <group group_id="O5">
            <title>Osteoporosis Tantalum</title>
            <description>Subjects must be diagnosed with osteoporosis or osteopenia and must be currently under the care of a physician and treatment with oral bisphosphonates&#xD;
Zimmer Metal Test Cylinder: For all subjects 2 titanium and 2 trabecular 2.9-3.0 mm x 5 mm test cylinders will be implanted in alveolar bone. One of each type will be removed at 2 weeks. The remaining two will be removed at 4 weeks.</description>
          </group>
          <group group_id="O6">
            <title>Osteoporosis Titanium</title>
            <description>Subjects must be diagnosed with osteoporosis or osteopenia and must be currently under the care of a physician and treatment with oral bisphosphonates&#xD;
Zimmer Metal Test Cylinder: For all subjects 2 titanium and 2 trabecular 2.9-3.0 mm x 5 mm test cylinders will be implanted in alveolar bone. One of each type will be removed at 2 weeks. The remaining two will be removed at 4 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Group Based Differences (i.e. Healthy, Osteopenic and Diabetic) in Gene Expression Using Fold Changes Between Titanium and Trabecular at 4 Weeks.</title>
          <description>Findings from expression arrays will be used to perform quantitative PCR analyses using SAB Superarrays (SuperArray GEArray), to enable a quantitativeassay of mRNA levels of specific inflammatory and growth factor molecules</description>
          <units>Fold Change</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="12"/>
                <count group_id="O2" value="12"/>
                <count group_id="O3" value="12"/>
                <count group_id="O4" value="12"/>
                <count group_id="O5" value="8"/>
                <count group_id="O6" value="8"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>PHEX</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.158" spread="0.58"/>
                    <measurement group_id="O2" value="6.419" spread="2.08"/>
                    <measurement group_id="O3" value="5.796" spread="1.62"/>
                    <measurement group_id="O4" value="6.868" spread="0.80"/>
                    <measurement group_id="O5" value="0.292" spread="0.26"/>
                    <measurement group_id="O6" value="3.989" spread="0.41"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>FGF1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="40.91" spread="0.19"/>
                    <measurement group_id="O2" value="5.3454" spread="0.85"/>
                    <measurement group_id="O3" value="6.312" spread="4.51"/>
                    <measurement group_id="O4" value="5.851" spread="0.53"/>
                    <measurement group_id="O5" value="2.598" spread="0.23"/>
                    <measurement group_id="O6" value="3.197" spread="1.77"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>FGFR2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.591" spread="0.38"/>
                    <measurement group_id="O2" value="3.824" spread="1.98"/>
                    <measurement group_id="O3" value="4.367" spread="2019"/>
                    <measurement group_id="O4" value="5.409" spread="0.71"/>
                    <measurement group_id="O5" value="0.875" spread="0.10"/>
                    <measurement group_id="O6" value="2.971" spread="0.34"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>TGFBR2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.303" spread="0.25"/>
                    <measurement group_id="O2" value="0.901" spread="0.79"/>
                    <measurement group_id="O3" value="2.287" spread="1.89"/>
                    <measurement group_id="O4" value="2.994" spread="1.23"/>
                    <measurement group_id="O5" value="-0.966" spread="1.74"/>
                    <measurement group_id="O6" value="-0.251" spread="2.96"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>FGF2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.79" spread="0.26"/>
                    <measurement group_id="O2" value="5.910" spread="0.71"/>
                    <measurement group_id="O3" value="6.846" spread="3.20"/>
                    <measurement group_id="O4" value="7.736" spread="1.34"/>
                    <measurement group_id="O5" value="-0.966" spread="1.33"/>
                    <measurement group_id="O6" value="4.264" spread="1.97"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>FGFR1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.323" spread="0.71"/>
                    <measurement group_id="O2" value="1.458" spread="0.41"/>
                    <measurement group_id="O3" value="2.423" spread="2.36"/>
                    <measurement group_id="O4" value="2.782" spread="2.16"/>
                    <measurement group_id="O5" value="-0.513" spread="0.20"/>
                    <measurement group_id="O6" value="-0.9" spread="0.24"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>IGF1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.56" spread="1.09"/>
                    <measurement group_id="O2" value="3.367" spread="1.25"/>
                    <measurement group_id="O3" value="4.2474" spread="1.55"/>
                    <measurement group_id="O4" value="5.487" spread="1.68"/>
                    <measurement group_id="O5" value="2.128" spread="2.47"/>
                    <measurement group_id="O6" value="1.861" spread="0.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>BMP2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.074" spread="1.26"/>
                    <measurement group_id="O2" value="4.382" spread="0.5"/>
                    <measurement group_id="O3" value="7.146" spread="2.56"/>
                    <measurement group_id="O4" value="6.521" spread="0.91"/>
                    <measurement group_id="O5" value="3.344" spread="1.30"/>
                    <measurement group_id="O6" value="3.648" spread="0.94"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>BMP1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.654" spread="0.43"/>
                    <measurement group_id="O2" value="2.241" spread="0.59"/>
                    <measurement group_id="O3" value="3.999" spread="2.71"/>
                    <measurement group_id="O4" value="1.570" spread="1.63"/>
                    <measurement group_id="O5" value="0.695" spread="0.14"/>
                    <measurement group_id="O6" value="1.059" spread="0.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>CSF1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.229" spread="0.51"/>
                    <measurement group_id="O2" value="6.404" spread="0.23"/>
                    <measurement group_id="O3" value="4.551" spread="1.39"/>
                    <measurement group_id="O4" value="4.64" spread="1.21"/>
                    <measurement group_id="O5" value="0.818" spread="0.95"/>
                    <measurement group_id="O6" value="2.153" spread="0.81"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>GLI1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.736" spread="0.27"/>
                    <measurement group_id="O2" value="8.281" spread="0.23"/>
                    <measurement group_id="O3" value="8.799" spread="3.77"/>
                    <measurement group_id="O4" value="9.2" spread="2.04"/>
                    <measurement group_id="O5" value="4.809" spread="0.33"/>
                    <measurement group_id="O6" value="4.738" spread="1.41"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>IGF1R</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.526" spread="0.31"/>
                    <measurement group_id="O2" value="3.813" spread="1.08"/>
                    <measurement group_id="O3" value="5.605" spread="2.31"/>
                    <measurement group_id="O4" value="6.347" spread="0.65"/>
                    <measurement group_id="O5" value="2.681" spread="1.08"/>
                    <measurement group_id="O6" value="3.04" spread="0.30"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>2 years, 4 months</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Healthy Volunteers</title>
          <description>Subjects who are non-diabetic, with no history of smoking within the past two years and no metabolic bone disease diagnosis.&#xD;
Zimmer Trabecular Metal Test Cylinder: For all subjects 2 titanium and 2 trabecular 2.9-3.0 mm x 5 mm test cylinders will be implanted in alveolar bone. One of each type will be removed at 2 weeks. The remaining two will be removed at 4 weeks.&#xD;
Zimmer Titanium Test Cylinder: For all subjects 2 titanium and 2 trabecular 2.9-3.0 mm x 5 mm test cylinders will be implanted in alveolar bone. One of each type will be removed at 2 weeks. The remaining two will be removed at 4 weeks.</description>
        </group>
        <group group_id="E2">
          <title>Diabetic Subjects</title>
          <description>Subjects must have Type 2 diabetes mellitus as diagnosed by a physician or in medication history. The condition must be currently diagnosed and treated by medications and/or insulin.&#xD;
Zimmer Trabecular Metal Test Cylinder: For all subjects 2 titanium and 2 trabecular 2.9-3.0 mm x 5 mm test cylinders will be implanted in alveolar bone. One of each type will be removed at 2 weeks. The remaining two will be removed at 4 weeks.&#xD;
Zimmer Titanium Test Cylinder: For all subjects 2 titanium and 2 trabecular 2.9-3.0 mm x 5 mm test cylinders will be implanted in alveolar bone. One of each type will be removed at 2 weeks. The remaining two will be removed at 4 weeks.</description>
        </group>
        <group group_id="E3">
          <title>Osteopenic Subjects</title>
          <description>Subjects must be diagnosed with osteoporosis or osteopenia and must be currently under the care of a physician and treatment with oral bisphosphonates&#xD;
Zimmer Trabecular Metal Test Cylinder: For all subjects 2 titanium and 2 trabecular 2.9-3.0 mm x 5 mm test cylinders will be implanted in alveolar bone. One of each type will be removed at 2 weeks. The remaining two will be removed at 4 weeks.&#xD;
Zimmer Titanium Test Cylinder: For all subjects 2 titanium and 2 trabecular 2.9-3.0 mm x 5 mm test cylinders will be implanted in alveolar bone. One of each type will be removed at 2 weeks. The remaining two will be removed at 4 weeks.</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Delayed healing response</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Gingival Swelling &amp; Pain</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="12"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Steven Offenbacher, DDS, PhD, MMSc</name_or_title>
      <organization>UNC School of Dentistry</organization>
      <phone>919-537-3205</phone>
      <email>steven_offenbacher@unc.edu</email>
    </point_of_contact>
  </clinical_results>
</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/NCT01714024
org study id: ZMU 11-2539
nct id: NCT01714024
lead sponsor: 
collaborator: 
has dmc: Yes
The purpose of this research study is to compare the healing differences of two metals
      (trabecular vs. standard titanium) that are used for dental implants. In addition;
      investigators will be examine these differences in the gene expression profiles in subjects
      with three conditions associated with delayed healing: diabetes and osteoporosis.

      The study will last at least 11 weeks consisting of 6 appointments. All visits will be
      carried out at the GO Health Center within the UNC School of Dentistry. Visits will last
      between 30 minutes to 3 hours depending on the particular visit.

      The visits will consist of: Obtaining consent, doing a health history, measuring vital signs,
      doing dental exams of the teeth and gums, collecting samples of saliva dental radiographs
      (X-rays), a teeth cleaning, having 4 temporary mini test cylinders placed in areas of the
      lower jaw where teeth are missing and implant surgery to place up to four permanent implants.
The plan is to recruit subjects into 3 groups: 1) systemically healthy, 2) subjects with
      diabetes (ADA classification determined by glycosylated hemoglobin A1C levels), and 3)
      subjects with osteoporosis (limited to those on either no drugs or oral bisphosphonates
      only). All subjects recruited will have already been approved and treatment planned for
      implant placement by non-study personnel to avoid any potential conflict of interest. All
      subjects will have mandibular radiographs that show edentulous ridge areas that provide
      enough alveolar ridge space to place two test cylinders (each approximately 2.9-3 x 5mm) on
      each side of the mandible. One side will have two titanium test cylinders and the
      contralateral side will have two trabecular metal test cylinders. After placement of these 4
      test cylinders, one will be removed contra laterally from each side at weeks 2 and 4 of
      healing. Thus, by 28 days all test cylinders will be removed.

      It has been our experience that each cylinder after removal will contain enough cells to
      provide approximately 10-20μg of total RNA. This quantity of total RNA is sufficient to run
      an Affymetrix chip and have enough mRNA for PCR confirmation. Sampling at 3 days after
      placement is too soon, as it does not provide adequate mRNA for the analysis, since the clot
      has not become remodeled or adequately organized to be cellular. Thus, by 1 week organization
      of the osseous healing will have begun and at week 2 it will be beginning to mature. The week
      2 sampling time point) will provide us with early molecular kinetics of the healing response
      to compare the two metal surfaces and the differences in gene expression that may be
      associated with diabetes and osteoporosis. At weeks 2 and 4 the test cylinders will be
      removed using a 5.0 mm diameter tissue punch and a 5 mm trephine drill. Investigators will
      select 18 random patients (6 subjects per group) to provide (two test cylinders for each, 36
      samples) for histology. Investigators will use the trephine drill to remove the 4 week test
      cylinders in all 3 groups of subjects. In all cases, a subject is eligible for this study by
      being pretreatment planned to receive a permanent implant bilaterally, which will be placed
      at donor sites. According to the participant's individual treatment plan, after test
      cylinders are removed, each site will receive an implant using either a standard 4.1 or 4.7
      mm tapered screw vent design implant. The removed test cylinders will be briefly rinsed in
      saline and prepared chair side for either mRNA extraction or for histology.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: Fold Change in Gene Expression Comparing Trabecular Metal to Standard Titanium.
time frame: 2 weeks & 4 weeks post placement
description: Samples were analyzed comparing the osteogenic potential associated with titanium and porous tantalum dental implants (cylinders) at 2 and 4 weeks using transcriptome analyses. The primary outcome data are displayed showing the Average Delta ∆ (Ct) for osteogenic genes relative to the housekeeping markers. The numerical value of the CT is inversely related to the amount of amplicon in the reaction (i.e., the lower the CT, the greater the amount of amplicon).
measure: Group Based Differences (i.e. Healthy, Osteopenic and Diabetic) in Gene Expression Using Fold Changes Between Titanium and Trabecular at 4 Weeks.
time frame: 4 weeks
description: Findings from expression arrays will be used to perform quantitative PCR analyses using SAB Superarrays (SuperArray GEArray), to enable a quantitativeassay of mRNA levels of specific inflammatory and growth factor molecules
arm group label: Healthy Volunteers
arm group type: Experimental
description: Subjects who are non-diabetic, with no history of smoking within the past two years and no metabolic bone disease diagnosis.
arm group label: Diabetic Subjects
arm group type: Experimental
description: Subjects must have Type 2 diabetes mellitus as diagnosed by a physician or in medication history. The condition must be currently diagnosed and treated by medications and/or insulin.
arm group label: Osteopenic Subjects
arm group type: Experimental
description: Subjects must be diagnosed with osteoporosis or osteopenia and must be currently under the care of a physician and treatment with oral bisphosphonates
intervention type: Device
intervention name: Zimmer Trabecular Metal Test Cylinder
description: For all subjects 2 titanium and 2 trabecular 2.9-3.0 mm x 5 mm test cylinders will be implanted in alveolar bone. One of each type will be removed at 2 weeks. The remaining two will be removed at 4 weeks.
arm group label: Diabetic Subjects
arm group label: Healthy Volunteers
arm group label: Osteopenic Subjects
intervention type: Device
intervention name: Zimmer Titanium Test Cylinder
description: For all subjects 2 titanium and 2 trabecular 2.9-3.0 mm x 5 mm test cylinders will be implanted in alveolar bone. One of each type will be removed at 2 weeks. The remaining two will be removed at 4 weeks.
arm group label: Diabetic Subjects
arm group label: Healthy Volunteers
arm group label: Osteopenic Subjects
criteria: 
gender: All
minimum age: 21 Years
maximum age: 80 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Steven Offenbacher, DDS, PhD, MMSc
role: Principal Investigator
affiliation: University of North Carolina School of Dentistry
facility: 
country: United States
url: http://gohealthcenter.org/
description: This website is affiliated with the UNC School of Dentistry and is primarily used to inform potential participants about research being done within the General and Oral Health Center.
responsible party type: Sponsor
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 