<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/NCT02985645</url>
  </required_header>
  <id_info>
    <org_study_id>0153-16-NHR</org_study_id>
    <nct_id>NCT02985645</nct_id>
  </id_info>
  <brief_title>Graftless Maxillary Sinus Augmentation With CGF Utilizing DIVA System</brief_title>
  <official_title>Graftless Maxillary Sinus Augmentation With CGF Utilizing DIVA System</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Western Galilee Hospital-Nahariya</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Western Galilee Hospital-Nahariya</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study is intended to evaluate the efficiency of graftless maxillary sinus augmentation&#xD;
      with concentrated growth factor (CGF) utilizing &quot;dynamic implant valve approach&quot; (DIVA)&#xD;
      system.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Crestal bone deficiency in the posterior maxilla may present a therapeutic challenge when&#xD;
      dental implants are required. Sufficient bone volume is necessary for the long term survival&#xD;
      of the implant .&#xD;
&#xD;
      The two most used surgical techniques are the crestal and the lateral window. The latter was&#xD;
      first described by Tatum and subsequently, Boyene and James in 1980 . In the original&#xD;
      technique, after fracturing the sinus floor, an implant was placed and submerged during the&#xD;
      healing phase. The crestal osteotome technique is less invasive and was first described by&#xD;
      Summers in 1994 . In this technique, a set of osteotomes is used to prepare the implant site,&#xD;
      thereby allowing bone preservation.&#xD;
&#xD;
      Since the sinus augmentation was describes, bone grafts have been the mainstay of treatment.&#xD;
      Variable bone grafts, such as autografts, allografts, xenografts, alloplasts, or combinations&#xD;
      of different graft materials, have been used widely with similar results . Nonetheless,&#xD;
      successful bone augmentation in the maxillary sinus, without bone grafting, have been&#xD;
      reported in human and animal studies.&#xD;
&#xD;
      In 2011, Dong-Seok et al described sinus augmentation through a lateral window approach,&#xD;
      using a fibrin rich block with concentrated growth factor (CGF). The researchers showed&#xD;
      successful new bone formation in the sinus, with a success rate of 98% and no major&#xD;
      complications .&#xD;
&#xD;
      Graftless Sinus augmentation relies on bioactive mediators that stimulate cell proliferation,&#xD;
      matrix remodeling, and angiogenesis. CGF is one of the latest developments in this field, and&#xD;
      is produced by processing blood samples with a special centrifuge device. It contains several&#xD;
      mediators - platelet-derived growth factor (PDGF), transforming growth factor-b1 (TGF-b1) and&#xD;
      b2 (TGF-b2), fibroblast growth factor (FGF), vascular endothelial growth factor (VEGF), and&#xD;
      insulin-like growth factor (IGF). Because CGF is a dense fibrin matrix, richer in growth&#xD;
      factors than other preparations, it has proved to have a better regenerative capacity and&#xD;
      versatility .&#xD;
&#xD;
      As for the application of CGF, the introduction of the &quot;dynamic implant valve approach&quot;&#xD;
      (DIVA), a minimally invasive approach procedure, enables the use of a closed bone&#xD;
      augmentation technique. The implant was designed with an internal sealing screw that might&#xD;
      serve as drug delivery system via its channel.&#xD;
&#xD;
      In this study, a graftless maxillary sinus augmentation with CGF will be performed utilizing&#xD;
      DIVA system, and the bone formation will be periodically measured using panoramic X-ray and&#xD;
      cone beam computerized tomography (CBCT).&#xD;
&#xD;
      In addition, in vitro cumulative release of selected growth factors of the CGF will be&#xD;
      analyzed. The total quantity of growth factors will be checked using ELISA kits.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date>December 2016</start_date>
  <completion_date type="Anticipated">January 2018</completion_date>
  <primary_completion_date type="Anticipated">December 2017</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>bone formation after sinus augmentation</measure>
    <time_frame>one year</time_frame>
    <description>during postoperative follow-up, bone formation in the maxillary sinus will be assessed by periodic imaging.&#xD;
after one year the investigators expect to see complete implant integration into the bone formed in the maxillary sinus(e.g; the dental implant is completely covered by bone).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Quantification of growth factors released from the CGF matrix in vitro</measure>
    <time_frame>one year</time_frame>
    <description>ELISA test will be used to quantify the released growth factors, and the data will be compared to the factors released from regular bone material.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">20</enrollment>
  <condition>Alveolar Bone Loss</condition>
  <arm_group>
    <arm_group_label>Treatment</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>maxillary sinus augmentation with CGF</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>maxillary sinus augmentation with CGF</intervention_name>
    <description>Graftless maxillary sinus augmentation surgery with CGF application utilizing DIVA system</description>
    <arm_group_label>Treatment</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>&quot;dynamic implant valve approach&quot; - DIVA system</intervention_name>
    <description>The DIVA system will be used to apply the CGF to the maxillary sinus.</description>
    <arm_group_label>Treatment</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  No medical history of diseases involving bone metabolism&#xD;
&#xD;
          -  Patients that are treated by a prostodontist&#xD;
&#xD;
          -  Healthy oral cavity and sinuses, and good oral hygiene&#xD;
&#xD;
          -  No bone pathology demonstrated by X-ray&#xD;
&#xD;
          -  Residual sub-antral bone of at least 4mm as demonstrated by computerized tomography&#xD;
             (CT)&#xD;
&#xD;
          -  The patient does not participate in another clinical study&#xD;
&#xD;
          -  The patient can read and understand the informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Medical history of a disease affecting bone metabolism (Diabetes Mellitus, heart&#xD;
             disease, renal failure, osteoporosis)&#xD;
&#xD;
          -  Medical treatment that can affect bone metabolism (such as Bisphosphonates)&#xD;
&#xD;
          -  Patients treated with anticoagulants (such as Coumadin, Pradaxa)&#xD;
&#xD;
          -  Personal history of chemotherapy or radiotherapy&#xD;
&#xD;
          -  Patients with maxillary sinus pathology&#xD;
&#xD;
          -  Patients lacking a prostodontic treatment plan&#xD;
&#xD;
          -  Pregnant women&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Samer Srouji, Prof.</last_name>
    <role>Study Director</role>
    <affiliation>Western Galilee Medical Center</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Ruth Angel-Dar, Dr.</last_name>
    <phone>+972-4-9107076</phone>
    <email>rutiangel123@gmail.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Samer Srouji, Prof.</last_name>
    <phone>+972-4-9107270</phone>
    <email>dr.samersrouji@gmail.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Western Galilee Medical Center</name>
      <address>
        <city>Nahariya</city>
        <country>Israel</country>
      </address>
    </facility>
    <contact>
      <last_name>Sigal Shor</last_name>
      <phone>+972-4-9107270</phone>
      <email>sigal.shor@naharia.health.gov.il</email>
    </contact>
  </location>
  <location_countries>
    <country>Israel</country>
  </location_countries>
  <reference>
    <citation>Del Fabbro M, Corbella S, Weinstein T, Ceresoli V, Taschieri S. Implant survival rates after osteotome-mediated maxillary sinus augmentation: a systematic review. Clin Implant Dent Relat Res. 2012 May;14 Suppl 1:e159-68. doi: 10.1111/j.1708-8208.2011.00399.x. Epub 2011 Nov 14.</citation>
    <PMID>22082056</PMID>
  </reference>
  <reference>
    <citation>Tatum H Jr. Maxillary and sinus implant reconstructions. Dent Clin North Am. 1986 Apr;30(2):207-29.</citation>
    <PMID>3516738</PMID>
  </reference>
  <reference>
    <citation>Summers RB. The osteotome technique: Part 3--Less invasive methods of elevating the sinus floor. Compendium. 1994 Jun;15(6):698, 700, 702-4 passim; quiz 710.</citation>
    <PMID>7994726</PMID>
  </reference>
  <reference>
    <citation>Danesh-Sani SA, Loomer PM, Wallace SS. A comprehensive clinical review of maxillary sinus floor elevation: anatomy, techniques, biomaterials and complications. Br J Oral Maxillofac Surg. 2016 Sep;54(7):724-30. doi: 10.1016/j.bjoms.2016.05.008. Epub 2016 May 25.</citation>
    <PMID>27235382</PMID>
  </reference>
  <reference>
    <citation>Falah M, Sohn DS, Srouji S. Graftless sinus augmentation with simultaneous dental implant placement: clinical results and biological perspectives. Int J Oral Maxillofac Surg. 2016 Sep;45(9):1147-53. doi: 10.1016/j.ijom.2016.05.006. Epub 2016 May 31.</citation>
    <PMID>27256011</PMID>
  </reference>
  <reference>
    <citation>Sohn DS, Kim WS, An KM, Song KJ, Lee JM, Mun YS. Comparative histomorphometric analysis of maxillary sinus augmentation with and without bone grafting in rabbit. Implant Dent. 2010 Jun;19(3):259-70. doi: 10.1097/ID.0b013e3181df1406.</citation>
    <PMID>20523182</PMID>
  </reference>
  <reference>
    <citation>Sohn DS, Heo JU, Kwak DH, Kim DE, Kim JM, Moon JW, Lee JH, Park IS. Bone regeneration in the maxillary sinus using an autologous fibrin-rich block with concentrated growth factors alone. Implant Dent. 2011 Oct;20(5):389-95. doi: 10.1097/ID.0b013e31822f7a70.</citation>
    <PMID>21881519</PMID>
  </reference>
  <reference>
    <citation>Rodella LF, Favero G, Boninsegna R, Buffoli B, Labanca M, Scari G, Sacco L, Batani T, Rezzani R. Growth factors, CD34 positive cells, and fibrin network analysis in concentrated growth factors fraction. Microsc Res Tech. 2011 Aug;74(8):772-7. doi: 10.1002/jemt.20968.</citation>
    <PMID>21780251</PMID>
  </reference>
  <reference>
    <citation>Nahlieli O. Dynamic implant valve approach for dental implant procedures. Chin J Dent Res. 2014;17(1):15-21.</citation>
    <PMID>25028685</PMID>
  </reference>
  <verification_date>December 2016</verification_date>
  <study_first_submitted>November 26, 2016</study_first_submitted>
  <study_first_submitted_qc>December 3, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 7, 2016</study_first_posted>
  <last_update_submitted>December 6, 2016</last_update_submitted>
  <last_update_submitted_qc>December 6, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">December 8, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Western Galilee Hospital-Nahariya</investigator_affiliation>
    <investigator_full_name>ruth angel dar</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>CGF</keyword>
  <keyword>sinus augmentation</keyword>
  <keyword>DIVA</keyword>
  <keyword>Platelet-Rich Plasma</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Alveolar Bone Loss</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02985645
org study id: 0153-16-NHR
nct id: NCT02985645
lead sponsor: 
has dmc: No
This study is intended to evaluate the efficiency of graftless maxillary sinus augmentation
      with concentrated growth factor (CGF) utilizing "dynamic implant valve approach" (DIVA)
      system.
Crestal bone deficiency in the posterior maxilla may present a therapeutic challenge when
      dental implants are required. Sufficient bone volume is necessary for the long term survival
      of the implant .

      The two most used surgical techniques are the crestal and the lateral window. The latter was
      first described by Tatum and subsequently, Boyene and James in 1980 . In the original
      technique, after fracturing the sinus floor, an implant was placed and submerged during the
      healing phase. The crestal osteotome technique is less invasive and was first described by
      Summers in 1994 . In this technique, a set of osteotomes is used to prepare the implant site,
      thereby allowing bone preservation.

      Since the sinus augmentation was describes, bone grafts have been the mainstay of treatment.
      Variable bone grafts, such as autografts, allografts, xenografts, alloplasts, or combinations
      of different graft materials, have been used widely with similar results . Nonetheless,
      successful bone augmentation in the maxillary sinus, without bone grafting, have been
      reported in human and animal studies.

      In 2011, Dong-Seok et al described sinus augmentation through a lateral window approach,
      using a fibrin rich block with concentrated growth factor (CGF). The researchers showed
      successful new bone formation in the sinus, with a success rate of 98% and no major
      complications .

      Graftless Sinus augmentation relies on bioactive mediators that stimulate cell proliferation,
      matrix remodeling, and angiogenesis. CGF is one of the latest developments in this field, and
      is produced by processing blood samples with a special centrifuge device. It contains several
      mediators - platelet-derived growth factor (PDGF), transforming growth factor-b1 (TGF-b1) and
      b2 (TGF-b2), fibroblast growth factor (FGF), vascular endothelial growth factor (VEGF), and
      insulin-like growth factor (IGF). Because CGF is a dense fibrin matrix, richer in growth
      factors than other preparations, it has proved to have a better regenerative capacity and
      versatility .

      As for the application of CGF, the introduction of the "dynamic implant valve approach"
      (DIVA), a minimally invasive approach procedure, enables the use of a closed bone
      augmentation technique. The implant was designed with an internal sealing screw that might
      serve as drug delivery system via its channel.

      In this study, a graftless maxillary sinus augmentation with CGF will be performed utilizing
      DIVA system, and the bone formation will be periodically measured using panoramic X-ray and
      cone beam computerized tomography (CBCT).

      In addition, in vitro cumulative release of selected growth factors of the CGF will be
      analyzed. The total quantity of growth factors will be checked using ELISA kits.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: bone formation after sinus augmentation
time frame: one year
description: during postoperative follow-up, bone formation in the maxillary sinus will be assessed by periodic imaging.
after one year the investigators expect to see complete implant integration into the bone formed in the maxillary sinus(e.g; the dental implant is completely covered by bone).
measure: Quantification of growth factors released from the CGF matrix in vitro
time frame: one year
description: ELISA test will be used to quantify the released growth factors, and the data will be compared to the factors released from regular bone material.
arm group label: Treatment
arm group type: Experimental
description: maxillary sinus augmentation with CGF
intervention type: Procedure
intervention name: maxillary sinus augmentation with CGF
description: Graftless maxillary sinus augmentation surgery with CGF application utilizing DIVA system
arm group label: Treatment
intervention type: Device
intervention name: "dynamic implant valve approach" - DIVA system
description: The DIVA system will be used to apply the CGF to the maxillary sinus.
arm group label: Treatment
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Samer Srouji, Prof.
role: Study Director
affiliation: Western Galilee Medical Center
last name: Ruth Angel-Dar, Dr.
phone: +972-4-9107076
email: rutiangel123@gmail.com
last name: Samer Srouji, Prof.
phone: +972-4-9107270
email: dr.samersrouji@gmail.com
facility: 
contact: 
country: Israel
citation: Del Fabbro M, Corbella S, Weinstein T, Ceresoli V, Taschieri S. Implant survival rates after osteotome-mediated maxillary sinus augmentation: a systematic review. Clin Implant Dent Relat Res. 2012 May;14 Suppl 1:e159-68. doi: 10.1111/j.1708-8208.2011.00399.x. Epub 2011 Nov 14.
PMID: 22082056
citation: Tatum H Jr. Maxillary and sinus implant reconstructions. Dent Clin North Am. 1986 Apr;30(2):207-29.
PMID: 3516738
citation: Summers RB. The osteotome technique: Part 3--Less invasive methods of elevating the sinus floor. Compendium. 1994 Jun;15(6):698, 700, 702-4 passim; quiz 710.
PMID: 7994726
citation: Danesh-Sani SA, Loomer PM, Wallace SS. A comprehensive clinical review of maxillary sinus floor elevation: anatomy, techniques, biomaterials and complications. Br J Oral Maxillofac Surg. 2016 Sep;54(7):724-30. doi: 10.1016/j.bjoms.2016.05.008. Epub 2016 May 25.
PMID: 27235382
citation: Falah M, Sohn DS, Srouji S. Graftless sinus augmentation with simultaneous dental implant placement: clinical results and biological perspectives. Int J Oral Maxillofac Surg. 2016 Sep;45(9):1147-53. doi: 10.1016/j.ijom.2016.05.006. Epub 2016 May 31.
PMID: 27256011
citation: Sohn DS, Kim WS, An KM, Song KJ, Lee JM, Mun YS. Comparative histomorphometric analysis of maxillary sinus augmentation with and without bone grafting in rabbit. Implant Dent. 2010 Jun;19(3):259-70. doi: 10.1097/ID.0b013e3181df1406.
PMID: 20523182
citation: Sohn DS, Heo JU, Kwak DH, Kim DE, Kim JM, Moon JW, Lee JH, Park IS. Bone regeneration in the maxillary sinus using an autologous fibrin-rich block with concentrated growth factors alone. Implant Dent. 2011 Oct;20(5):389-95. doi: 10.1097/ID.0b013e31822f7a70.
PMID: 21881519
citation: Rodella LF, Favero G, Boninsegna R, Buffoli B, Labanca M, Scari G, Sacco L, Batani T, Rezzani R. Growth factors, CD34 positive cells, and fibrin network analysis in concentrated growth factors fraction. Microsc Res Tech. 2011 Aug;74(8):772-7. doi: 10.1002/jemt.20968.
PMID: 21780251
citation: Nahlieli O. Dynamic implant valve approach for dental implant procedures. Chin J Dent Res. 2014;17(1):15-21.
PMID: 25028685
responsible party type: Principal Investigator
investigator affiliation: Western Galilee Hospital-Nahariya
investigator full name: ruth angel dar
investigator title: Principal Investigator
mesh term: Alveolar Bone Loss