<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/NCT03836378</url>
  </required_header>
  <id_info>
    <org_study_id>18-2447</org_study_id>
    <nct_id>NCT03836378</nct_id>
  </id_info>
  <brief_title>Addition of Dehydrated Human Amnion-Chorion Membrane During Scaling and Root Planing</brief_title>
  <official_title>Innovative Addition of Dehydrated Human Amnion-Chorion Membrane During Scaling and Root Planing</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Colorado, Denver</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Colorado, Denver</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Hypothesis: There will be an additional reduction of pocket depth and gain of clinical&#xD;
      attachment when dehydrated human amnion-chorion membrane (dHACM) is placed into the&#xD;
      periodontal disease defect after mechanical scaling and root planing.&#xD;
&#xD;
      Specific Aim 1: to compare the clinical and radiographical outcome of using dehydrated human&#xD;
      amnion-chorion membrane (dHACM) (commercially available as BioXclude®) with mechanical&#xD;
      scaling and root planing.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The study product BioXclude™ is an Amnion-Chorion allograft membrane, a new membrane made&#xD;
      from human amniotic tissue donated from elective Caesarean section births. Amniotic sacs have&#xD;
      been used since the early 1900's to promote skin wound healing. All donated tissue has been&#xD;
      carefully screened and tested to reduce the risk of transmitting disease. BioXclude™ is&#xD;
      commercially available as a dental wound covering, for bone reconstruction procedures, and as&#xD;
      a treatment for receding gums, and the manufacturer has met all federal requirements for&#xD;
      distributing this product. However, the use of the membrane for this research treatment of&#xD;
      periodontal disease is investigational. BioXclude™ does not meet the criteria for FDA&#xD;
      oversight as a drug, device or biologic and is regulated as a Human Cells, Tissues, and&#xD;
      Cellular and Tissue based product. The product is designed for use as wound covering in a&#xD;
      variety of dental applications.&#xD;
&#xD;
      Quadrants (right/left, upper/lower) of the mouth will randomly be assigned by block&#xD;
      randomization via flip of a coin with either 1) scaling and root planing alone, or 2) scaling&#xD;
      and root planing with 8 x 8mm Dehydrated Human Amnion/Chorion Membrane (dHACM) placement&#xD;
      within the periodontal pocket at &gt;5mm sites. The participant will act as their own control.&#xD;
      There will be one side of the mouth that will receive the dHACM intervention with scaling and&#xD;
      root planning, and one side that will be the control (scaling and root planning only).&#xD;
      Depending on the extent of the disease (&gt;5mm probing depths) the intervention may involve&#xD;
      upper and lower jaws on that side of the mouth or only one jaw per side (1-2&#xD;
      interventions/1-2 controls per mouth). The addition of dHACM will be a one-time placement.&#xD;
&#xD;
      The only research-related procedures that will differ from standard of care are standardizing&#xD;
      the x-rays (with custom bite block), placement of the dehydrated human amnion-chorion&#xD;
      membrane (dHACM), supra-gingival cleaning at 3 and 6 months (instead of supra- and&#xD;
      sub-gingival) and x-rays taken at 9 months.&#xD;
&#xD;
      The two examiners (board certified periodontists) completing the periodontal examination will&#xD;
      be blinded to the treatment allocated to the participant by the clinical provider (graduate&#xD;
      periodontal resident or hygienist). Clinical measurements which are standard of care of a&#xD;
      periodontal examination will include: probing depth, bleeding on probing, clinical attachment&#xD;
      level, mobility, and plaque index (Sillness and Loe index). Probing measurements will be made&#xD;
      at 6 location points on all teeth in the dentition using a calibrated University of North&#xD;
      Carolina (UNC) periodontal probe with readings made to the nearest millimeter. Clinical&#xD;
      attachment levels will be made from the cemento-enamel junction or nearest landmark. All&#xD;
      sites with probing depths measuring &gt;4mm will be measured a second time, and the average of&#xD;
      the 2 readings will be used as the site-specific probing depth endpoint. Concomitant&#xD;
      medications and safety evaluation will be recorded at each visit. Any suspected adverse&#xD;
      events or allergic responses will be evaluated by the investigator.&#xD;
&#xD;
      Clinical measurements will be made at the following time points: baseline; Month 1; Month 3;&#xD;
      Month 6; Month 9. Four bitewing radiographs will be taken for evaluation with custom bite&#xD;
      mounting utilizing a long cone paralleling technique and will be made at: baseline; Month 9.&#xD;
      Baseline x-rays are the standard of care for a periodontal examination. Standardizing the&#xD;
      x-rays with a custom bite block and re-taking the x-rays at 9 months are for research-related&#xD;
      procedures. Participants will be instructed not to perform interproximal oral hygiene for 7&#xD;
      days following treatment. At the 1, 3, 6 and 9 month follow up visits, Participants will be&#xD;
      instructed on the Bass brushing technique as well as the proper use of dental floss as is&#xD;
      standard of care for oral hygiene instructions. At the 3 and 6-month visits, supra-gingival&#xD;
      plaque removal will be performed. At the completion of the study (9 months) supra- and&#xD;
      sub-gingival scaling will be performed as indicated for each participant. Plaque removal is&#xD;
      the standard of care for maintaining a periodontally diseased participant. For research due&#xD;
      to the placement of the membrane, sub-gingival cleaning will be avoided at 3 and 6 months and&#xD;
      the cleaning will be supra-gingival only. This differs from the standard of care, which would&#xD;
      have sub- and supra-gingival cleaning at 3 and 6 months. Cleaning will return to standard of&#xD;
      care at 9 months, where participants will have sub- and supra-gingival cleaning.&#xD;
&#xD;
      To summarize, the standard of care will be followed for the initial x-rays, clinical&#xD;
      measurements, scaling and root planing, 1 month re-evaluation, 3, 6 and 9 month cleaning&#xD;
      visits. For the standard of care non-standardized x-rays are normally used. For research&#xD;
      purposes, the investigators will be standardizing the x-rays with a custom bite block and&#xD;
      re-taking x-rays at 9 months. In addition for research purposes we will be placing the&#xD;
      dehydrated human amnion-chorion membrane (dHACM), and having supra-gingival cleanings at 3&#xD;
      and 6 months (instead of supra- and sub-gingival).&#xD;
&#xD;
      Three examiners (board certified periodontists) will be calibrated to each other for the&#xD;
      collection of the data and interexaminer reliability will be calculated. The three examiners&#xD;
      will be calibrated for probing depth and clinical attachment levels by reproducing clinical&#xD;
      measurements on a single participant until the measurements are consistently within 0.5 and&#xD;
      the percentage is 95 percent agreement&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">January 1, 2020</start_date>
  <completion_date type="Anticipated">September 1, 2023</completion_date>
  <primary_completion_date type="Anticipated">September 1, 2023</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>Single Group Assignment</intervention_model>
    <intervention_model_description>The participant will have half the mouth completed with scaling and root planing alone and half the mouth completed with scaling and root planing with the addition of membrane in deep probing depth sites.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Investigator, Outcomes Assessor)</masking>
    <masking_description>A random allocation will be completed (flip of coin) which side will receive the membrane placement. The care provider (hygienist) will be aware of the membrane placement. The investigator and outcome assessor (periodontist) will not know which sites received the membrane placement.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Pocket Depths</measure>
    <time_frame>9 months</time_frame>
    <description>Mean change in probing depths (using a UNC probe to measure probing depths).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Attachment Levels</measure>
    <time_frame>9 months</time_frame>
    <description>Mean change in attachment level (using a UNC probe to measure attachment levels).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Bone Gain</measure>
    <time_frame>9 months</time_frame>
    <description>Radiographic comparison from baseline radiograph to Month 9.</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">250</enrollment>
  <condition>Periodontal Diseases</condition>
  <arm_group>
    <arm_group_label>Deep Cleaning and Intervention</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>One side of the participant's mouth will receive a deep cleaning in addition to the placement of a BioXclude™ membrane in the deep pocket sites. The participant will then be followed for 9 months with routine care.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Deep Cleaning Only</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>One side of the participant's mouth will receive deep cleaning (scaling and root planning) only. The participant will then be followed for 9 months with routine care.</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>BioXclude™</intervention_name>
    <description>The addition of BioXclude™ dehydrated human amnion-chorion membrane into deep pockets with scaling and root planing.</description>
    <arm_group_label>Deep Cleaning and Intervention</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Stage III and IV periodontitis (generalized moderate to severe chronic periodontitis)&#xD;
&#xD;
          -  At least 4 teeth (to include at least one qualifying tooth on the right and left side&#xD;
             of the mouth) with probing depths of 6 to 9 millimeters and bleeding on probing&#xD;
&#xD;
          -  at least 18 years of age&#xD;
&#xD;
          -  consent to be in the study&#xD;
&#xD;
          -  non-emergent dental treatment&#xD;
&#xD;
          -  American Society of Anesthesiologists (ASA) Class I or II (prticipants that are&#xD;
             systemically healthy or have a systemic condition that is well controlled and are able&#xD;
             to receive elective dental care)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  &lt;18 years old or &gt;100 years old&#xD;
&#xD;
          -  currently pregnant or within 6 months postpartum, nursing&#xD;
&#xD;
          -  require antibiotic prophylaxis prior to dental procedures as outlined by the 2017&#xD;
             American Heart Association guidelines&#xD;
&#xD;
          -  decisionally challenged adults&#xD;
&#xD;
          -  ASA Class III or IV (patients that have non-controlled systemic conditions that are&#xD;
             unable to have elective dental care)&#xD;
&#xD;
          -  had periodontal therapy within 6 months of baseline treatment visit&#xD;
&#xD;
          -  antibiotic therapy within 3 months prior to enrollment&#xD;
&#xD;
          -  chronic therapy within 1 month prior to enrollment with medications that could affect&#xD;
             periodontal status or healing&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>100 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Sangeetha Chandrasekaran</name>
      <address>
        <city>Aurora</city>
        <state>Colorado</state>
        <zip>80045</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>February 2023</verification_date>
  <study_first_submitted>February 7, 2019</study_first_submitted>
  <study_first_submitted_qc>February 7, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 11, 2019</study_first_posted>
  <last_update_submitted>February 27, 2023</last_update_submitted>
  <last_update_submitted_qc>February 27, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">March 1, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Periodontal Diseases</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/NCT03836378
org study id: 18-2447
nct id: NCT03836378
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Hypothesis: There will be an additional reduction of pocket depth and gain of clinical
      attachment when dehydrated human amnion-chorion membrane (dHACM) is placed into the
      periodontal disease defect after mechanical scaling and root planing.

      Specific Aim 1: to compare the clinical and radiographical outcome of using dehydrated human
      amnion-chorion membrane (dHACM) (commercially available as BioXclude®) with mechanical
      scaling and root planing.
The study product BioXclude™ is an Amnion-Chorion allograft membrane, a new membrane made
      from human amniotic tissue donated from elective Caesarean section births. Amniotic sacs have
      been used since the early 1900's to promote skin wound healing. All donated tissue has been
      carefully screened and tested to reduce the risk of transmitting disease. BioXclude™ is
      commercially available as a dental wound covering, for bone reconstruction procedures, and as
      a treatment for receding gums, and the manufacturer has met all federal requirements for
      distributing this product. However, the use of the membrane for this research treatment of
      periodontal disease is investigational. BioXclude™ does not meet the criteria for FDA
      oversight as a drug, device or biologic and is regulated as a Human Cells, Tissues, and
      Cellular and Tissue based product. The product is designed for use as wound covering in a
      variety of dental applications.

      Quadrants (right/left, upper/lower) of the mouth will randomly be assigned by block
      randomization via flip of a coin with either 1) scaling and root planing alone, or 2) scaling
      and root planing with 8 x 8mm Dehydrated Human Amnion/Chorion Membrane (dHACM) placement
      within the periodontal pocket at >5mm sites. The participant will act as their own control.
      There will be one side of the mouth that will receive the dHACM intervention with scaling and
      root planning, and one side that will be the control (scaling and root planning only).
      Depending on the extent of the disease (>5mm probing depths) the intervention may involve
      upper and lower jaws on that side of the mouth or only one jaw per side (1-2
      interventions/1-2 controls per mouth). The addition of dHACM will be a one-time placement.

      The only research-related procedures that will differ from standard of care are standardizing
      the x-rays (with custom bite block), placement of the dehydrated human amnion-chorion
      membrane (dHACM), supra-gingival cleaning at 3 and 6 months (instead of supra- and
      sub-gingival) and x-rays taken at 9 months.

      The two examiners (board certified periodontists) completing the periodontal examination will
      be blinded to the treatment allocated to the participant by the clinical provider (graduate
      periodontal resident or hygienist). Clinical measurements which are standard of care of a
      periodontal examination will include: probing depth, bleeding on probing, clinical attachment
      level, mobility, and plaque index (Sillness and Loe index). Probing measurements will be made
      at 6 location points on all teeth in the dentition using a calibrated University of North
      Carolina (UNC) periodontal probe with readings made to the nearest millimeter. Clinical
      attachment levels will be made from the cemento-enamel junction or nearest landmark. All
      sites with probing depths measuring >4mm will be measured a second time, and the average of
      the 2 readings will be used as the site-specific probing depth endpoint. Concomitant
      medications and safety evaluation will be recorded at each visit. Any suspected adverse
      events or allergic responses will be evaluated by the investigator.

      Clinical measurements will be made at the following time points: baseline; Month 1; Month 3;
      Month 6; Month 9. Four bitewing radiographs will be taken for evaluation with custom bite
      mounting utilizing a long cone paralleling technique and will be made at: baseline; Month 9.
      Baseline x-rays are the standard of care for a periodontal examination. Standardizing the
      x-rays with a custom bite block and re-taking the x-rays at 9 months are for research-related
      procedures. Participants will be instructed not to perform interproximal oral hygiene for 7
      days following treatment. At the 1, 3, 6 and 9 month follow up visits, Participants will be
      instructed on the Bass brushing technique as well as the proper use of dental floss as is
      standard of care for oral hygiene instructions. At the 3 and 6-month visits, supra-gingival
      plaque removal will be performed. At the completion of the study (9 months) supra- and
      sub-gingival scaling will be performed as indicated for each participant. Plaque removal is
      the standard of care for maintaining a periodontally diseased participant. For research due
      to the placement of the membrane, sub-gingival cleaning will be avoided at 3 and 6 months and
      the cleaning will be supra-gingival only. This differs from the standard of care, which would
      have sub- and supra-gingival cleaning at 3 and 6 months. Cleaning will return to standard of
      care at 9 months, where participants will have sub- and supra-gingival cleaning.

      To summarize, the standard of care will be followed for the initial x-rays, clinical
      measurements, scaling and root planing, 1 month re-evaluation, 3, 6 and 9 month cleaning
      visits. For the standard of care non-standardized x-rays are normally used. For research
      purposes, the investigators will be standardizing the x-rays with a custom bite block and
      re-taking x-rays at 9 months. In addition for research purposes we will be placing the
      dehydrated human amnion-chorion membrane (dHACM), and having supra-gingival cleanings at 3
      and 6 months (instead of supra- and sub-gingival).

      Three examiners (board certified periodontists) will be calibrated to each other for the
      collection of the data and interexaminer reliability will be calculated. The three examiners
      will be calibrated for probing depth and clinical attachment levels by reproducing clinical
      measurements on a single participant until the measurements are consistently within 0.5 and
      the percentage is 95 percent agreement
allocation: Randomized
intervention model: Single Group Assignment
intervention model description: The participant will have half the mouth completed with scaling and root planing alone and half the mouth completed with scaling and root planing with the addition of membrane in deep probing depth sites.
primary purpose: Treatment
masking: Double (Investigator, Outcomes Assessor)
masking description: A random allocation will be completed (flip of coin) which side will receive the membrane placement. The care provider (hygienist) will be aware of the membrane placement. The investigator and outcome assessor (periodontist) will not know which sites received the membrane placement.
measure: Pocket Depths
time frame: 9 months
description: Mean change in probing depths (using a UNC probe to measure probing depths).
measure: Attachment Levels
time frame: 9 months
description: Mean change in attachment level (using a UNC probe to measure attachment levels).
measure: Bone Gain
time frame: 9 months
description: Radiographic comparison from baseline radiograph to Month 9.
arm group label: Deep Cleaning and Intervention
arm group type: Experimental
description: One side of the participant's mouth will receive a deep cleaning in addition to the placement of a BioXclude™ membrane in the deep pocket sites. The participant will then be followed for 9 months with routine care.
arm group label: Deep Cleaning Only
arm group type: No Intervention
description: One side of the participant's mouth will receive deep cleaning (scaling and root planning) only. The participant will then be followed for 9 months with routine care.
intervention type: Procedure
intervention name: BioXclude™
description: The addition of BioXclude™ dehydrated human amnion-chorion membrane into deep pockets with scaling and root planing.
arm group label: Deep Cleaning and Intervention
criteria: 
gender: All
minimum age: 18 Years
maximum age: 100 Years
healthy volunteers: Accepts Healthy Volunteers
facility: 
country: United States
responsible party type: Sponsor
mesh term: Periodontal Diseases
sharing ipd: No